Background and purpose
Methods and materials
Results
Antibodies
Cetuximab
Substance | Author(s) | Year | Study type | N | Tumour | RT dose/ChTx/technique | Toxicity |
---|---|---|---|---|---|---|---|
Cetuximab | Bonner et al. [10] | 2006 | Phase III | 211 (cetux-arm) | LA-HNSCC | 70-78.8 Gy (hyper-fractionated) | Significant differences or trend in arms: 8% grade III-V acneiform rash, 1% grade III-V voice alteration, 1% grade III-V infusion reaction |
Koutcher et al. [24] | 2009 | Retrospective | 115 | LA-HNSCC | 66 Gy/69.96 Gy | 3% grade IV radio-dermatitis, 19% grade III radio-dermatitis | |
Studer et al. [25] | 2011 | Prospective | 99 | HNSCC | 66-70 Gy, 30/99 switch from Cis | 34% grade II/IV dermatitis | |
Hallqvist et al. [28] | 2010 | Phase II | 75 | NSCLC | 68 Gy, Ind. ChTx Doc/Cis + concomitant Cetux | 1% grade V pneumonitis, 4% grade III pneumonitis, 5% grade III + IV hypersensitivity, 15% grade III + IV febrile neutropenia, 4% III skin reactions | |
Jensen et al. [122] | 2010 | Retrospective | 73 | HNSCC | 22 pts Re-RT (50-60 Gy), 66-70 Gy | 5% grade III allergic reaction, 4% grade III acneiform rash | |
Garcia-Huttenlocher et al. [123] | 2009 | Retrospective | 65 | HNSCC | Median 66 Gy (IMRT) | Grade III: skin toxicity 28%, mucositis 25% | |
Rödel et al. [115] | 2008 | Phase I/II | 12/48 | Rectal cancer | 50,4 Gy +Capecitabine + Oxaliplatin | Phase II only Grade IV/V: Leukopenia, thrombocytopenia, Diarrhea, Creatinine elevation, e-lyte derivation, infection each 2% | |
Safran et al. [31] | 2008 | Phase II | 60 | Esophago-gastric-cancer | Cetux/Carbo/Tax + 50.4 Gy | 23% grade III rash, 15% grade III/IV esophagitis, 5% III + IV hypersensitivity, 3% grade IV neutropenia (10% grade III), 2% IV anemia (8% grade III) | |
Jatoi et al. [124] | 2010 | Phase II | 57 | NSCLC | 60 Gy | 2% grade IV each: dysphagia/hypomagnesemia/dyspnea/headache/thrombosis/GI hemorrhage, 7% grade III rash | |
Horisberger et al. [30] | 2009 | Phase II | 50 | Rectal cancer | 50,4 Gy + Capecitabine + Irinotecan | Leukopenia 4% grade III and IV each Grade III: Diarrhea 60%, abdominal pain 8%, ALAT/ASAT elevation 20%, Acneiform skin rash 12%, anemia, nausea/vomiting, bilirubin elevation, proctitis each 4% | |
Koutcher et al. [125] | 2011 | Retrospective | 49 | LA-HNSCC | 69.96 Gy (IMRT) (comparison vs. concomitant Cis) | 20% late grade III + IV toxicity | |
Walsh et al. [26] | 2011 | Retrospective | 48 (14 excluded because of SIB) | HNSCC | Cis vs. Cetux (66-70 Gy) | 44% ≥ grade III skin toxicity, 52% ≥ grade III mucositis, 6% ≥ grade III acneiform rash | |
Buiret et al. [126] | 2010 | Retrospective multicenter | 46 | HNSCC | Ind. ChTx Doc/Cis/5-FU, RIT (70 Gy) | No grade IV toxicity | |
Garcia-Huttenlocher et al. [127] | 2008 | Retrospective | 46 | HNSCC | Median 66 Gy (IMRT) | 20% grade III skin toxicity, 4% grade III mucositis | |
Merlano et al. [128] | 2010 | Phase II | 45 | HNSCC | Up to 70 Gy, three cycles Cis/5-FU, split course RT, RT + cetux | 2% grade IV leukopenia (38% grade III), 7% grade IV neutropenia (33% grade III), 2% grade IV thrombopenia (13% grade III), 36% grade IV stomatitis (29% grade III), 73% grade III radiodermatitis, 7% grade III rash | |
Koukourakis et al. [60] | 2010 | Phase I | 43 | LA-HNSCC | 21 × 2.7 Gy (56.7 Gy) + amifostine + Cis | 16% grade III + IV mucositis, 2% grade III + IV skin toxicity | |
Suntharalingam et al. [129] | 2011 | Phase II | 43 | LA-HNSCC | 70,2 Gy (3D/IMRT) + Paclitaxel, Carboplatin, | Grade 3 mucositis (79%), rash (9%), leukopenia (19%), neutropenia (19%), and RT dermatitis (16%) | |
De Vita et al. [130] | 2011 | Phase II | 41 | Esophageal cancer | Ind. FOLFOX4 + 50.4 Gy/Cetux | 30% grade II/IV skin toxicity/neutropenia | |
Bertolini et al. [117] | 2009 | Phase II | 40 | LA rectal cancer | 50-50.4 Gy + neoadj. Cetux/Cetux + 5-FU concomitant | 8% grade III/IV skin rash, 8% grade III/IV hypersensitivity, 13% grade III/IV GI toxicity, 3% grade III/IV febrile neutropenia | |
Kim et al. [98] | 2011 | Phase II | 40 | Rectal cancer | Capecitabine + Cetux + Irinotecan + 50.4 Gy | 3% grade IV leukopenia, 3% grade III rash | |
Machiels et al. [119] | 2007 | Phase I/II | 40 | Rectal cancer | 45 Gy + Capecitabine | 3% grade III/IV allergic reaction, 3% grade III/IV dermatitis | |
Argiris et al. [131] | 2010 | Prospective | 39 | LA-HNC | Induction Docetaxel/Cis/Cetux + concurrent Cisplatin/Cetux/70-74 Gy-RT | Grade III/IV: oral mucositis 46%, Anemia 21%, in-field dermatitis 23%, Dysphagia 41%, Thrombocytopenia 10%, Neutropenia 31%, febrile neutropenia 5%, infection 18%, fatigue 13%, nausea 10%, vomiting 3%, renal failure 3%, DVT 5%, bleeding 5%. | |
Velenik et al. [118] | 2010 | Phase II | 37 | Rectal cancer | 45 Gy RT + capecitabine (neoadjuvant) | Grade III: diarrhea 11%, anorexia 3%, hepatotoxicity 3%, in-field-dermatitis 16%, infection 3%, hypersensitivity 5%. | |
Heron et al. [132] | 2011 | Matched pair retrospective | 35 | HNSCC | SBRT Re-RT | No significant increase grade III + IV | |
Birnbaum et al. [133] | 2010 | Phase I | 32 | LA-HNSCC | 66-72 Gy, Ind. Cetux + Carbo/Tax/Cetux concomitant | 3% grade III allergic reaction, 3% grade IV metabolic symptom, 69% grade III + IV mucositis, 3% grade IV dysphagia, 59% pts grade III + IV skin toxicity | |
Jensen et al. [134] | 2011 | Phase II | 30 | NSCLC | 66 Gy (IMRT) | Pulmonary embolism 3% grade III + 3% grade V endocarditis and myocardial infarction grade V each 3%, 13% grade III/IV pneumonia esophagitis, diarrhea, DVT, exacerbation of COPD, urosepsis, pericardial effusion, pneumonitis grade III each 3% | |
Ruhstaller et al. [135] | 2011 | Phase IB/II | 28 | Esophageal cancer | Induction ChTx Cis/docetaxel + neoadjuvant RCh-immunotherapy | 25% grade III/IV esophagitis, 4% grade III/IV rash | |
Pfister et al. [136] | 2006 | Phase I | 22 | LA-HNSCC | 70 Gy RT + Cisplatin | Study closed due to significant AEs. Grade V pneumonia and one death of unknown cause, Grade IV: MI 5%, arrhythmia 5%, metabolic 5%, infection 5% | |
Hofheinz et al. [137] | 2006 | Phase I | 20 | Rectal cancer | Capecitabine + Irinotecan + 50.4 Gy | No grade IV, no rash, 20% grade III diarrhea | |
Kuhnt et al. [138] | 2010 | Phase I | 18 (16 eligible) | LA-HNSCC | HART (70.6 Gy) + Cis | 56% grade III mucositis, 38% ≥ grade III radiodermatitis, 25% ≥ grade III neutropenia, 6% grade III rash | |
Pryor et al. [22] | 2009 | Prospective | 13 | HNSCC | 70 Gy | 46% ≥ grade III acneiform rash, 77% ≥ grade III dermatitis | |
Hughes et al. [29] | 2008 | Phase I | 12 | NSCLC | 64 Gy | Grade III fatigue, pneumonitis each 8% Grade V Infection 8% | |
Zwicker et al. [139] | 2011 | Phase II | 10 | HNSCC | IMRT 50.4 Gy Re-RT + Cetux | 10% grade V mucositis, 10% grade III mucositis, 10% grade IV erythema (20% grade III), 20% grade III acneiform rash | |
Jensen et al. [140] | 2010 | prospective | 9 | Adenoid cystic carcinoma of HN | 5/9: re-RT: median 50,4 Gy, median 65 Gy otherwise (IMRT or C-12 boost) | Grade III Mucositis and Grade III Dysphagia | |
Balermpas et al. [141] | 2009 | Prospective | 7 | HNSCC | Re-irradiation 50,4 Gy-54,0 Gy | New acute side effects: Grade III: pain 14%, mucositis 71%. Dysphagia 57%. Xerostomia 14%. Fibrosis 14%, acneiform rash 29%. | |
Berger et al. [19] | 2008 | Case report | 1 | HNSCC | 72 Gy., regimen change to cetuximab from 5-FU/MMC | Grade IV Dermatitis | |
Trastuzumab | Halyard et al. [48] | 2009 | Phase III | 1503 | Breast cancer | Median 50,4 Gy, previous OP + ChTx | Skin toxicity grade III: 4% (simultaneous) -6% (adjuvant), cardiac events 2% (simultaneous)-3% (adjuvant) |
Belkacemi et al. [49] | 2008 | Multicentric study | 146 | Breast cancer | Median 50 Gy | > grade II esophagitis (12%), 1 pt grade III esophagitis, 5% grade III dermatitis, ≥ grade II LVEF (10%) | |
Caussa et al. [142] | 2011 | Prospective | 106 | Breast cancer | 50 Gy (2 Gy) + 16 Gy boost | 2% grade III skin reaction, 1% grade III esophagitis | |
Anderson [143] | 2009 | Matched case control study | 85 | Breast cancer | n. r. | Grade III dermatotoxicity 2%, 1% ≥ grade II LVEF decrease (reversible) | |
Shaffer et al. [50] | 2009 | retrospective | 44 | Breast cancer | 40-50.4 Gy | In 14% stopped because of cardiac toxicity | |
Chargari et al. [144] | 2011 | Phase I | 31 | Brain mets breast cancer | 30 Gy (3 Gy) WBRT | No grade > II | |
Horton et al. [145] | 2010 | Phase II | 12 | Locally recurrent breast cancer | 50 Gy, ChTx refractory | 17% grade III skin toxicity, 8% grade III lymphopenia, no cardiac toxicity | |
Panitumumab | Pinto et al. [35] | 2011 | Phase II | 60 | Rectal cancer | 5-fluorouracil-oxaliplatin + RT | Grade 3-4 toxicity: diarrhea (39%, one toxic death), cutaneous reactions (19%), nausea, neutropenia (2%), others. |
Wirth et al. [34] | 2010 | Phase I | 19 | LA-HNSCC | 70 Gy + Carbo/Tax (2 Gy) IMRT | 1 pt grade III febrile neutropenia, 84% grade III + IV mucositis, 95% grade III dysphagia, 42% grade III dermatitis, 11% grade III rash, 21% grade III nausea | |
Nimotuzumab (h-R3) | Rodriguez et al. [38] | 2010 | Prospective randomized | 106 | HNSCC | n. r. | III/IV not reported |
Crombet et al. [146] | 2004 | Phase I | 24 | HNSCC | 66 Gy (2 Gy) | 4% grade III somnolence, 13% grade III dysphagia, 21% grade III mucositis, 13% grade III dermatitis, 4% grade III laryngitis | |
Bebb et al. [39] | 2011 | Phase I | 18 | NSCLC | 36/30 Gy (3 Gy) | 50% grade III + IV | |
Choi et al. [40] | 2010 | Phase I | 15 | NSCLC | 36/30 Gy (3 Gy) | 7% grade IV febrile neutropenia/pneumonia, 40% grade III lymphopenia |
Panitumumab
Nimotuzumab
Anti -Her2/neu antibody trastuzumab
Bevacizumab
Substance | Author(s) | Year | Study type | N | tumour | RT dose/ChTx/technique | Toxicity |
---|---|---|---|---|---|---|---|
Bevacizumab | Vredenburgh et al. [147] | 2010 | 125 | Glioblastoma | 59,4 Gy/Temozolomide | Grade III Thromboembolic events: 2% | |
Crane et al. [63] | 2009 | Phase II | 82 | Pancreatic Cancer | 50,4 Gy/Capecitabine | Toxicities possibly attributable to bevacizumab: GI bleeding: 6%. (d83,127,179, 180, 316); grade III, IV, V GI perforation: 4%. (d195,231,286) DVT grade III + IV: 4%; grade III hypertension: 2%; | |
Lai et al. [72] | 2010 | Phase II | 70 | Glioblastoma | 60 Gy/Temozolomide | Grade IV cerebrovascular ischemia: 9%; Grade III+IV CNS hemorrhage: 3%; Grade III+IV GI bleeding/perforation 6%; grade IIII Optic neuropathy: 1%. Grade III+IV venous Thrombosis/PE: 19%. | |
Crane et al. [62] | 2006 | Phase I | 48 | Pancreatic Cancer | 50,4 Gy/Capecitabine | Toxicities possibly attributable to bevacizumab: grade III+V ulceration with bleeding in RT field: 8%. (retrospectively fistulous connection identified in 4%) Grade III GI perforation: 4%; bleeding outside field): 4%; grade III hypertension: 2%. | |
Seiwert et al. [148] | 2008 | Phase I | 43 | Head & Neck | 63-72 Gy/5-FU and Hydroxyurea | Grade V bleeding events: 5%; grade V infection/sepsis: 7%, 2% unknown cause of death; grade III+ Thromboembolic events: 5% DVT, 2% stroke (leading to fatal sepsis, see above); fistula (due to radionecrosis or residual tumour): 12%. Tissue necrosis 9%. | |
Spigel et al. [149] | 2009 | Phase II | A 29 B 5 | SCLC | 61,2 Gy/Carboplatin/Irinotecan (A-limited stage B-locally advanced) | A Grade IV+V tracheoesophageal fistula: 7%. Grade V aerodigestive hemorrhage. B Grade III tracheoesophageal fistula: 40%. Both studies closed due to toxicity. | |
Willet et al. [58] | 2009 | Phase II | 32 | Rectal Cancer | 50,4 Gy//5-FU | Grade III toxicities: GI abscess 3%, Hypertension 9%, radiation dermatitis: 6%; wound separation 3%. No grade IV. | |
Dipetrillo et al. [55] | 2012 | Phase I | 26 | Rectal Cancer | 50,4 Gy/FOLFOX | Grade III + IV Diarrhea: 42%; Bleeding (g3): 4%; g3 neuropathy: 4%; Radiation dermatitis G3: 8%; postoperative wound complications: 35%-the study was discontinued due to this toxicity. | |
Crane et al. [53] | 2010 | Phase II | 25 | Rectal Cancer | 50,4 Gy/Capecitabine | grade III perianal desquamation: 4%; 12% major surgical complications such as anastomotic dehiscence (4%), wound dehiscence (8%) | |
Gutin et al. [68] | 2009 | Phase I | 25 | Glioblastoma/Anaplastic Gliomas | 30 Gy/5 × 6 Gy | Grade IV Gastrointestinal bleeding: 4%, bowel perforation: 4%, wound healing complication: 4%. Grade III CNS hemorrhage: 4%. | |
Koukourakis et al. [59] | 2009 | Phase I/II | 22 | Rectal Cancer | 15 × 3,4 Gy/amifostine, capecitabine | Fistula: 9%, grade IV skin necrosis 5%. | |
Niyazi et al. [69] | 2010 | Retrospective | 20 | Recurrent Glioblastoma | 36 Gy | Grade IV wound healing complication: 5%. grade III DVT: 5%. | |
Koukourakis et al. [150] | 2011 | Phase II | 19 | Rectal cancer | 10 × 3, 4 Gy Amifostine/Capecitabine | Grade III diarrhea: 11%. | |
Goyal et al. [65] | 2010 | Retrospective | 14 | Breast cancer | 50 Gy + 10 Gy | No Grade III/IV toxicity (only acute toxicity assessed) | |
Czito et al. [61] | 2007 | Phase I | 11 | Rectal Cancer | 50,4 Gy/Oxaliplatin + Capecitabine | No grade III + toxicities attributable to bevacizumab: grade III-IV diarrhea: 27%, | |
Resch et al. [151] | 2011 | Phase II | 8 | Rectal cancer | 45 Gy/Capecitabine | Discontinued due to tox after 8 Pt., Grade III GI bleeding: 25%, Grade III diarrhea: 25% | |
Kelly et al. [71] | 2010 | Case reports | 3 | Glioblastoma | Optic neuropathy | ||
Vargo et al. [152] | 2011 | Case report | 1 | Glioblastoma | Dural venous thrombosis |
Anti CD20 monoclonal antibody-rituximab
Small molecules/tyrosine-kinase inhibitors (TKI's)
Substance | Author(s) | Year | Study type | N | tumour | RT dose/ChTx/technique | Toxicity |
---|---|---|---|---|---|---|---|
Sunitinib | Chi et al. [153] | 2010 | Phase II | 23 | HCC | 52.5 (15 Fx) IMRT/3D-CT | 9% grade III upper GI bleeding, 4% hepatitis grade III/4% grade III pancreatitis, 26% grade III + IV thrombopenia, 4% grade III leukopenia |
Stähler et al. [154] | 2010 | Prospective, non-randomized | 22 | RCC (all sites) | Median 40 Gy (median 8 Fx) | 5% grade IV hypertension, 14% grade III + IV nausea | |
Kao et al. [80] | 2009 | Phase I | 21 | Oligometastases | 40-50 Gy (10 Fx) | 62% grade III + IV lymphopenia, 19% grade III neutropenia, 14% grade III + IV thrombopenia, 5% grade III rectal bleeding | |
Hui et al. [155] | 2010 | Phase II | 13 | Nasopharyngeal carcinoma | Sunitinib after RT (60-70 Gy) and multiple Chx | 15% fatal hemorrhages, 31% Grade IV hemorrhages, (among other toxicities) | |
sorafenib | Peters et al. [77] | 2008 | Case study | 1 | RCC | 8 Gy single dose | Grade V bowel perforation (stopped two days before, three days later recommenced) |
lapatinib | Harrington et al. [156] | 2009 | Phase I | 31 | LA-HNSCC | 66-70 Gy + CisPt | 35% grade III mucositis, 19% grade III dermatitis, 13% grade III + IV lymphopenia, 6% grade III neutropenia |
gefitinib | Cohen et al. [157] | 2010 | Phase I | 69 | LA-HNSCC | IC Carbo/Tax, hydroxyurea + 5-FU, 2 × 1.5 Gy/d | 29% grade III + IV neutropenia, 86% grade III + IV mucositis, 33% grade III + IV dermatitis, 3% grade V infections, 17% grade III + IV infections, 4% grade III rash, 3% grade III neurotoxicity |
Pollack et al. [158] | 2011 | Phase II | 43 | Brainstem glioma in children | 55,8 Gy | Grade III+IV: lymphopenia (21%), neutropenia (2%), GI (12%), infection (7%), n, pulmonary (5%), renal, skin (2%), metabolic (2%), intratumoral hemorrhage: 7%. | |
Valentini et al. [159] | 2008 | Phase I/II | 41 | Rectal cancer | 45 Gy + 5.4 Gy + 5-FU | 20% grade III + IV GI toxicity, 15% grade III + IV skin toxicity, 39% grade III + IV hepatic toxicity, 10% grade III + IV GU toxicity, 7% other toxicities grade III + IV | |
Wang et al. [160] | 2011 | Prospective | 26 | Stage III/IV NSCLC | Median 70 Gy | Grade IV leukopenia 4%, grade IV thrombopenia 8%, grade III esophagitis 4%, grade III pneumonitis 4% | |
Zhang et al. [161] | 2009 | Phase I | 24 | NSCLC | 54-60 Gy | 4% grade III nausea | |
Chen et al. [162] | 2007 | Phase I | 23 | HNSCC | Up to 72 Gy | 13% grade III dermatitis, 57% grade III + IV mucositis, 39% grade III + IV dysphagia, 17% grade III + IV diarrhea, 30% grade III + IV neutropenia, 9% grade III + IV anemia, 4% grade IV tumour hemorrhage, 4% grade III GI bleeding | |
Maurel et al. [163] | 2006 | Phase I | 18 | Pancreatic cancer | 45 Gy | No DLT, 11% grade III + IV neutropenia, 6% anemia grade III | |
Czito et al. [164] | 2006 | Phase I | 16 | Pancreatic + rectal cancer | 50.4 Gy (1.8 Gy) + capecitabine | 31% grade III + IV diarrhea | |
Center et al. [165] | 2010 | Phase I | 16 | NSCLC | 70 Gy 3D-CT + docetaxel | 27% grade III + IV hematotoxicity, 27% grade III + IV esophagitis, 20% grade III + IV pulmonary toxicity | |
Schwer et al. [166] | 2008 | Phase I | 15 | Malignant glioma | SRS 18-36 Gy | No DLT, no grade > II | |
Olsen et al. [167] | 2009 | Phase I | 12 | Pancreatic cancer | 50.4 Gy (1.8 Gy) | 45% grade III nausea | |
erlotinib | Brown et al. [168] | 2008 | Phase I/II | 79 | GBM | 60 Gy + TMZ | 18% grade III/IV rash, 16% grade III/IV fatigue, 24% grade III/IV thrombopenia, 4% grade III nausea, 8% grade III diarrhea, 28% grade III/IV leukopenia, 3% grade III anorexia, 18% grade III/IV neutropenia, 6% grade III anemia, 14% grade III lymphopenia, 1% grade V infection without neutropenia, 5% grade III infection without neutropenia, 6% grade III/IV dyspnea, 1% grade III/IV keratitis, 1% grade V pneumonitis, 6% grade III/IV pneumonitis |
Prados et al. [169] | 2009 | Phase II | 65 | GBM | 59.4 Gy/60 Gy + TMZ | 43% grade III lymphopenia, 3% grade IV neutropenia, 2% grade IV thrombopenia, 8% grade III/IV fatigue, 2% grade III diarrhea, 6% grade III rash | |
Herchenhorn et al. [170] | 2010 | Phase I/II | 37 | LA-HNSCC | 70 Gy + Cis | No DLT | |
Choong et al. [171] | 2008 | Phase I | 34 | NSCLC Stage III | 66 Gy (2 Gy), Arm A: Erlotinib + Cis/Eto, Arm B: Induction Carbo/Tax, Carbo/Tax + Erlotinib | 41% grade III + IV WBC, 32% grade III + IV neutropenia, 21% grade III + IV thrombopenia, 26% grade III + IV esophagitis, 3% grade III + IV vomiting, 6% grade III + IV diarrhea, 3% grade III/IV pneumonitis/ototoxicity | |
Peereboom et al. [172] | 2010 | Phase II | 27 | GBM | 60 Gy + TMZ | 7% grade V febrile neutropenia, 4% grade V sepsis without neutropenia, 4% grade V PCP, a pt grade III neutropenia, 15% grade III neutropenia, 30% grade III + IV thrombopenia, 56% pts grade III lymphopenia, 15% grade III + IV anemia, 7% grade III fatigue | |
Chang et al. [173] | 2011 | Retrospective | 25 | NSCLC | 40-50 Gy | 4% grade III rash, 4% grade III diarrhea/esophagitis/anemia, 8% grade III neutropenia/thrombopenia, 8% grade V pneumonitis, 4% grade III pneumonitis | |
Li et al. [174] | 2010 | Phase II | 24 | LA esophageal cancer | 60 Gy + Carbo/Tax | 17% ≥ grade III leukopenia, 8% thrombopenia ≥ grade III | |
Broniscer et al. [175] | 2009 | Phase I | 23 | GBM | 54-59.4 Gy | 39% grade III + IV lymphopenia, 4% grade III rash, 4% grade III diarrhea | |
Robertson et al. [176] | 2009 | Phase I | 22 | Pancreatic cancer | Gem weekly, 30-38 Gy | 5% grade III vomiting/fatigue/nausea, 5% grade III vomiting/diarrhea/nausea, 9% grade IV fatigue | |
Duffy et al. [177] | 2008 | Phase I | 20 | Pancreatic cancer | 50.4 Gy + Gem | 100% grade III lymphopenia, 25% grade III thrombopenia, 30% grade III neutropenia, 5% grade IV neutropenia, 10% grade III anemia, 5% grade III fatigue, 15% grade III diarrhea, 10% grade III rash | |
Krishnan et al. [178] | 2006 | Phase I | 20 | GBM | 60 Gy | 15% grade III stomatitis, 5% grade III fatigue/diarrhea | |
Iannitti et al. [179] | 2005 | Phase I | 17 | LA Pancreatic cancer | 50.4 Gy + Tax/Gem | 6% grade III nausea/fatigue/rash/small bowel stricture/thrombopenia (each), 18% grade III dehydration/thrombosis, 12% grade III diarrhea/hypersensitivity, 6% grade IV neutropenia | |
Nogueira-Rodrigues et al. [180] | 2008 | Phase I | 15 | LA cervical cancer | 45 Gy + brachyTx + CisPt | 7% grade IV hepatotoxicity, 7% grade III dermatitis, 20% III diarrhea, 13% grade III rash | |
Arias de la Vega et al. [181] | 2011 | Phase I | 13 | LA-HNSCC | 63 Gy + Cis adjuvant | Grade III/IV: Mucositis 54%, Asthenia 15%, skin 23%, diarrhea 15%. | |
Lind et al. [182] | 2009 | Phase I | 11 | NSCLC, brain metastases | WBRT (30 Gy) | 9% grade III rash/fatigue | |
Dobelbower et al. [183] | 2006 | Phase I | 11 | Esophageal cancer | 50.4 Gy + 5-FU | 36% pts grade III + IV leukopenia, 9% grade III anemia, 9% grade III thrombopenia, 18% grade III + IV neutropenia, 27% grade III dehydration, 9% grade III nausea, 9% grade III/9% grade IV esophagitis | |
Silvano et al. [82] | 2008 | Case report | 1 | NSCLC | 2 × 8 Gy | Death caused by fatal diarrhea | |
Huang et al. [184] | 2008 | Case study | 1 | NSCLC | WBRT 37.5 Gy | Death caused by exacerbated radiodermatitis and subdural hemorrhage | |
mTOR inhibitors (Sirolimus) | Sarkaria et al. [185] | 2007 | Phase I | 7 | NSCLC | 60 Gy + CisPt weekly | 14% grade III dysphagia, esophagitis, febrile neutropenia, pneumonia |
Bourgier et al. [186] | 2011 | Case reports | 3 | Breast/prostate/ovary cancer | 45 Gy/70 Gy, later | Gastrointestinal radiation recall syndrome with everolimus/temsirolimus |
mTOR inhibitors
Lenalidomide/thalidomide
Substance | Author(s) | Year | Study type | N | tumour | RT dose/ChTx/technique | Toxicity |
---|---|---|---|---|---|---|---|
Thalidomide | Knisely et al. [93] | 2008 | Phase III | 332 (90 thalidomide) | Brain metastases | 37,5 Gy (2,5 Gy) | 53% interruptions because of side-effects |
Chang et al. [187] | 2004 | Phase II | 67 | GBM | 60 Gy (2 Gy), TMZ concomitant | 10% grade III + IV neutropenia, 1% grade V; 16% grade III + IV thrombopenia, 9% grade III + IV rash, 1% grade III constipation, 9% grade III fatigue | |
Atkins et al. [188] | 2008 | Phase II | 39 | CNS metastases (melanoma) | 30 Gy (3 Gy) WBRT + TMZ concomitant | 10% grade III + IV + V thrombosis, 5% grade III + IV + V myelosuppression, 8% grade III + IV + V cardiac events | |
Ch'ang et al. [189] | 2011 | Phase II | 24 | HCC | 50 Gy (2 Gy) | 54% rash, 38% somnolence, 33% constipation | |
Turner et al. [97] | 2007 | Phase II | 13 | Brainstem glioma + GBM | 55.8 Gy (1.8 Gy) | 8% grade IV DVT, ≥ 15% grade III leukopenia/motoneuropathy/constipation | |
Lenalidomide | Drappatz et al. [101] | 2009 | Pilot study | 23 | GBM | 60 Gy (2 Gy) | 4% grade IV pneumonitis/hypoxia, 9% grade III nausea, 4% grade IV pulmonary embolism, 4% grade III pneumonia |