Table 1 Studies on monoclonal EGFR antibodies
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 |
| Â | Koutcher et al. [24] | 2009 | Retrospective | 115 | LA-HNSCC | 66 Gy/69.96 Gy | 3% grade IV radio-dermatitis, 19% grade III radio-dermatitis |
| Â | Studer et al. [25] | 2011 | Prospective | 99 | HNSCC | 66-70 Gy, 30/99 switch from Cis | 34% grade II/IV dermatitis |
| Â | 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 |
| Â | 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 |
| Â | 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% |
| Â | 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) |
| Â | 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 |
| Â | 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% |
| Â | 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 |
| Â | Buiret et al. [126] | 2010 | Retrospective multicenter | 46 | HNSCC | Ind. ChTx Doc/Cis/5-FU, RIT (70 Gy) | No grade IV toxicity |
| Â | Garcia-Huttenlocher et al. [127] | 2008 | Retrospective | 46 | HNSCC | Median 66 Gy (IMRT) | 20% grade III skin toxicity, 4% grade III mucositis |
| Â | 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 |
| Â | 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%) |
| Â | De Vita et al. [130] | 2011 | Phase II | 41 | Esophageal cancer | Ind. FOLFOX4 + 50.4 Gy/Cetux | 30% grade II/IV skin toxicity/neutropenia |
| Â | 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 |
| Â | Kim et al. [98] | 2011 | Phase II | 40 | Rectal cancer | Capecitabine + Cetux + Irinotecan + 50.4 Gy | 3% grade IV leukopenia, 3% grade III rash |
| Â | 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 |
| Â | 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%. |
| Â | 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%. |
| Â | Heron et al. [132] | 2011 | Matched pair retrospective | 35 | HNSCC | SBRT Re-RT | No significant increase grade III + IV |
| Â | 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 |
| Â | 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% |
| Â | 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 |
| Â | 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% |
| Â | 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 |
| Â | Hughes et al. [29] | 2008 | Phase I | 12 | NSCLC | 64 Gy | Grade III fatigue, pneumonitis each 8% Grade V Infection 8% |
| Â | 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 |
| Â | 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 |
| Â | 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%. |
| Â | 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%) |
| Â | 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) |
| Â | Shaffer et al. [50] | 2009 | retrospective | 44 | Breast cancer | 40-50.4 Gy | In 14% stopped because of cardiac toxicity |
| Â | Chargari et al. [144] | 2011 | Phase I | 31 | Brain mets breast cancer | 30 Gy (3 Gy) WBRT | No grade > II |
| Â | 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. |
| Â | 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 |
| Â | 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 |
| Â | Bebb et al. [39] | 2011 | Phase I | 18 | NSCLC | 36/30 Gy (3 Gy) | 50% grade III + IV |
| Â | Choi et al. [40] | 2010 | Phase I | 15 | NSCLC | 36/30 Gy (3 Gy) | 7% grade IV febrile neutropenia/pneumonia, 40% grade III lymphopenia |