Salvage chemotherapy with mitomycin, docetaxel, and irinotecan (MDI regimen) in metastatic pancreatic adenocarcinoma: A phase I and II trial

Background: This study evaluates the maximum tolerated dose (MTD) and activity of mitomycin, docetaxel. and irinotecan (MDI) regimen on metastatic pancreatic adenocarcinoma, previously treated with gemcitabine-containing chemotherapy. Patients and Methods: Patients with less than 76 years, Karnofsky performance status greater than or equal to60, and adequate bone marrow, kidney, and liver function were eligible for this trial. Treatment consisted of mitomycin 6 mg/m(2) day 1, docetaxel and irinotecan on days 2 and 8 with escalating doses, every 4 weeks. Dose levels were level 1:30 and 70 mg/m2; level 2:30 and 100 mg/m(2) level 3:30 and 85 mg/m(2); and level 4:35 and 85 mg/m(2) Dose-limiting toxicity (DLT) was defined as grade 4 neutropenia >7 days, febrile neutropenia, grade 4 thrombocytopenia, nausea and vomiting, or diarrhea, grade greater than or equal to3 nonhematological toxicity, or failure to recover to grade less than or equal to1 toxicity by day 43, occurring during the first cycle of chemotherapy. Results: Between September 2001 and October 2002, 15 eligible patients, three of whom had been previously treated with two lines of chemotherapy, received 33 cycles of MDI. Toxicity consisted of grade 3 to 4 neutropenia in 23% of cycles, fatigue, diarrhea, and vomiting in 10% of cycles, and one toxic death. DLT was observed in 2 of 6 level 2 patients (one toxic death and one grade 3 fatigue), and 2 of 3 level 4 patients (one neutropenic fever and one grade 3 fatigue). Thirteen patients were assessable for response. No objective response was observed among patients treated with MTD or higher doses. Three patients had stable disease; all other patients had progressive disease. The median time to tumor progression and median Survival was 1.7 and 6.1 months, respectively. Conclusion: The MTD was mitomycin 6 mg/m(2) day one, and docetaxel 30 and irinotecan 85 mg/m(2) days 2 and 8. This regimen is inactive in metastatic pancreatic cancer.