Cetuximab, bevacizumab, and irinotecan for patients with primary glioblastoma and progression after radiation therapy and temozolomide: a phase II trial

TY - JOUR

T1 - Cetuximab, bevacizumab, and irinotecan for patients with primary glioblastoma and progression after radiation therapy and temozolomide

T2 - a phase II trial

AU - Hasselbalch, Benedikte

AU - Lassen, Ulrik

AU - Hansen, Steinbjørn

AU - Holmberg, Mats

AU - Sørensen, Morten

AU - Kosteljanetz, Michael

AU - Broholm, Helle

AU - Stockhausen, Marie-Thérése

AU - Poulsen, Hans Skovgaard

PY - 2010/5

Y1 - 2010/5

N2 - The aim of this clinical trial was to investigate safety and efficacy when combining cetuximab with bevacizumab and irinotecan in patients with recurrent primary glioblastoma multiforme (GBM). Patients were included with recurrent primary GBM and progression within 6 months of ending standard treatment (radiotherapy and temozolomide). Bevacizumab and irinotecan were dministered IV every 2 weeks. The first 10 patients received bevacizumab 5 mg/kg, but this was increased to 10 mg/kg after interim safety analysis. Irinotecan dose was based on whether patients were taking enzyme-inducing antiepileptic drugs or not: 340 and 125 mg/m2, respectively. Cetuximab 400 mg/m2 as loading dose followed by 250 mg/m2 weekly was administered IV. Forty-three patients were enrolled in the trial, of which 32 were available for response. Radiographic responses were noted in 34%, of which 2 patients had complete responses and 9 patients had partial responses. The 6-month progression-free survival probability was 30% and median overall survival was 29 weeks (95% CI: 23-37 weeks). One patient had lacunar infarction, 1 patient had multiple pulmonary embolisms, and 3 patients had grade 3 skin toxicity, for which 1 patient needed plastic surgery. One patient was xcluded due to suspicion of interstitial lung disease. Three patients had deep-vein thrombosis; all continued on study after adequate treatment. Cetuximab in combination with bevacizumab and irinotecan in recurrent GBM is well tolerated except for skin toxicity, with an encouraging response rate. However, the efficacy data do not seem to be superior compared with results with bevacizumab and irinotecan alone.

AB - The aim of this clinical trial was to investigate safety and efficacy when combining cetuximab with bevacizumab and irinotecan in patients with recurrent primary glioblastoma multiforme (GBM). Patients were included with recurrent primary GBM and progression within 6 months of ending standard treatment (radiotherapy and temozolomide). Bevacizumab and irinotecan were dministered IV every 2 weeks. The first 10 patients received bevacizumab 5 mg/kg, but this was increased to 10 mg/kg after interim safety analysis. Irinotecan dose was based on whether patients were taking enzyme-inducing antiepileptic drugs or not: 340 and 125 mg/m2, respectively. Cetuximab 400 mg/m2 as loading dose followed by 250 mg/m2 weekly was administered IV. Forty-three patients were enrolled in the trial, of which 32 were available for response. Radiographic responses were noted in 34%, of which 2 patients had complete responses and 9 patients had partial responses. The 6-month progression-free survival probability was 30% and median overall survival was 29 weeks (95% CI: 23-37 weeks). One patient had lacunar infarction, 1 patient had multiple pulmonary embolisms, and 3 patients had grade 3 skin toxicity, for which 1 patient needed plastic surgery. One patient was xcluded due to suspicion of interstitial lung disease. Three patients had deep-vein thrombosis; all continued on study after adequate treatment. Cetuximab in combination with bevacizumab and irinotecan in recurrent GBM is well tolerated except for skin toxicity, with an encouraging response rate. However, the efficacy data do not seem to be superior compared with results with bevacizumab and irinotecan alone.

KW - Adult

KW - Aged

KW - Antibodies, Monoclonal

KW - Antibodies, Monoclonal, Humanized

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Bevacizumab

KW - Brain Neoplasms

KW - Camptothecin

KW - Cetuximab

KW - Combined Modality Therapy

KW - Dacarbazine

KW - Disease-Free Survival

KW - Female

KW - Glioblastoma

KW - Humans

KW - Immunohistochemistry

KW - Kaplan-Meier Estimate

KW - Male

KW - Middle Aged

KW - Neoplasm Recurrence, Local

KW - Salvage Therapy

KW - Young Adult

KW - Clinical Trial, Phase II

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1093/neuonc/nop063

DO - 10.1093/neuonc/nop063

M3 - Journal article

C2 - 20406901

SN - 1522-8517

VL - 12

SP - 508

EP - 516

JO - Neuro-Oncology

JF - Neuro-Oncology

IS - 5

ER -