ARTICLE ABSTRACT
Purpose:
Treatment of advanced pancreatic cancer with a single therapeutic at a maximal dose has been largely ineffective at increasing survival. Combination therapies are commonly studied but often limited by toxicity. We previously showed that low-dose multi-agent therapy with gemcitabine, docetaxel (taxotere), capecitabine (xeloda) and cisplatin (GTX-C) was safe, well-tolerated and effective. Here, we hypothesize that adding irinotecan to GTX-C may improve survival with minimal toxicity.
Patients and Methods:
Patients with treatment-naïve metastatic pancreatic adenocarcinoma were treated with GTX-CI. Treatment consisted of capecitabine 500 mg BID on days 1-14 and gemcitabine 300 to 500 mg/m2, docetaxel 20 mg/m2, cisplatin 15 to 20 mg/m2 and irinotecan 20 to 60 mg/m2 on days 4 and 11 of a 21-day cycle. The primary objective was nine-month overall survival (OS). Secondary objectives included response rate (RR), disease control rate (DCR), progression free survival (PFS) and OS.
Results:
The regimen was well-tolerated. The recommended phase 2 dose was gemcitabine 500mg/m2, docetaxel 20mg/m2, capecitabine 500 mg/m2, cisplatin 20mg/m2 and irinotecan 20mg/m2. Median follow-up in phase II was 11.02 months (2.37 -45.17). Nine-month OS rate was 57% (95% CI: [41%, 77%]. RR was 57% (95% CI: [37%, 75%] 50% PR and 7% CR). DCR was 87% (95% CI: [69%, 96%]). Median OS and PFS were 11.02 (95% CI: [8.54, 21.09]) and 8.34 (95% CI: [6.34, NA]) months, respectively.
Conclusions:
The addition of irinotecan to GTX-C was safe and well-tolerated. While the study did not meet its primary objective, the responses were clinically meaningful using a well-tolerated regimen.
