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Phase 2 study of carboplatin, irinotecan, and bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy
Author(s) -
Reardon David A.,
Desjardins Annick,
Peters Katherine B.,
Vredenburgh James J.,
Gururangan Sridharan,
Sampson John H.,
McLendon Roger E.,
Herndon James E.,
Coan April,
Threatt Stevie,
Friedman Allan H.,
Friedman Henry S.
Publication year - 2011
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.26188
Subject(s) - medicine , bevacizumab , irinotecan , carboplatin , clinical endpoint , regimen , phases of clinical research , progression free survival , surgery , gastroenterology , oncology , toxicity , chemotherapy , cancer , colorectal cancer , clinical trial , cisplatin
BACKGROUND: The efficacy of carboplatin, irinotecan, and bevacizumab among recurrent glioblastoma (GBM) patients after prior progression on bevacizumab therapy in a phase 2, open‐label, single‐arm trial was evaluated. METHODS: Eligible patients received carboplatin (area under the plasma curve [AUC] 4 mg/ml‐min) on day 1, whereas bevacizumab (10 mg/kg) and irinotecan (340 mg/m 2 for patients on CYP3A enzyme‐inducing anti‐epileptics [EIAEDs] and 125 mg/m 2 for patients not on EIAEDs) were administered on days 1 and 14 of every 28‐day cycle. Patients were evaluated after each of the first 2 cycles and then after every other cycle. Treatment continued until progressive disease, unacceptable toxicity, noncompliance, or voluntary withdrawal. The primary end point was progression‐free survival at 6 months (PFS‐6), and secondary end points included safety and median overall survival (OS). RESULTS: All patients had progression on at least 1 prior bevacizumab regimen and 56% enrolled after either second or third overall progression. The median OS was 5.8 months (95% confidence interval [CI], 4.0‐7.0 months) and PFS‐6 rate was 16% (95% CI, 5.0%‐32.5%). The most common grade 3 or 4 events were hematologic and occurred in 29% of cycles. Nine patients (38%) required dose modification. There were no treatment‐related deaths. CONCLUSIONS: Carboplatin, irinotecan, and bevacizumab was associated with modest activity and adequate safety among recurrent GBM patients who progressed on bevacizumab previously. Cancer 2011;. © 2011 American Cancer Society.