NCCTG phase II trial of bevacizumab, gemcitabine, oxaliplatin in patients with metastatic pancreatic adenocarcinoma

Abstract

4113 Background: The combination of gemcitabine and oxaliplatin (GemOx) is a highly active regimen in pancreatic cancer. A recent study with the biologic agent, bevacizumab, and gemcitabine has also demonstrated significant activity. A phase II study is ongoing to evaluate whether combining an active cytotoxic doublet with an effective targeted agent improves 6-month survival and is tolerable in previously untreated patients (pts) with metastatic pancreas cancer. Methods: Treatment consists of gemcitabine 1000 mg/m2 IV over 100 minutes and bevacizumab 10 mg/kg IV given on day 1 and 15; oxaliplatin 100 mg/m2 IV is given on day 2 and 16. A treatment cycle consists of 28 days. Eligibility includes: no prior chemotherapy, ECOG PS 0–2, bili < 2× UNL, AST < 5× UNL. Pts with stable full-dose anticoagulation are eligible. Bevacizumab specific exclusions include no recent stroke, heart attack, embolus, tumor invasion or significant proteinuria. CT scans are obtained every 2 cycles. Treatment continues until disease progression, toxicity or patient refusal. Results: Sixty-three patients of a planned 75 were enrolled from 7/05 to 1/06; 2 cycles of toxicity data are available on 31 of the first 32 consecutive pts. The overall grade 3+ toxicity rate is 52% (16/31); more specifically, the grade 3 toxicities were 42% (13/31) and the grade 4 rate is 10% (3/31). Grade 3 adverse events are nausea (4), vomiting (4), alk phos (3), dehydration (3), thrombosis (2), leukopenia (2), neutropenia (4), abdominal pain (2), hypokalemia (4), and one each of the following: anorexia, low consciousness, pneumonia, rectal pain, diarrhea, and proctitis. There was one patient death due to cerebral ischemia (grade 5: 1/31 or 3%). Conclusions: Early assessment of toxicity in this trial reveals a reasonably tolerable regimen. Addition of bevacizumab to GemOx appears to have grade 3/4 toxicity rates similar to historical observations (ECOG 6201). Toxicity data for all patients, after at least 2 cycles of treatment, will be presented. [Table: see text]