Excess toxicity associated with docetaxel and irinotecan in patients with metastatic, gemcitabine-refractory pancreatic cancer: results of a phase II study.

Background: No therapeutic standard of care exists for patients with advanced pancreatic cancer who progress following first-line treatment with a gemcitabine-based regimen. There is evidence of synergistic activity between docetaxel and irinotecan, and the combination of these two agents has shown promising efficacy in the first-line setting for advanced pancreatic cancer. We, therefore, evaluated this regimen in patients with gemcitabine-refractory disease.

Methods: Eligible patients with metastatic pancreatic adenocarcinoma were required to have an elevated serum CA19-9 (> 2x ULN) and exposure to one or two prior chemotherapy regimens, including one gemcitabine-based. Treatment consisted of docetaxel 65 mg/m2 and irinotecan 160 mg/m2, both administered every 21 days. Serum CA19-9 levels were measured at the start of each treatment cycle and CT scans performed after every two cycles.

Results: Fourteen patients were enrolled before the study was closed due to excess toxicity. The most common grade 3/4 toxicities included neutropenia/leukopenia, nausea and vomiting, and diarrhea. Fully half of patients received only 1 treatment cycle, with a median time to treatment failure of 36 days. No objective responses were observed, although 3 patients had stable disease for at least 6 cycles. Overall survival for the entire cohort was 134 days, with a 6-month survival rate of 36%.

Conclusions: The combination of docetaxel and irinotecan given on a 21-day cycle is associated with excess toxicity in gemcitabine-refractory patients with advanced pancreatic cancer. Although select patients may benefit from treatment, the overall risk:benefit ratio is unfavorable, and other dosing regimens and therapeutic options should be explored in this setting.