Irinotecan/gemcitabine combination chemotherapy in pancreatic cancer

Gemcitabine (Gemzar) and irinotecan (CPT-II, Camptosar) are active cytotoxi c drugs against pancreatic cancer: Preclinical data evaluating the combinat ion of gemcitabine and irinotecan suggest dose-dependent synergistic intera ctions in SCOG small-cell lung cancer and MCF-7 breast cancer cell lines. T wo phase I trials of this combination have been reported to date: the day 1 and 8 every-3-week schedule (IrinoGem trial), and the day 1, 8, and 15 eve ry-4-week schedule (MSKCC trial). Both trials aimed to determine the maximu m tolerated dose of irinotecan when administered as a 90-minute IV infusion either immediately after (IrinoGem) or before or immediately after (MSKCC) gemcitabine at 1,000 mg/m(2) by 30-minute IV infusion lit patients with so lid tumors. The achieved maximum tolerated dose of IrinoGem has a higher do se intensity of irinotecan (100 mg/m(2) on days 1 and 8, every-3-week cycle ) compared with the MSKCC schedule (60 mg/m2 on days 1, 8, and 15, every-4- week trial). In IrinoGem, two of three previously untreated metastatic meta static cancer patients had durable radiologic partial responses. The third had stable disease with clinical benefit for eight cycles. In addition, a p atient with metastatic adenocarcinoma of unknown primary - potentially panc reatic - has had a durable response and is alive more than 30 months after the diagnosis. Preliminary results of a 45-patient multicenter phase II tri al with IrinoGem ill advanced and metastatic pancreas cancer were recently reported. Toxicity was modest with no toxic deaths or neutropenic fever, Ra diologic response rate was 20% of patients (9 out of 45) and a CA 19-9 decr ease of more than 50% from baseline values occurred in 32.5% of patients (1 3 out of 40). Median survival was 6 months (range: 0.9 to 12.2+ months) and median time to treatment failure was 2.9 months (range: 0.1 to 11.3+ month s). A pivotal international multicenter phase III trial comparing IrinoGem to single-agent gemcitabine in advanced and metastatic pancreas cancer is o ngoing.