Irinotecan/Gemcitabine Combination Chemotherapy in Pancreatic Cancer

ABSTRACT: Gemcitabine (Gemzar) and irinotecan (CPT-11, Camptosar) areactive cytotoxic drugs against pancreatic cancer. Preclinical data evaluatingthe combination of gemcitabine and irinotecan suggest dose-dependent synergisticinteractions in SCOG small-cell lung cancer and MCF-7 breast cancer cell lines.Two phase I trials of this combination have been reported to date: the day 1 and8 every-3-week schedule (IrinoGem trial), and the day 1, 8, and 15 every-4-weekschedule (MSKCC trial). Both trials aimed to determine the maximum tolerateddose of irinotecan when administered as a 90-minute IV infusion eitherimmediately after (IrinoGem) or before or immediately after (MSKCC) gemcitabineat 1,000 mg/m2 by 30-minute IV infusion in patients with solid tumors. Theachieved maximum tolerated dose of IrinoGem has a higher dose intensity ofirinotecan (100 mg/m2 on days 1 and 8, every-3-week cycle) compared with theMSKCC schedule (60 mg/m2 on days 1, 8, and 15, every-4-week trial). In IrinoGem,two of three previously untreated metastatic pancreas cancer patients haddurable radiologic partial responses. The third had stable disease with clinicalbenefit for eight cycles. In addition, a patient with metastatic adenocarcinomaof unknown primary—potentially pancreatic—has had a durable response and isalive more than 30 months after the diagnosis. Preliminary results of a45-patient multicenter phase II trial with IrinoGem in advanced and metastaticpancreas cancer were recently reported. Toxicity was modest, with no toxicdeaths or neutropenic fever. Radiologic response rate was 20% of patients (9 outof 45), and a CA 19-9 decrease of more than 50% from baseline values occurred in32.5% of patients (13 out of 40). Median survival was 6 months (range: 0.9 to12.2+ months) and median time to treatment failure was 2.9 months (range: 0.1 to11.3+ months). A pivotal international multicenter phase III trial comparingIrinoGem to single-agent gemcitabine in advanced and metastatic pancreas canceris ongoing. [ONCOLOGY 15(Suppl 5):46-51, 2001]

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