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

Abstract

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 administered 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/m(2), respectively. Cetuximab 400 mg/m(2) as loading dose followed by 250 mg/m(2) 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 excluded 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.

Radiotherapy plus nimotuzumab or placebo in the treatment of high grade glioma patients: results from a randomized, double blind trial

“…Several EGFR inhibitors have been used to treat HGG patients [29-42]. Cetuximab was administered as monotherapy to recurrent glioma patients with an acceptable safety profile [30].…”

Bevacizumab for the Treatment of Glioblastoma

“…Bevacizumab in combination with other cytotoxic drugs or targeted agents both in newly diagnosed and recurrent GBM has been tested in phase II trials. Trials with bevacizumab plus erlotinib,42 etoposide,43 temozolomide,44 fotemustine,45 cetuximab,46 or carboplatin (AUC 4–6 mg/mL/min) every 28 days have been reported 47. All these regimens were associated with a similar PFS benefit and a similar radiographic RR when compared with historical bevacizumab alone or bevacizumab plus irinotecan regimens (see Table 2).…”

Antibody, T-cell and Dendritic Cell Immunotherapy for Malignant Brain Tumors

“…Several EGFR-specific mAbs have been generated for targeting EGFR-overexpressing tumors [26]. The anti-EGFR mAb, cetuximab (IMC-C225; Erbitux ® , ImClone Systems, NJ, USA) was tested individually and in combination with bevacizumab and irinotecan for recurrent HGG patients; a median OS of 5–7 months was achieved [27,28]. Interestingly, the response rate with the addition of cetuximab does not seem to be superior compared with that of single-agent bevacizumab (historical data median OS: 9.7 months [29]) or bevacizumab plus irinotecan (historical data median OS: 8.9 months [29]).…”