Phase I evaluation of prolonged-infusion gemcitabine with irinotecan for relapsed or refractory leukemia or lymphoma

Purpose: To estimate the maximum-tolerated duration of infusion of gemcitabine at 10 mg/m(2)/min in combination with irinotecon at 40 mg/m(2) daily for 3 days in the treatment of relapsed or refractory acute leukemia or lymphoma. Patients and Methods: Patients with leukemia or lymphoma were escalated in separate strata. Stratum I consisted of 11 patients, median age of 47 years (range, 18 to 68 years), with relapsed or refractory leukemia. Stratum 11 contained nine patients, median age of 48 years (range, 39 to 68 years), who had refractory non-Hodgkin's lymphoma. Patients received irinotecan at 40 mg/m(2) daily for 3 days, beginning just before the first dose of gemcitabine. Gemcitabine was given at 10 mg/m(2)/min, with the total duration adjusted following a modified continuous reassessment model. Results: Severe myelosuppression and stomatitis/esophogitis were the most serious hematologic and nonhematologic toxicities. Several patients developed febrile neutropenia, nausea, or vomiting. In both strata, the maximum recommended duration of infusion of gemcitabine was 12 hours delivered at 10 mg/m(2)/min (7,200 mg/m(2)). The overall response rate for one cycle of this therapy in this phase I trial for patients with leukemia was 18% (95% confidence interval, 8% to 45%), and for these with lymphoma, 33% (95% confidence interval, 17% to 66%). Conclusion: A prolonged infusion of gemcitabine at 10 mg/m(2)/min for 12 hours with 3 days of irinotecon at 40 mg/m(2)/d is a tolerable induction regimen for patients with acute leukemia or lymphoma. Stomatitis/esophagitis should be anticipated; however, this regimen may induce responses in patients with difficult-to-treat hematologic malignancies. (C) 2002 by American Society of Clinical Oncology.