The role of photobiomodulation therapy in the care of cancer patients: review of the literature (PDF Download Available)
See all >39 References
14.62Hasselt University22.27Jessa Hospital+ 5Show more authorsAbstractPhotobiomodulation therapy is based on the application of visible and/or (near-)infrared light on the target tissue. We performed a review of 34 articles on the use of photobiomodulation therapy in the management of cancer related lymphoedema, oral mucositis, radiodermatitis, chemotherapy-induced peripheral neuropathy, osteonecrosis of the jaw, and xerostomia/hyposalivation. The findings suggest that photobiomodulation therapy is a promising option for the management of these cancer therapy-related side effects.Discover the world's research14+ million members100+ million publications700k+ research projects
VOLUME11DECEMBER2017364SUMMARYPhotobiomodulation therapy is based on the application of visible and/or (near-)infrared light on the target tissue. We performed a review of 34 articles on the use of photobiomodulation therapy in the management of cancer related lymphoedema, oral mucositis, radiodermatitis, chemotherapy-induced peripheral neuro-pathy, osteonecrosis of the jaw, and xerostomia/hyposalivation. The ?ndings suggest that photobiomodula-tion therapy is a promising option for the management of these cancer therapy-related side effects. (BELG J MED ONCOL 2017;11(8):364-374)1Faculty of Medicine & Life Sciences, Hasselt University, Hasselt, Belgium, 2Limburg Oncology Centre, Hasselt, Belgium, 3Division of Medical Oncology, Jessa Hospital, Hasselt, Belgium. Please send all correspondence to: J. Robijns, MSc, Faculty of Medicine & Life Sciences, Hasselt University, Martelarenlaan 42, 3500 Hasselt, Belgium, tel: +32 11 33 72 29, email: Jolien.robijns@uhasselt.be. Con?ict of interest: This study is par t of the Limburg Clinical Research Program (LCRP) UHasselt-ZOL-Jessa, suppor ted by the foundation Limburg Sterk Merk, province of Limburg, Flemish government, Hasselt Universit y, Ziekenhuis Oost-Limburg and Jessa Hospital. Additionally, this research is suppor ted by the foundations Limburgs Kankerfonds, Kom op Tegen Kanker and ASA srl.Keywords: cancer, low-level laser therapy, oncology, photobiomodulation therapy, side effects, supportive care.INTRODUCTIONCancer therapy ranging from surgery, chemotherapy (CTx), radiotherapy (RT) to targeted systemic therapies (e.g. hor-mone- and/or immunotherapy) can cause serious side effects. The severity of the side effects depends on the cancer type and site, the therapy characteristics, and the individual pa-tient susceptibility. The patients’ quality of life can seriously be affected by these side effects and therefore effective sup-portive care strategies are necessary.1 The use of photobio-modulation therapy (PBMT), also known as low-level laser therapy (LLLT), was introduced in 1967 by Mester et al.2 It’s based on the application of visible and /or (near-)infrared light by laser diodes (LDs) and/or light-emitting diodes (LEDs) on target tissue.3 Several studies have demonstrated that PBMT is able to stimulate the wound healing process, reduce in-flammation, and relieve pain.4 For the last twenty years, the use of PBMT for the management of cancer therapy-relat-ed side effects has been investigated in several clinical trials. However, for a lot of clinicians this new and emerging thera-peutic option is still unknown.5 The aim of this review was to summarise all the available clinical trials that examined the applicability of PBMT in the domain of cancer related lymph-oedema (CRL), oral mucositis (OM), radiodermatitis (RD), chemotherapy-induced peripheral neuropathy (CIPN), os-teonecrosis of the jaw (ONJ), and xerostomia/hyposalivation. PBMT – CELLULAR AND TISSUE MECHANISM
The basic mechanism behind PBMT is quite complex and is still not completely clear. Several studies demonstrated that the light is absorbed by endogenous chromophores in the target cells. The main chromophore is cytochrome c ox-J. Robijns, MSc1,2, S. Censabella, PhD3, P. Bulens, MD2,3, A. Maes, MD2,3, L. Noé, MD2,3, M. Brosens, MD2,3,
L. Van den Bergh, MD, PhD2,3, S. Claes3, J. Mebis, MD, PhD1-3The role of photobiomodulation therapy in the care of cancer patients: review of the literature
VOLUME11DECEMBER20178REVIEW ONCOLOGY 365idase (CCO), located in the mitochondrial membrane. The absorbed light energy stimulates the electron transport chain in the mitochondria leading to an increased production of adenosine triphosphate (ATP). An increase in ATP will im-prove the cellular metabolism, leading to improved cellular functions.4 Additionally, the nitric oxide (NO) production can be regulated by PBMT. NO causes vasodilatation, which will improve the transport of oxygen and immune cells in-to the tissue leading to enhanced cell repair.4 Finally, PBMT can stimulate the production of a low level of reactive oxygen species (ROS). A low concentration of ROS can activate sev-eral transcription factors, leading to upregulation of various genes. These will generate proteins such as growth factors and inflammatory mediators that are involved in the wound healing process.4 Evidence of in vitro and in vivo studies show that PBMT is able to influence each phase of the wound healing process by enhancing phagocytosis and angiogenesis, by downreg-ulating inflammatory mediators, by increasing the prolifera-tion of keratinocytes and fibroblasts, and by stimulating the collagen synthesis.6,7 PBMT IN THE SUPPORTIVE CARE OF CANCER PATIENTS Cancer-related lymphoedema (CRL)Lymphoedema is a common side-effect in patients treated for breast cancer (BC) and head and neck cancer (HNC). In approximately 20% of BC patients, lymphoedema can de-velop in the upper extremity after BC treatment. Patients with breast cancer-related lymphoedema (BCRL) have to cope with pain and a diminished arm mobility leading to decreased daily functional activity.8 Lymphoedema in HNC patients can develop externally, on the face and/or neck, or internally at the pharynx or larynx. A study by Deng et al. with 81 HNC patients, showed that 75 % of the patients de-veloped CRL (10% external, 39% internal, and 51% both types). External CRL may affect the patient’s body image, while internal CRL may cause breathing, swallowing, and speaking problems.9The treatment of CRL is focused on preventing disease pro-gression and reducing the symptoms. Complete deconges-tive therapy (CDT) is the main treatment option for CRL.10 PBMT FOR THE MANAGEMENT OF CRLThe effectiveness of PBMT for the management of BCRL has already been demonstrated in several studies and in 2006 it was accepted as treatment option by the Food and Drug Ad-ministration (FDA).11 The beneficial effect of PBMT on BCRL is explained by the fact that it is able to stimulate the lymph flow and increase the number of lymph vessels. In addition, PBMT can also prevent the formation of fibrotic tissue.11 A meta-analysis of nine studies by Smoot et al. demonstrated moderate evidence for the effectiveness of LD-PBMT in the re-duction of arm swelling and pain in women with BCRL (Table 1). Additionally, these studies showed that the combination of PBMT with CDT is more effective in reducing the arm volume than with CDT alone.11 A recent randomised, placebo-con-trolled clinical trial (RCT) with 40 BC patients confirmed the results of the meta-analysis.12 Up to now, there was only one case-control study that showed a beneficial effect of LD-PBMT in the management of CRL in HNC patients.13A task force consisting of an international multidisciplinary panel of clinicians and researchers with expertise in the area of supportive care in cancer and/or the use of PBMT, devel-oped guidelines for the management of complications related to cancer therapy. They suggested using a LED- or LD-PBMT device (wavelength 750-830 nm, power density 20– 80 mW/cm2, fluence 3 J/cm2) two to three times a week to treat CRL until symptoms improve. They suggested applying it on the edematous area and the regional lymphatic chain.1Oral mucositis (OM)OM occurs in 20-40% of patients undergoing conventional CTx and in almost all patients undergoing RT for HNC. It is characterised by erythematous mucosal changes, which can develop into ulceration of the oral mucosa. OM can serious-ly affect the patient’s quality of life, as it can be very painful and lead to malnutrition. In severe cases of OM, parenter-al nutrition or eventually hospitalisation is necessary to pre-vent underfeeding.14The guidelines of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) recommend the use of cryotherapy, oral care protocols, pain medication, and anti-inflammatory mouth-wash to prevent and manage OM.14PBMT IN THE PREVENTION AND MANAGEMENT OF OMThe use of PBMT for the prevention and management in OM has already been extensively investigated (Table 2). A meta-analysis of eleven RCTs in HNC patients showed that LD-PBMT reduced the OM incidence, severity, duration, and the associated pain.15 Oberoi et al. performed another systematic review with meta-analysis of eighteen RCTs in which they showed that prophylactic use of LD-PBMT re-duced severe OM and its associated pain in patients treated for HNC or undergoing hematopoietic stem cell transplanta-tion (HSC T).16 In 2014, the MASCC/ISOO panel developed clinical practice guidelines in which they included the use of PBMT in the prevention and management of OM based
VOLUME11DECEMBER2017366TABL E 1.
Summary of clinical studies investigating the use of PBMT for the management of CRL. First au-thor (ref.)Year Publica-tion typeStudy type Sample size + can-cer typeTreatment groupsPBMT device Wave-length (nm)Power (mW)Energy density (J/cm2)Laser scheduleEvaluation sched-uleResultsPiller11 1998 Full articleSingle group10 BC LD-PBMT S Space Mid M3-UP LDScanning head: 632.8 IR lasers: 904 (x2)10-14 NA 16 sessions over 10 weeksPre-treatment During treatment: biweekly Post-treatment: ?nal treatment, 1, 3, 6, 30–36 months42% reduction in arm volume after PBMT. The arm tissue (except the upper arm) softened. Subjective symptoms improved (e.g. pain, cramps, heaviness, mobility).Carati11 2003 Full articleDouble-blind, single crossover RCT64 BC - Sham laser and
1 cycle of LD-PBMT- 2
cycles of LD-PBMTDirect con-tact: Rian Corp LTU 904H LD904 5 NA 3×/week for 3 two cycles (18 ses-sions) 8-weeks between -cycle washout periodPre-treatment Post-treatment: ?nal treatment and 4, 8, 12 weeks for each cyclePBMT reduced effectively the arm volume, extracellular ?uid and tissue stiffness in 33% of the patients.Kaviani11 2006 Full articleDouble-blinded RCT11 BC -LD-PBMT- Sham laserNoncontact mode ap-plied 1 cm
Mustang-024
Ga-As LD890 10 1.5 3×/week × 3 weeks 2 cycles with an 8 week inter-cycle washout period (18 sessions)Pre-treatment Post-treatment cycle 1: Immediately (?nal treatment) and week 9 Post-treatment cycle 2: weeks 18 and 22In both groups the arm circum-ference decreased, but no signi?cant difference between the groups.
Maiya11 2008 Full articleCycled RCT20 BC - LD-PBMT + UE exercise - UE
exer-cise + CG-Thor DD L He-Ne laser
-EC Laser T LD632.8 850NA NA D 10 days (10 sessions)Post-treatment: immediately(Final treatment)Signi?cantly higher reduction in arm volume and pain score in PBMT group. Kozano-glu112009 Full articleRCT; blinded, alternating allocation50 BC - LD-PBMT + educ - IC + educElectronica Pagani IR27/4 Ga-As LD904 NA 1.5 3×/week × 4 weeks (12 ses-sions) 4 weeks (20 sessions)Pre-treatment Post-treatment: immediately , 3, 6, , and 12 monthsArm circumference and pain score reduced in both groups, but the long-term results were better in the PBMT group.Lau11 2009 Full articleSingle-blinded RCT21 BC
- LD-PBMT + educ - Waitlist
+ educScanning 50 cm above
Comby 3 Terza Serie, Model D LD808 905x2NA 2 3×/week × 4 weeks (12 sessions)Pre-treatment Post-treatment: immediatelyNo signi?cant difference in arm volume reductions between the two groups.Dirican11 2011 Full articleSingle group pretest-posttest17 BC LD-PBMT + CB/CGDirect contact Rian Corp LTU 904H LD904 5 NA 3×/ two 3-week
8-week hia-tus between cycles (18 sessions)Pre-treatment Post-treatment immediately for each cycleCombination of PBMT with CB showed bene?ts in the reduc-tion of arm volume, pain and scar mobility. Omar11 2011 Full articleDouble-blind RCT with placebo group50 BC - LD-PBMT + exer-cise + educ + CG - Sham laser + exercise + educ + CGDirect con- Rian-Corp Ga-As LD904 5 1.5 3×/week × 12 weeks (36 ses-sions)Pre-treatment During treatment: weeks 4 and 8 Post-treatment: immediately and 4 weeksSigni?cant reduction in arm volume. Signi?cant increase in shoulder mobility and handgrip strength in 93% of patients.Ridner11 2013 Full articleRCT 46 BC - LD-PBMT- MLD- MLD
+ LD-PBMTAll re-ceived CBDirect con-tact: Rian Corp LTU 904H LD904 5 NA Average number of sessions: -PBMT: 10 -MLD: 8 -MLD + PBMT: 10Pre-treatment Post-treatment: immediately Arm volume reduced in all groups, but no signi?cant differ-ence between the groups. No differences in quality of life. Skin quality improved in all groups. Lee13 2013 Full articleCase control study1 HNC - LD-PBMT - 104
Diode Cluster Probe (lymphatic pathways)- 904-LTU
(?brotic areas)NA 5-10 1.5 and 3Daily over 3 weeksPre-treatment, weekly during PBMT and 3 month after the end of PBMTSigni?cant reduction in oedema and improvement in swallowing.Storz12 2016 Full articleDouble-blind RCT with placebo group40 BC - LD-PBMT group - Sham laser groupCluster la-ser device, non-contact mode: “TIME-LAS Vital”980 640 4.89 2x/week x 4 weeksPre-treatment Post-treatment: immediately, 1-3 months50% reduction in median pain score. Increase in mean quality of life and grip strength in PBMT group. No statistically signi?cant difference between the groups.Partially adapted from Robijns et al. (2017)5Abbreviations: BC, HNC, head and neck c CRL, cancer-related lymph RCT, randomised control LD,
PBMT, photobiomodula MLD, manual lymphat CB, compression bandaging; educ, CG, compression garme IC, intermittent comp NA, n ref, UE, upper extremity.
VOLUME11OCTOBER20178367REVIEW ONCOLOGYon a meta-analysis performed by Migliorati et al.17 Following these guidelines, PBMT is recommended for the prevention of OM in patients receiving high-dose CTx in case of HSCT. In addition, they suggested using PBMT for the prevention of OM in HNC patients undergoing RT without concomitant CTx.14,17 The European Society for Medical Oncology (ESMO) and the National Comprehensive Cancer Network (NCCN) also recommend the use of LD-PBMT in patients receiving high-dose CTx or chemoradiotherapy (CRT) before HSCT.18,19The guidelines of Zecha et al. proposed to use PBMT both in a preventive and therapeutic manner (wavelength 630-830 nm, power density 20-80mW; energy density 2–4 J/cm2). The prophylactic use of PBMT can start before or on the first day of CTx/ RT and continue during all days of the therapy on each site of the mucosal surface that is at risk. Once OM has developed PBMT is recommended two to three times a week up to daily until the symptoms improve.1Radiodermatitis (RD)RD affects up to 95% of the patients undergoing RT. RD is an inflammatory skin reaction that is characterised by red rash-es, dry desquamation and in some cases moist desquamation. The severity of the skin reactions depends on different thera-py- and patient-related factors. RD is a distressing and painful side effect of RT, which can lead to problems in the patients’ daily life (e.g. washing practices, getting dressed, household activities, hobbies). Rarely, the skin reactions become too se-vere, leading to interruption of RT for a short period of time.20 Existing treatment options for RD include different topical agents such as moisturising creams/gels and wound dress-ings. The MASCC panel developed clinical practice guide-lines for the prevention and treatment of RD. However, the available evidence is still to weak to support a general con-sensus on the management of RD.21 PBMT FOR THE PREVENTION AND MANAGEMENT OF RD The research on the use of PBMT for the prevention and man-agement of RD in cancer patients is limited (Table 3). Schindl et al. introduced it in the late 1990’s, by perform-ing a case report study in which they treated three breast patients with RT-induced skin ulcers after mastectomy. Re-TABL E 2 .
Summar y of reviews with meta-analysis investigating the use of PBMT for the prevention and management of OM in cancer patients.First author (ref.)Year
Publication typeType + num-ber of stud-ies included Sam-ple sizeWavelength (nm)Power (mW)Energy density (J/cm2)Laser
scheduleResultsBjordal15 2011 Systematic
review with meta-analysis 11 placebo-controlled RCTs415 -
Red (633–685)-
Infrared (780–830)-Red (10-60) -Infrared (50-100)1-6 J/pointMinimum
3 sessions/weekReduced OM prevalence,
severity, duration, and associated pain.Migliorati17 2012 Systematic
review with meta-analysis 24 clinical trials NA
10-500 2-70 NA Recommenda-tion: -
Prevention of OM in adult pa-tients receiving HSCT (650 nm, 40 mW, and 2 J/cm2).Suggestion: -
Prevention of OM in HNC pa-tients
under-going RT with-out CTx(632.8 nm).Oberoi16 2014 Systematic review with meta-analysis 18 RCTs and quasi-RCTs 1144 632.8-780 10-100 1.5-6.3 5 sessions/week - dailyProphylactic PBMT reduced severe OM and pain in patients with cancer and HSCT recipients.Partially adapted from Robijns et al. (2017)5Abbreviations: OM, oral mucosi CTx, chemothe HNC, head and neck cancer; HSCT, hematopoietic stem cell
RCT, randomi NA, not a ref, r PBMT, photobiomodulation therapy.
VOLUME11DECEMBER2017368sults showed that LD-PBMT was able to improve the wound healing process of the skin ulcers.22 Furthermore, there were two studies that investigated the use of LED-PBMT for the prevention of RD.23,24 A study by Deland et al. showed that LED treatments reduced the incidence of RD in breast can-cer patients.23 In contrast, Fife et al. was not able to replicate these results in a RCT.24 A possible explanation for the dif-ferent results is the use of different treatment and assessment parameters in both studies. A more recent study by our re-search group showed that LD-PBMT is an effective treatment for acute RD in breast cancer patients. PBMT prevented the aggravation of acute RD and reduced the impact of it on the patients’ quality of life.25 Zecha et al. suggested using LED- or LD-PBMT (wavelength 630–680 nm; power density 20-150mW/cm2; energy den-sity 2–4 J/cm2) in a prophylactic (daily from the first day of RT) or a therapeutic regime (minimum three times a week) on the cutaneous surfaces of the irradiated area (Figure 1).1Chemotherapy-induced peripheral neuropathy (CIPN)Neurotoxic chemotherapeutic substances (e.g. platinum agents, taxanes, vinca alkaloids, thalidomide, and bortezo-mib) can lead to chemotherapy-induced peripheral neurop-athy (CIPN). It affects approximately 68.1% of the patients when measured in the first month after CTx, 60.0% at three?months and 30.0% at six?months or more.26 The risk for developing CIPN is determined by the type of CTx agents, the administration time, and the cumulative dose. Most pa-tients with CIPN develop sensory dysfunctions. Some-times motor dysfunctions such as muscle weakness and/or autonomic neuropathy can also establish. The underlying mechanism causing CIPN is still unclear but is known that chemotherapeutic agents can damage the peripheral and/or central nerve system, affecting the communication in the nerve tracts. Patients with CIPN have to cope with function-al problems during their daily life. In severe cases of CIPN, CTx dose reductions, changes in the CTx dosing or even a CTx termination need to be performed, leading to dimin-ished overall survival.27To date, there is still no effective treatment for CIPN. Current-ly, the main focus in the management of CIPN is reducing the symptoms by medication and/or physical therapy. PBMT AND CIPNThe use of PBMT for the management of CIPN has only been investigated in three clinical trials (Tab le 4). Yamada et al. in-vestigated the use of LD-PBMT in a single-arm, prospective study with 34 female BC patients undergoing taxane-based FIGURE 1. The application of PBMT to an irradiated breast of a breast cancer patient to treat acute radiodermatitis.
VOLUME11DECEMBER20178369CTx. The patients evaluated the effectiveness of the treat-ment by using a 10-point scale Brief Pain Index (BPI) ques-tionnaire before and after each laser session. At the end of the trial the BPI score of the patients ameliorated with an av-erage of four points.28 In a more recent, prospective cohort study with pre- and post-intervention design by Hsieh et al., seventeen patients with gastrointestinal cancer were treated with LD-PBMT. Results revealed that after twelve sessions of PBMT, the patients’ neurotoxicity symptoms were dimin-ished and moreover their cold and mechanical allodynia was resolved.29 Argenta et al. enrolled 70 patients treated with CTx for cancer of different aetiology in a randomised-control, crossover trial to determine if LD-PBMT (eighteen sessions) with or without physiotherapy reduced the symptoms of CIPN compared to a sham treatment. This study demonstrat-ed that LD-PBMT could reduce the CIPN associated symp-toms effectively.30 These findings indicate that LD-PBMT might be an effective therapeutic option for CIPN. However, it was not taken up in the guidelines developed by Zecha et al.1 Our research unit is now performing a RCT investigating the effectiveness of PBMT in the prevention of CIPN in breast cancer patients undergoing taxane treatment.Osteonecrosis of the jaw (ONJ)Patients with bone metastases or multiple myeloma are gener-ally treated with bisphosphonates (BP) or denosumab. These treatments inhibit bone turnover by inducing osteoclastic apoptosis and inhibiting the osteoblast-mediated osteoclastic activity. A serious side effect is osteonecrosis of the jaw (ONJ), which occurs in 0.8% to 12% of the patients.31 ONJ is a serious and painful side effect.32 Each case of ONJ needs to be evaluat-ed and treated individually. The American Association of Oral and Maxillofacial Surgeons (AAOMS) developed guidelines based on the stage of the disease, good oral hygiene, phar-macological therapy (e.g. antibiotics, pain medication) and, in case of exposed bone, surgical removal is recommended.32 PBMT FOR THE TREATMENT OF ONJPBMT is known to have bio stimulatory effects that can up-regulate the production and mineralisation of the bone.33 Additionally, PBMT also has anti-bacterial effects and is proangiogenic.34A recent review by Latifyan et al., summarised the results of seven clinical trials that investigated the efficiency of PB-MT for the treatment of ONJ (Table 5 ).35 They showed that REVIEW ONCOLOGYTABLE 3. Summary of clinical studies investigating the use of PBMT for the management of RD in cancer patients.First author (ref.)Year Publica-tion typeStudy typeSam-ple sizePBMT deviceWave-length (nm)Pow-er (mW)Energy density (J/cm2)Laser scheduleEvalu-ation scheduleAssess-ment scaleResultsSchindl22 1999 Full article Case report 3 HeNe LD632.8 30 30 3 times/week until wound closureWeekly and at 36 months follow-upNA Accelerated wound heal-ing.DeLand23 2007 Full article Prospective study with a retrospec-tive control group47 LED 590 NA 0.15 Daily after each RT ses-sionWeekly NCI CTC Signi?- cantly reduced incidence of RD.Fife24 2010 Full article Prospective, double-blind RCT with a placebo group33 LED 590 NA NA Daily before and after each RT ses-sion + 7 ad-ditional daily treatments after the end of RTBaseline, weekly during RT and 2-6 weeks after the end of RTNCI CTC No signi?cant effects.Censa-bella252016 Full article Prospective quasi-ex-perimental study with control and PBMT group79 LD 808-905 60 4 2 times/week after the RT session start-ing at fraction 20 of RTBaseline, fraction 20 of RT and at the end of RTRTOG Signi?cantly reduced incidence of RD grade.Partially adapted from Robijns et al. (2017)5Abbreviations: RD, radiodermatitis; HeNe, Helium Ne LED, Light Emitting D NA, not availa RT, radiother NCI CTC, National Cancer Institute Common Toxicity Criter RTOG, Radiation Therapy Oncology G RD, radiode ref, ref LD, PBMT, photob RCT, randomised controlled trial.
VOLUME11DECEMBER2017370the overall response rate was 55% in PBMT treated patients, which was significantly higher than in the control group (30%). The studies revealed that PBMT was able to improve ONJ by improving the healing process of the lesions and re-ducing the accompanied pain.35 Zecha
et al. also formulated some clinical guidelines on a therapeutic base in which they recommended to use LD- or LED-PBMT two to three times a week up to daily by using an extra- (wavelength 750-830 power density 20-80mW; energy density 6 J/cm2) or intra-oral device (wavelength 630–680; power density 20-200mW; energy density 6 J/cm2) on five or more points (1 cm apart) along lingual and buccal as-pects of the maxilla and /or mandible depending on site and size of region affected.1Hyposalivation and xerostomia RT to the head and neck region destroys the function of the salivary glands leading to hyposalivation (i.e. reduced saliva production), which is accompanied by xerostomia (i.e. sub-jective oral dryness). Other cancer therapies (e.g. CTx, im-munotherapy, radioactive iodine treatment and total body irradiation/HSCT) can also induce hyposalivation and xero-stomia, although to a minor severity. Hyposalivation increas-es the risk of oral infections and can lead to teeth damage, oral mucosal discomfort, pain, and eating problems. Con-sequently, patients with hyposalivation cannot fully per-form their daily activities and have diminished general well being.36Intensity-modulated radiation therapy (IMRT) has the great-est potential to spare the salivary gland tissue and prevent the development of hyposalivation. Furthermore, good oral hygiene and dental care is recommended before, during, and after treatment. PBMT FOR THE TREATMENT OF HYPOSALIVATION AND XEROSTOMIATo date, there were only a small number of studies investigat-ing the use PBMT for the management of hyposalivation (Ta-ble 6). Cowen et al. performed a placebo-controlled RCT with 30 patients that underwent HSCT to investigate the efficiency of LD-PBMT. Xerostomia and the ability to swallow improved in the patients that were treated with LD-PBMT.37 Simoes et al. reported on a prospective study with two patient groups of which one group was treated once a week with LD-PBMT TABLE 4. Summary of clinical studies investigating the use of PBMT for the management of CIPN in cancer patients.First
author (ref.)Year Publi-cation typeStudy typeSample sizeTreatment PBMT deviceWave-length (nm)Power (mW)Energy density (J/cm2)Laser sched-uleEvalu-ation scheduleAssess-ment scaleResultsYamada28 2010 Abstract Single
pretest-post test34 BC LD-PBMT GaAlAs LD 830 NA NA NA Before and after irradiationBPI score BPI score decreased with an average of 4. Argenta30 2016 Full ar-ticleDouble-blind, placebo-con-trolled, RC cross-over trial68 (≠aetiol-ogy) - LD-PBMT- LD-PBMT/PT-Sham laserClass IV therapeu-tic laser (Eltech K1200)800-970NA NA 3x/week for 6 weeksAt the ?rst laser session and at 4, 8, and 16 weeks following initiation of treatmentmTNS scoreSigni?cant reduction in mTNS score at all time points in the PBMT group.Hsieh29 2016 Full ar-ticleProspec-tive, single-arm study17 GIC -LD-PBMT GaAlAs LD
780 50 7.5 12 ses-sionsBefore the ?rst and after the last ses-sionNeuro-toxicity symptom evaluationNeurotoxic-ity symp-toms (pain, cold- and mechanical allodynia) signi?cantly improved.Partially adapted from Robijns et al. (2017)5Abbreviations: BC, GIC, gastro-intestina CIPN, chemotherapy-induced peripheral neuro PBMT, photobiomodulation therapy; BPI, Brief Pain Index; NA, ref, LD, RC randomised
mTNS, modi?ed Total Neuropathy Score.
VOLUME11DECEMBER20178371TABL E 5. Summary of clinical studies investigating the use of PBMT for the management of ONJ in breast cancer patients.First author (ref.)Year Publi-cation typeStudy typeSample sizeTreatment PBMT deviceWave-length (nm)Power (mW)Energy density (J/cm2)Laser scheduleEvaluation scheduleResultsAngiero35 2009 Full articleThree
pretest-posttest49 - LD-PBMT (n=10)- Surgical intervention (n=20)- Conserva-tive therapy (n=19)Er:YAG laser880 NA 27-54 3 applica-tions12—80 months follow up periodCR=6; PR=4Scoletta35
2010 Full articleSingle
pretest-posttest20 LD-PBMT Pulsed LD904 7 28.4 10 ses-sions over a period of 20 days1h before the laser procedure and 28 days afterSigni?cant de-crease in pain score, clinical size, oedema, and pres-ence of pus and ?stulas.Atalay35
2011 Full articleRCT 20 - Laser
surgery + LD-PBMT (n=10)- Conven-tional surgery (n=10)Nd:YAG laser950 250 6.25 5 sessions over a period of 10 daysEvery other day for the ?rst 10 days and monthly for the next 6 monthsNo signi?cant dif-ference between the groups.Romeo35
2011 Full articleSingle
pretest-posttest7 LD-PBMT Double LD650 904–910100- 500NA Every 3 days for 2 weeksTwice before each PBMT cycle, once before the initial laser application and 3 days after the last laser applica-tionSigni?cant dif-ference in NRS score.Vescovi 35 2012 Full articleFive
pretest-posttest190 - Medical therapy- Medical therapy + LD-PBMT- Surgery- Surgery+ LD-PBMT- Er:YAG
laser surgeryNd:YAG Laser1064 NA 14.37 Weekly during 2 monthsNA - LD-PBMT + sur-gery: improved healing in 82.3% of the sites and complete healing in 70.6% of the sites - LD-PBMT + medi-cation: improve-ment in 64.3% of the sites and complete healing in 21.4% of the sitesMartins35 2012 Full articleThree
pretest-posttest22 - Clinical
pro-tocol (n=3)- Surgical
pro-tocol (n=5)- PRP+LD-PB-MT (n=14)InGaAlP LD660 40 6 Daily until mucosal healingFollowed until muco-sal wound healing was clinically observed or weekly dur-ing the ?rst monthCR=12; PR=2Altay35 2014 Full articleSingle
pretest-posttest11 LD-PBMT GaAlAs LD808 500 5 Five ses-sion on post- op-erative day 1, 3, 5, 7, and 10Before the start of laser and follow-up (6-25 months)CR=4; PR=7Partially adapted from Robijns et al. (2017)5Abbreviations: ONJ, osteonecrosis of the jaw; PBMT, photobiomodulation therapy; PRP, platelet- LD; CR, complete PR, partia NRS, numerical r NA, n ref, LD, laser diode.REVIEW ONCOLOGY
VOLUME11DECEMBER2017372and the other one three times a week. Results showed that xerostomia improved in both groups, although it was better in the group that received LD-PBMT three times a week.38 In a double-blind RCT by Arbabi-Kalati et al., they demon-strated that LD-PBMT can reduce the incidence of severe xerostomia.39 Oton-leite et al. enrolled 60 HNC patients re-ceiving RT in a RCT investigating the effect of LD-PBMT on oral complications. They were able to demonstrate that the salivary flow of the patients treated with LD-PBMT signifi-cantly improved.40 A recent study by Saleh et al. in HNC pa-tients, found no significant improvement of hyposalivation and xerostomia after LD-PBMT treatment. This might be due to fibrosis and acinar atrophy of the glandular tissue.41The guidelines by Zecha et al. suggested the use of an extra- (wavelength 750-830 nm; power density 20-80mW; ener-gy density 3 J/cm2) and/or intra-oral LED/LD-PBMT device (wavelength 630-680 power density 20-150mW; energy density 3 J/cm2) starting the first day of RT and continuing daily during RT for the prevention of xerostomia and hypos-alivation by targeting the major and minor salivary glands.1 CONCLUSIONBased on evidence collected in this review, PBMT has the po-tential to become a new preventive and therapeutic option for a broad range of acute and chronic side effects associated with cancer therapy. Especially for the prevention and man-agement of OM, the use of PBMT has already been accepted in the general treatment guidelines developed by the MAS-TABL E 6. Summary of clinical studies investigating the use of PBMT for the management of xerostomia/hyposalvation in cancer patients.First author (ref.)Year Publica-tion typeStudy typeSample size Treatment PBMT deviceWave-length (nm)Power (mW)Energy density (J/cm2)Laser scheduleEvaluation scheduleResultsCowen37 1997 Full article Double-blind, placebo-controlled RCT30 -LD-PBMT -Sham laserHeNe LD 632.8 60 1.5 5 consecu-tive days before the HSCTDaily starting ?rst day of HSCT until day 20 post-HSCTXerostomia and ability to swallow improved.Simoes38 2010 Full article
Prospec-tive, two-group study22 - LD-PBMT 3x/week- LD-PBMT 1x/weekAlGaIP LD 660 40 6 Started within the ?rst 2 weeks of RT until complete healing of OMFirst and last session of PBMTXerostomia improved in both groups, but was better in the group 3x/week.Arbabi-Kalati392013 Full article Double-blind ran-domized trial48 -LD-PBMT-Sham laserLD 630 30 5 Before each CTx ses-sionBefore the CTx and ev-ery 2 weeks until the end of CTxSevere xerostomia (grade 3) was pre-vented.Oton-Leite402013 Full article Double-blind, placebo-controlled RCT60 -LD-PBMT-Sham laserInGaAlP diode laser 685 35 2 A week before RT and daily for 5 consecu-tive days before each session of RT until the end of RT1 week after starting RT, at the 15th RT session and at the ?nale RT sessionSigni?cantly higher SFR in the PBMT group.Saleh41 2014 Full article Double-blind, placebo-controlled RCT23 -LD-PBMT-Sham-laserGaAlAs diode 830
100 71 2x/week for 6 weeksBefore the start of PBMT, at the 6th session of PBMT and at the last ses-sion (12)No sig-ni?cant increase of SFR or decrease of xerostomia.Abbreviations: CTx, chemotherapy; RT, LD, PBMT, photobiomodulat HSCT, hematopoietic stem cell trans OM, oral m SFR, salivary ?ow r ref, RCT, randomised controlled trial.
VOLUME11DECEMBER20178373CC and ESMO. For the other applications, more RCTs with larger patient populations are necessary to confirm the prom-ising results of the current trials. In the future trials more attention needs to be paid towards the identification of the most effective PBMT parameters for each individual medical condition. Finally, more research is needed to evaluate any potential side effects of PBMT that might influence tumour behaviour and/or proliferation. REFERENCES 1. Zecha JA, Raber-Dur lacher JE, Nair RG, et al. Low-level laser the rapy/photo-biomodulation in the management of side effects of chemoradiation the rapy in head and neck canc er: par t 2: proposed applications and tre atment proto cols. Suppor t Care Can cer. 2016;24(6):2793-805.2. Mester E. [Th e use of the laser beam in t herapy]. Or v Hetil. 1966;107(22):1012-6.3. WALT/NA ALT. Photobiomodulation: ma instream medicine and beyo nd. WALT Biennial Congress and NAALT Annual Conference, Arlington Virginia USA (Sep-te m be r 2014 ).
20 14.4. Huang Y Y, Sharma SK, Car roll J, et al. Biphasic dose res ponse in low level light therapy - an update. Dose Respo nse. 2011;9(4):602-18.5. Robijns J, Censabella S, Bulens P, et al. The use of low-leve l light therapy in suppor tive care for patients with breast cancer: review of the literature. Lasers Me d Sci .
20 17;3 2(1):22 9 - 42 .6. Hawkins D, Abrahamse H. Effect of multiple exp osures of low-l evel laser ther-apy on the cellular res ponses of wo unded hu man skin ?broblasts. Photomed Laser Surg. ):705-14.7. Posten W, Wrone DA, Dover JS, et al. Low-level laser therapy for wound h eal-ing: mecha nism and ef ?cacy. Derm atol Surg. 200 5;31(3):334-40.8. DiSipio T, Rye S, Newm an B, et al. Incid ence of unilateral ar m lymphoedema after bre ast cancer: a systematic review and meta-anal ysis. Lan cet Oncol. 2013 ;14(6): 50 0 -15.9. Deng J, Ridne r SH, Dietri ch MS, et al. Prevalence of secondar y lymph ede-ma in patients with hea d and neck c ancer. J Pain Symptom Manag e. ):244 -52.10.
Hwang JM, Hwang J H, Kim TW, et al. Long-term effec ts of complex d econ-gestive th erapy in breast canc er patients with arm l ymphe dema after axillary di s-section. Ann Rehabil Med. 2013;37(5):690-7.11. Smoot B, Chiavola-Larson L, Lee J, et al. Effec t of low-level las er therapy on pain and swelling in wo men with b reast cancer-related lym phedem a: a systemat-ic review an d meta-analysis. J Canc er Sur viv. 2015;9(2):287-304.12. Storz MA, Gronwa ld B, Gottsc hling S, et al. Photobiomodu lation Therapy in breast cancer-related lymphedema: a randomized placebo-controlled trial. Pho-todermatol Photoimmunol Photomed. 2017;33(1):32-40.13. Lee N, Wigg J, Carroll J. The use of low level light therapy in the t reatment of head and neck oedema. Journal of Lymphoedema. 2013;8(1):35-42.14. Lalla RV, Bowen J, Barasch A, et a l. MASCC/ISOO clinical p ractice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2014;120(1 0) :145 3 -6 1.15. Bjordal JM, Couppe C, Chow RT, et al. A systematic rev iew of low level laser therapy w ith location-speci?c doses for p ain from ch ronic joint disorders. Aust J Physiother. ):107-16.16. Oberoi S, Zampe rlini-Netto G, Beyen e J, et al. Effect of prophylactic low level laser the rapy on oral mucos itis: a systematic review a nd meta-analysis. P LoS One. 2014;9 (9): e107418 .17. Migliorati C, Hewson I, Lalla RV, et al. Systematic review of laser and other light therapy for the manag ement of oral mucosi tis in canc er patients. Suppor t Care Cancer. 2013;21(1):333-41.18. Peterson DE, Bensa doun RJ, Roil a F, et al. Management of oral and gast roin-testinal mucositis: ESMO Clinical Practice Guidelines. Ann Oncol. 2011;22 Suppl 6:vi78 -84.19. Bensinger W, Schubert M, An g KK, et al. NCCN Task Force Repor t. preven-tion and manageme nt of mucositis in can cer care. J Nat l Compr Ca nc Netw. 2008;6 Suppl 1:S1-21; quiz S2-4.20. Hymes SR, S trom EA, Fife C. Radiat ion dermatitis: cli nical presentati on, patho-physiolo gy, and treatment 2006. J Am Acad Derm atol. ):28-46.21. Wong RK , Bensadoun RJ, Boer s-Doets CB, et al. Clinical practice guidelines for the prevention and treatment of acute and late radiation re actions from the MASCC Ski n Toxicity Stu dy Group. Support Care Cance r. 2013;21(10):2933-48.KEY MESSAGES FOR CLINICAL PRACTICE1.
Cancer therapy can have serious side effects such as, oral mucositis, lymphoedema, radiodermatitis, osteonecrosis of the jaw, chemotherapy-induced peripheral neuropathy, and xerostomia/hyposalivation.2.
PBMT is a non-invasive therapy based on the application of visible or near-infrared light on tissue to sti-mulate the wound healing process and reduce in?ammation and pain. 3.
There is a growing body of evidence that PBMT is bene?cial for the prevention and/or management of acute and chronic cancer therapy-related side effects.4.
Future studies are necessary to elucidate appropriate treatment and irradiation parameters and to exclu-de possible effects of PBMT on the tumour process.REVIEW ONCOLOGY
VOLUME11DECEMBER2017374Ziekenhuis prijs
80 mg x 30 tab
40 mg x 30 tab
6.100EURIn patients with EGFR T790M mutation–positive NSCLCBREAK THROUGH THET790MRESISTANCE BARRIER NEW &REIMBURSEDESSENTIELE GEGEVENS Dit geneesmiddel is onderworpen aan aanvullende monitoring. Daardoor kan snel nieuwe veiligheidsinformatie worden vastgesteld. Beroepsbeoefenaren in de gezondheidszorg worden verzocht alle vermoedelijke bijwerkingen te melden. Zie rubriek ‘Bijwerkingen’ voor het rapporteren van bijwerkingen. 1. NAAM VAN HET GENEESMIDDEL TAGRISSO 40?mg fi lmomhulde tabletten TAGRISSO 80?mg fi lmomhul-de tabletten 2. KWALITATIEVE EN KWANTITATIEVE SAMENSTELLING TAGRISSO 40 mg tabletten Elke tablet van 40?mg bevat 40?mg osimertinib (als mesilaat). TAGRISSO 80 mg tabletten Elke tablet van 80?mg bevat 80?mg osimertinib (als mesilaat). Voor de volledige lijst van hulpstoffen, zie rubriek ‘Lijst van hulpstoffen’ van de SKP. 3. FARMACEUTISCHE VORM Filmomhulde tablet (tablet). TAGRISSO 40?mg tabletten Beige, ronde, bicon-vexe tablet van 9?mm, met één blanco zijde en de inscriptie “AZ” en “40” op de andere zijde. TAGRISSO 80?mg tabletten Beige, ovale, biconvexe tablet van 7,25 x 14,5?mm, met één blanco zijde en de inscriptie “AZ” en “80” op de andere zijde. 4. KLINISCHE GEGEVENS 4.1 Therapeutische indicaties TAGRISSO is ge?ndiceerd voor de behandeling van volwassen pati?nten met lokaal gevorderde of gemetastaseerde niet-kleincellige longkanker (NSCLC) met een epidermale groeifactor receptor (EGFR) T790M-mutatie. 4.2 Dosering en wijze van toediening De behandeling met TAGRISSO dient te worden gestart door een arts die ervaren is in het toepassen van therapie?n tegen kanker. Wordt het gebruik van TAGRISSO overwogen voor de behandeling van lokaal gevorderde of gemetastaseerde NSCLC, dan is het noodzakelijk dat de status van de EGFR T790M-mutatie is vastgesteld. De status van de EGFR T790M-mutatie dient te worden bepaald met behulp van een gevalideerde testmethode (zie rubriek?‘Bijzondere waarschuwingen en voorzorgen bij gebruik’ van de SKP). Dosering De aanbevolen dosis is eenmaal daags 80?mg osimertinib tot progressie van de ziekte of een onaanvaardbare toxiciteit. Als er een dosis TAGRISSO wordt vergeten, dan dient de dosis alsnog te worden in-genomen, tenzij de volgende dosis al binnen 12 uur moet worden genomen. TAGRISSO kan elke dag rond hetzelfde tijdstip met of zonder voedsel worden ingenomen. Dosisaanpassingen Afhankelijk van de veiligheid en verdraagbaarheid van de individuele pati?nt kan er een dosisonderbreking en/of dosisreductie nodig zijn. Als een dosisreductie noodzakelijk is, dan dient de dosis te worden verlaagd naar eenmaal daags 40?mg. In tabel 1 worden richtlijnen gegeven voor dosisreductie bij bijwerkingen door toxiciteit. Tabel 1 van de aangepaste SPK. Aanbevolen dosisaanpassingen voor TAGRISSO in deze volgorde DoelorgaanoBijwerkingaoDosisaanpassing Longen oILD/pneumonitisoBe?indig het gebruik van TAGRISSO perma-nent HartoQTc-interval groter dan 500? ms op minstens twee verschillende ECG’soOnderbreek het gebruik van TAGRISSO tot het QTc-interval kleiner is dan 481?ms of is hersteld naar de uitgangswaarde als de uitgangswaarde van QTc groter is dan of gelijk is aan 481?ms. Herstart met een gereduceerde dosis (40?mg) oVerlenging van het QTc-interval met verschijnselen/symptomen van een ernstige ritmestoornisoBe?indig het gebruik van TAGRISSO permanent Overige oBijwerking van graad 3 of hogeroOnderbreek het gebruik van TAGRISSO gedurende maximaal 3?weken oAls de bijwerking van graad 3 of hoger is verbeterd naar graad 0-2 nadat het gebruik van TAGRISSO gedurende maximaal 3?weken werd onderbro-kenoHet gebruik van TAGRISSO kan opnieuw worden gestart met dezelfde dosis (80?mg) of een lagere dosis (40?mg) oDe bijwerking van graad 3 of hoger is niet verbeterd naar graad 0-2 nadat het gebruik van TAGRISSO gedurende maximaal 3?weken werd onderbrokenoBe?indig het gebruik van TAGRISSO permanent a Opmerking: Classifi catie van de ernst van de bijwerkingen op basis van de National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), versie 4.0. ECG’s: E QTc: QT-interval gecorrigeerd voor frequentie van de hartslag
Bijzondere pati?ntengroepen Er is geen dosisaanpassing nodig op basis van de leeftijd, het lichaamsgewicht, het geslacht, de etniciteit of het rookgedrag van de pati?nt (zie rubriek ‘Farmacokinetische eigenschappen’ van de SKP). Leverinsuffi ci?ntie Er zijn geen klinische onderzoeken uitgevoerd om specifi ek het effect van leverinsuffi ci?ntie op de farmacokinetiek van osimertinib te onderzoeken. Er wordt geen dosisaanpassing aanbevolen voor pati?nten met een lichte leverinsuffi ci?ntie (totale bilirubinewaarde ≤?bovenlimiet van normaal (ULN) en aspartaataminotransfera-se (ASAT) &?ULN of totale bilirubinewaarde &?1,0 tot 1,5x ULN en willekeurige ASAT) of met een matige leverinsuffi ci?ntie (totale bilirubinewaarde 1,5 tot 3x?ULN en willekeurige ASAT). Voorzichtigheid is echter geboden bij het toedienen van TAGRISSO aan dergelijke pati?nten. De veiligheid en werkzaamheid van dit geneesmiddel bij pati?nten met ernstige leverinsuffi ci?ntie zijn niet vastgesteld. Totdat er aanvullende gegevens bekend worden, wordt het gebruik bij pati?nten met ernstige leverinsuffi ci?ntie afgeraden (zie rubriek ‘Farmacokinetische eigenschappen’ van de SKP). Nierinsuffi ci?ntie Er zijn geen klinische onderzoeken uitgevoerd om specifi ek het effect van nierinsuffi ci?ntie op de farmacokinetiek van osimertinib te onderzoeken. Er wordt geen dosisaanpassing aanbevolen voor pati?nten met lichte, matige of ernstige nierinsuffi ci?ntie. Er zijn beperkte gege-vens beschikbaar van pati?nten met ernstige nierinsuffi ci?ntie. De veiligheid en werkzaamheid van dit geneesmiddel bij pati?nten met terminaal nierfalen (creatinineklaring [CLcr] &?15? ml/min, zoals berekend met de Cockroft-Gault-formule) of bij pati?nten die dialyse ondergaan, zijn niet vastgesteld. Voorzichtigheid is geboden bij de behandeling van pati?nten met ernstige en terminale nierinsuffi ci?ntie (zie rubriek ‘Farmacokineti-sche eigenschappen’ van de SKP). Pediatrische pati?nten De veiligheid en werkzaamheid van TAGRISSO bij kinderen of jongeren tot 18?jaar zijn niet vastgesteld. Er zijn geen gegevens beschikbaar. Wijze van toediening Dit geneesmiddel is bedoeld voor oraal gebruik. De tablet dient in zijn geheel met water te worden doorgeslikt en mag niet worden gedeeld, gekauwd of fi jngemalen. Als de pati?nt niet in staat is om de tablet door te slikken, dan kan de tablet worden opgelost in 50?ml niet-koolzuurhoudend water. De tablet moet zonder deze eerst te verpulveren aan het water worden toegevoegd. Er moet worden geroerd tot de tablet is opgelost en onmiddellijk daarna moet de oplossing worden opgedronken. Het glas moet daarna weer tot de helft worden gevuld, om ervoor te zorgen dat er geen residu achterblijft. Dit water moet onmiddellijk worden opgedronken. Er mogen geen andere vloeistoffen worden toegevoegd. Als het geneesmiddel via een maagsonde moet worden toegediend, dan moet hetzelfde proces als hierboven worden gevolgd, maar met gebruik van een volume van 15?ml voor de aanvankelijke oplossing en 15?ml voor het doorspoe-len van het residu. De resulterende 30?ml vloeistof moet met geschikte waterspoelingen worden toegediend volgens de instructies van de fabrikant van de maagsonde. De oplossing en het residu moeten uiterlijk 30?minuten nadat de tabletten aan het water zijn toegevoegd, worden toegediend. 4.3 Contra-indicaties Overgevoeligheid voor de werkzame stof of voor een van de in rubriek ‘Lijst van hulpstoffen’ van de SKP vermelde hulpstof-fen. Sint-janskruid mag niet gelijktijdig worden gebruikt met TAGRISSO (zie rubriek ‘Interacties met andere geneesmiddelen en andere vormen van interactie’ van de SKP) 4.4 Bijwerkingen Samenvatting van het veiligheidsprofi el Onderzoeken bij EGFR T790M-mutatiepositieve NSCLC-pati?nten eerder behandeld met een EGFR TKI De onderstaande gegevens geven de blootstelling aan TAGRISSO weer bij 690? pati?nten met EGFR T790M-mutatiepositieve niet-kleincellige longkanker (NSCLC) die eerder EGFR TKI-therapie kregen. Deze pati?nten kregen TAGRISSO in een do-sering van 80?mg per dag in één gerandomiseerd fase III-onderzoek (AURA3 – uitsluitend tweedelijns) en twee eenarmige onderzoeken (AURAex en AURA 2 – tweedelijns of later) (zie rubriek ‘Farmacodynamische eigenschappen’ van de SKP). In AURA3 was de mediane duur van de onder-zoeksbehandeling 8,1?maanden voor pati?nten in de TAGRISSO-arm (n?=?279) en 4,2?maanden voor pati?nten in de chemotherapie-arm (n?=?136). Het merendeel van de pati?nten in de samengevoegde fase II-onderzoeken had voorafgaand meerdere behandelingen ondergaan: 68% had ten minste twee voorafgaande behandelregimes gekregen en 46% had drie of meer voorafgaande therapielijnen gekregen. Naast een EGFR TKI-the-rapie, kreeg ongeveer twee derde (63%) van de pati?nten voorafgaand platinumhoudende chemotherapie. De algehele mediane duur van de on-derzoeksbehandeling in AURAex en AURA 2 was 13?maanden (n?=?411). De meeste causaal gerelateerde bijwerkingen hadden een ernst van graad 1 of 2. De meest frequent gemelde bijwerkingen met een causaal verband met het geneesmiddel waren diarree (44%) en huiduitslag (41%). In beide onderzoeken kwamen bijwerkingen (ongeacht causaliteit) van graad 3 (26%) en graad 4 (2%) voor. Bij pati?nten die werden behandeld met eenmaal daags 80?mg TAGRISSO, werd bij 2,3% van de pati?nten de dosis gereduceerd als gevolg van bijwerkingen. Bij 6,5% werd de behande-ling be?indigd vanwege causaal gerelateerde bijwerkingen of afwijkende laboratoriumparameters. Pati?nten met een voorgeschiedenis van ILD, door medicatie ge?nduceerde ILD, bestralingspneumonitis waarvoor een behandeling met stero?den noodzakelijk was of elk bewijs van klinisch actieve ILD waren uitgesloten van deelname aan klinische onderzoeken. Pati?nten met klinisch relevante afwijkingen in ritme of geleiding op een elektrocardiogram (ECG) in rust (bijv. met een QTc-interval groter dan 470?ms), waren uitgesloten van deelname aan deze klinische onderzoeken. Pati?nten werden beoordeeld op LVEF tijdens de screening en daarna elke 12?weken. Tabel met causaal gerelateerde bijwerkingen Bijwerkingen zijn ingedeeld in de frequentiecategorie?n in tabel?2 waar mogelijk gebaseerd op de incidentie van vergelijkbare bijwerkingenrapportages in een samengevoegde gegevensreeks van de 690?eerder behandelde EGFR T790M-mutatiepositieve pati?nten die TAGRISSO kregen met een dosering van 80?mg per dag in de AURA3-, AURAex- en AURA 2-onderzoeken. De causaal gerelateerde bijwerkingen worden vermeld volgens systeem/orgaanklasse van MedDRA. Binnen een systeem/orgaanklasse worden de bijwerkingen van het geneesmiddel gerangschikt naargelang hun fre-quentie, waarbij de meest frequent voorkomende bijwerkingen als eerste worden vermeld. Binnen elke frequentiegroep worden de bijwerkingen van het geneesmiddel weergegeven in volgorde van afnemende ernst. De bijbehorende frequentiecategorie voor elke bijwerking wordt gebaseerd op de CIOMS III-conventie en wordt als volgt gedefi nieerd: zeer vaak (≥?1/10); vaak (≥?1/100 tot &?1/10); soms (≥?1/1000 tot &? 1/100); zelden (≥?1/10.000 tot &?1/1000); zeer zelden (&?1/10.000) en niet bekend (kan met de beschikbare gegevens niet worden bepaald). Tabel?2 geeft een overzicht van de bijwerkingen uit AURAex- (fase?II), AURA 2- en AURA3-onderzoeken die voorkwamen bij pati?nten die minstens één dosis TAGRIS-SO ontvingen. Tabel 2 van de aangepaste SKP. Gemelde causaal gerelateerde bijwerkingen in AURAa-onderzoeken in deze volgorde: MedDRA-sys-teem/orgaanklasseoMedDRA-termoCIOMS-descriptor/algemene frequentie (alle CTCAE-graden)boFrequentie voor CTCAE-graad 3 of hoger Ademhalingsstelsel-, borstkas- en mediastinum aandoeningenoInterstiti?le longaandoeningcoVaak (3,2%)d o1,3% Maagdarmstelsel-aandoe-ningenoDiarreeoZeer vaak (44%)o1,0% oStomatitisoZeer vaak (15%) o0% OogaandoeningenoKeratitiseoSoms (0,9%)o0% Huid- en onder-huid-aandoeningenoRashfoZeer vaak (41%) o0,7% oDroge huidgoZeer vaak (29%) o0% oParonychiahoZeer vaak (27%)o0% oPruritusi oZeer vaak (15%)o0% OnderzoekenoVerlenging van het QTc-intervaljoSoms (0,7%)o (Bevindingen op basis van testresultaten weergegeven als veranderingen in CTCAE-graden)oAantal bloedplaatjes verlaagdkoZeer vaak (54%)o2,1% oLeukocyten verlaagdkoZeer vaak (66%)o2,4% oNeu-trofi elen verlaagdkoZeer vaak (32%)o4,3% - a De gegevens zijn de cumulatieve gegevens van fase III- (AURA3) en fase II- (AURAex en AURA 2)
in het overzicht zijn alleen de bijwerkingen opgenomen die voorkwamen bij pati?nten die minstens één dosis TAGRISSO ontvingen. b National Cancer Institute Criteria for Adverse Events, versie 4.0. c Met inbegrip van gevallen die werden gemeld binnen de algemene termen: interstiti?le longaandoening en pneumonitis. d Er werden 4 bijwerkingen van CTCAE-graad 5 (dodelijk) gemeld. e Met inbegrip van gevallen die werden gemeld binnen de algemene termen: keratitis, keratitis punctata, cornea-erosie, cornea-epitheeldefecten en corneadefecten. f Met inbe-grip van gevallen die werden gemeld binnen de algemene termen voor bijwerkingen met rash: rash, gegeneraliseerde rash, erythemateuze rash, vlekkerige rash, maculopapuleuze rash, papuleuze rash, pustuleuze rash, erytheem, folliculitis, acne, dermatitis en acne?forme dermatitis. g Met inbegrip van gevallen die werden gemeld binnen de algemene termen: droge huid, huidkloven, xerose, eczeem. h Met inbegrip van gevallen die werden gemeld binnen de algemene termen: nagelbedstoornis, nagelbedontsteking, nagelbedbroosheid, verkleuring nagel, nagelafwijking, nagel-toxiciteit, nageldystrofi e, nagelinfectie, geribbelde nagel, onychoclasis, onycholyse, onychomadesis, paronychia. i Met inbegrip van gevallen die werden gemeld binnen de algemene termen: pruritus, gegeneraliseerde pruritus, ooglidpruritus. j Vertegenwoordigt de incidentie van pati?nten met een verlenging van het QTcF &?500 msec. k Vertegenwoordigt de incidentie van laboratoriumbevindingen, niet van gemelde bijwerkingen.Tabel 3. Bijwerkingen in het AURA3aMedDRA-systeem/orgaanklasse TAGRISSO totale frequentie (N = 279)Chemotherapie (Pemetrexed/Cisplatine of Pemetrexed/Carboplatine) totale frequentie (N = 136)NCI-graden Elke graad (%) Graad 3 of hoger (%) Elke graad (%) Graad 3 of hoger ( %)MedDRA-voorkeurstermAdemhalingsstelsel-, borstkas- en mediastinum aandoeningenInterstiti?le longaandoeningb,c 3,6 0,4 0,7 0,7OogaandoeningenKeratitisd
1,1 0 0,7 0Maagdarmstelsel-aandoeningenDiarree 41 1,1 11 1,5Stomatitis 15 0 15 1,5Huid- en onderhuid-aandoeningenRashe34 0,7 5,9 0Droge huidf23 0 4,4 0Paronychiag22 0 1,5 0Pruritush13 0 5,1 0Verlenging van het QTc-intervali1,4 0 0,7 0(Bevindingen op basis van testresultaten weergegeven als veranderingen in CTCAE-graden)Aantal bloedplaatjes verlaagdj46 0,7 48 7,4Leukocyten verlaagdj61 1,1 75 5,3Neutrofielen verlaagdj27 2,2 49 12a De gegevens zijn de cumulatieve gegevens van het AURA3- in het overzicht zijn alleen de bijwerkingen opgenomen die voorkwamen bij pati?nten die minstens één dosis TAGRISSO ontvingen. b Met inbegrip van gevallen die werden gemeld binnen de algemene termen: interstiti?le longaandoening en pneumonitis. c Er werd 1 bijwerking van CTCAE-graad 5 (dodelijk) gemeld. d Met inbegrip van gevallen die werden gemeld binnen de algemene termen: keratitis, keratitis punctata, cornea-erosie, cornea-epitheeldefecten en corneadefecten. e Met inbegrip van gevallen die werden gemeld binnen de algemene termen voor bijwerkingen met rash: rash, gegeneraliseerde rash, erythemateuze rash, vlekkerige rash, maculopapuleu-ze rash, papuleuze rash, pustuleuze rash, erytheem, folliculitis, acne, dermatitis en acne?forme dermatitis. f Met inbegrip van gevallen die werden gemeld binnen de algemene termen: droge huid, huidkloven, xerose, eczeem. g Met inbegrip van gevallen die werden gemeld binnen de algemene termen: nagelstoornis, nagelbedstoornis, nagelbedontsteking, nagelbedbroosheid, verkleuring nagel, nagelafwijking, nageldystrofi e, nagelinfectie, geribbelde nagel, onychoclasis, onycholyse, onychomadesis, paronychia. h Met inbegrip van gevallen die werden gemeld binnen de algemene ter-men: pruritus, gegeneraliseerde pruritus, ooglidpruritus. i Vertegenwoordigt de incidentie van pati?nten met een verlenging van het QTcF &?500msec. j Vertegenwoordigt de incidentie van laboratoriumbevindingen, niet van gemelde bijwerkingen. Veiligheidsbevindingen uit de eenarmige AURAex- en AURA 2-fase II-onderzoeken kwamen in het algemeen overeen met de bevindingen uit de AURA3 TAGRISSO-arm. Geen aanvullende of onverwachte toxiciteit is waargenomen en bijwerkingen zijn ingedeeld op type, ernst en frequentie. Beschrijving van geselecteerde bijwerkingen Interstiti?le lon-gaandoening (ILD) In de AURA-onderzoeken bedroeg de incidentie van ILD 8,2% bij pati?nten van Japanse etniciteit, 1,9% bij pati?nten van niet-Ja-panse Aziatische etniciteit en 2,9% bij niet-Aziatische pati?nten. De mediane tijd tot de aanvang van ILD of ILD-achtige bijwerkingen, welke causaal waren gerelateerd, bedroeg 2,8 maanden (zie rubriek ‘Bijzondere waarschuwingen en voorzorgen bij gebruik’ van de SKP). Verlenging van het QTc-interval Van de 833?pati?nten in de AURA-onderzoeken behandeld met 80? mg TAGRISSO, werd bij 0,7% van de pati?nten (n?=?6) een QTc waargenomen van meer dan 500? 2,9% van de pati?nten (n?=?24) vertoonde een verhoging ten opzichte van de uitgangswaarde van QTc van meer dan 60?ms. Een farmacokinetische analyse met TAGRISSO voorspelde een concentratie-afhankelijke toename in de verlenging van het QTc-in-terval. Er zijn geen QTc-gerelateerde aritmie?n gemeld in de AURA-onderzoeken (zie rubrieken ‘Bijzondere waarschuwingen en voorzorgen bij ge-bruik’ en ‘Farmacodynamische eigenschappen’ van de SKP). Gastro-intestinale effecten In de AURA-onderzoeken is diarree gerapporteerd bij 43,5% van de pati?nten, waarvan 36,8% een bijwerking van graad 1 was, 5,5% van graad 2 en 1,0% van graad 3; bijwerkingen van graad 4 of 5 zijn niet gerapporteerd. Een vermindering van de dosis was noodzakelijk bij 0,3% van de pati?nten en een onderbreking van de toediening bij 0,7%. Eén voorval (0,1%) leidde tot stopzetten. In AURA3 was de mediane tijd tot de aanvang 22?dagen en was de mediane duur van de bijwerkingen van graad?2 5,5?dagen. Oudere pati?nten In AURA3 (N?=?279) was 41% van de pati?nten 65?jaar of ouder en 15% daarvan was 75?jaar of ouder. Verge-leken met jongere pati?nten (&?65) hadden meer pati?nten van ≥?65 jaar gemelde bijwerkingen die leidden tot een aanpassing van de dosis van het onderzochte geneesmiddel (onderbreking of reductie) (5,3% versus 4,2%). Het type gemelde bijwerkingen was vergelijkbaar, ongeacht de leeftijd. Oudere pati?nten meldden meer bijwerkingen van graad 3 of hoger in vergelijking met jongere pati?nten (5,3% versus 2,4%). Er werden geen ver-schillen in werkzaamheid waargenomen tussen oudere pati?nten en jongere pati?nten. De waargenomen resultaten voor veiligheid en werkzaam-heid komen overeen met die van de AURA fase II-onderzoeken. Melding van vermoedelijke bijwerkingen Het is belangrijk om na toelating van het geneesmiddel vermoedelijke bijwerkingen te melden. Op deze wijze kan de verhouding tussen voordelen en risico’s van het geneesmiddel voortdu-rend worden gevolgd. Beroepsbeoefenaren in de gezondheidszorg wordt verzocht alle vermoedelijke bijwerkingen te melden via: Belgi? Federaal agentschap voor geneesmiddelen en gezondheidsproducten, Afdeling Vigilantie EUROSTATION II Victor Hortaplein, 40/ 40 B-1060 Brussel Website: www.fagg.be e-mail: adversedrugreactions@fagg-afmps.be 5. HOUDER VAN DE VERGUNNING VOOR HET IN DE HANDEL BRENGEN AstraZeneca AB SE-151 85 S?dert?lje Zweden 6. NUMMER(S) VAN DE VERGUNNING VOOR HET IN DE HANDEL BRENGEN EU/1/16/ EU/1/16/ EU/1/16/ EU/1/16/ 7. AFLEVERINGSWIJZE Geneesmiddel op medisch voorschrift 8. DATUM VAN HERZIENING VAN DE TEKST 07-2017 Gedetailleerde informatie over dit geneesmiddel is beschikbaar op de website van het Europees Geneesmiddelenbureau http://www.ema.europa.eu.NS ID XL-0010-RD05/2017-LBAZ-Tagrisso pub A4 NL (SH 9128) update 07/2017.indd
1 29/08/17
09:4422. Schindl M, Kerschan K, Sc hindl A, et al. Inductio n of complete wound heal-ing in recalcitrant ulcers by low-intensity laser irradiation depends on ulcer cause and size. Photodermatol Photoimmunol Photomed. 1999;15(1):18-21.23. DeLand M M, Weiss RA, McDanie l DH, et al. Treatment of radiation-in duced dermatitis with light-emit ting diode (LED) photomodulatio n. Lasers Surg Med. 2007;39(2):164-8.24. Fife D, Rayhan DJ, Behnam S, et al. A rando mized, controlled, double-blind study of lig ht emitting diode photomodu lation for the prevention of radiation der-matitis in p atients wi th breast cancer. Dermatol Surg. 2):1921-7.25. Censabella S, Claes S, Robi jns J, et al. Photobiomodulation for the m anage-ment of radiation dermatitis: the D ERMIS tr ial, a pilot study of MLS laser therapy in breast ca ncer patients. Support Care Cancer. 2016;24(9):3925-33.26. Seretny M, Cur rie GL, Sena ES, et al. Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: A systematic review and me-ta -a n al y si s.
2014;15 5( 12):2461-7 0.27. Kandula T, Farrar MA, Kie rnan MC, et al. Neurophysiological and clin ical out-comes in chemotherapy-induced neuropathy in cancer. Clin Neurophysiol. 20 17;12 8( 7 ): 1166-75 .28. Yamada K, Kaise H, Og ata A. Low-level laser therapy for sym ptoms induced by breast ca ncer treatments. 2010 ASCO Breast Cancer Sy mposiu m. 2010.29. Hsieh YL, Chou LW, Hong SF, et al. Laser acupuncture attenuates oxali pla-tin-induced peripheral neuropathy i n patients w ith gastro intestina l cancer: a p i-lot prospective coho rt stu dy. Acupunct Me d. 2016;34(5):398-405.30. Argenta PA, Ballman K V, Geller MA, et al. T he effect of photobiom odulation on chemotherapy-induced peripheral neuropathy: A randomized, sham-con-trolled clinical trial. Gynecol Oncol. 2017;144(1):159-66.31. Paulo S, Abrantes AM, La ranjo M, et al. Bisphosph onate-related osteone-crosis of the jaw: speci? cities. On col Rev. 2014;8(2):254.32. Ruggiero SL, Dodson TB, Fantasia J, et al. Ame rican Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw--2014 update. J Oral Max illofac Surg. 2014;72(10):1938-56.33. Gomes F V, Mayer L, Massotti FP, et al. Low-level laser thera py improves peri-implant bone formation: resonance frequency, electron microscopy, and stereolog y ?nding s in a rabbit m odel. Int J Oral Maxillofac Surg. ):245-51.34. Carroll JD, Milward MR, Co oper PR, et al. Developme nts in low level light therapy (L LLT) for dentistry. Dent Mate r. 2014;30(5):465-75.35. Latif yan S, Genot MT, Klastersky J. Bi sphosphonate-related osteone crosis of the jaw: a review of the potenti al ef?cacy of low-level laser therapy. Support Care Cancer. 2016;24(9):3687-93.36. Jensen SB, Pedersen A M, Vissin k A, et al. A systematic review of s alivar y gland hypofunction and xerostomia induced by cancer therapies: prevalence, severit y and impact on quality of life. Support Care Cance r. 2010;18(8):1039-60.37. Cowen D, Tardieu C, Schubert M, et al. Low e nergy He lium-Neon laser in the prevent ion of oral mucositis in patients u ndergoing bone ma rrow transplant: results of a do uble blin d randomized trial. Int J Radiat On col Biol Phys. ):6 97-703.38. Simoes A , de Campos L, d e Souza DN, et a l. Laser phototherapy as topi-cal prophylaxi s against radiation-i nduced xe rostomia. Ph otomed Las er Surg. 20 10 ; 28 ( 3 ): 3 57- 6 3 .39. Arbabi-Kalati F, Arbabi-K alati F, Moridi T. Evaluation of the effec t of low level laser on prevention of ch emother apy-induced mucositis. Acta Med Iran. 2013 ;51(3 ):157- 62.40. Oton-Leite A F, Elias LS, Morais MO, et al. Effect of low level laser therapy in the reduction of oral c omplications in pat ients with cancer of the head and neck submit ted to radioth erapy. Spec Care D entist. ):294-300.41. Saleh J, Fig ueiredo M A, Cher ubini K, et al. Ef fect of low-level laser therapy on radiotherapy-induced hyposalivation and xerostomia: a pilot study. Photomed Laser Su rg. ):546- 52.ALL PUBLISHED BJMO ARTICLES ARE AVAILABLE ON OUR WEBSITE:WWW.ARIEZ.COMAs well as all published articles from our other medical journals.
ArticleFull-text availableJan 2013ArticleApr 2017ArticleDec 2016Show moreProject[...]ArticleAugust 2016 · Breast cancer is the most common cancer in women worldwide, with an incidence of 1.7 million in 2012. Breast cancer and its treatments can bring along serious side effects such as fatigue, skin toxicity, lymphedema, pain, nausea, etc. These can substantially affect the patients’ quality of life. Therefore, supportive care for breast cancer patients is an essential mainstay in the treatment.... [Show full abstract]ArticleFebruary 2018 · Objective:
Acute radiodermatitis (RD) is a distressing and painful skin reaction that occurs in 95% of the patients undergoing radiotherapy (RT). The aim of this study was to evaluate the effectiveness of photobiomodulation therapy (PBMT) in the prevention of acute RD in breast cancer (BC) patients undergoing RT.
This study was a randomized, placebo-controlled trial including 120... [Show full abstract]ArticleSeptember 2016 ·
HPLT; LLLT ArticleApril 2016 · Purpose
The aim of this study was to assess the effectiveness and acceptability of photobiomodulation using MLS(R) laser therapy (LT) in the management of acute radiation dermatitis (RD).
We compared two successive groups of breast cancer patients undergoing identical radiotherapy regimens post-lumpectomy. Both groups received our standard skin care but the second group received six... [Show full abstract]Conference PaperMarch 2015Introduction
Radiodermatitis (RD) is a common and distressing side effect of radiotherapy.
Investigate the efficacy of low-level laser therapy (LLLT) as a treatment for RD in breast cancer patients.
For this prospective study two successive groups of breast cancer patients undergoing identical radiotherapy regime post-lumpectomy were compared. The control group (CTRL group,... [Show full abstract]Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.This publication is from a journal that may support self archiving.Last Updated: 27 Feb 18