Phase i trial of continuously infused gemcitabine with cpt-11 for refractory hematologic malignancies

In vitro modeling suggests additive efficacy of the nucleoside analogue gemcitabine with the topoisomerease inhibitor CPT-11. We are performing a phase I trial for patients with refractory leukemia or lymphoma using 1 cycle of variable durations of infusion of gemcitabine delivered at a rate of 10 mg/sq m/min in combination with CPT-11 40 mg/sq m infused over 90 minutes daily for 3 days, followed by growth factor support. Duration of gemcitabine infusion is varied according to a modified continuous reassessment model with the MTD being the duration at which we estimate 1/3 of patients will experience a DLT. In the NHL strata, a DLT is neutropenia for > 10 days, non-heme grade 4 toxicity for >1 day or grade 3 for > 4 days. In the leukemia strata, a DLT is neutropenia for > 4 weeks (not due to disease), non-heme grade 4 toxicity for >2 days or grade 3 for > 6 days. 12 patients aged 19-69 yo have been treated to date. 3-6 days of myelosuppression is anticipated in the NHL group and 2-4 weeks in the leukemia cohort. Average # 9 hours gem/ 12 hours gem/ 15 hours gem/ Responses prior regimens toxicity toxicity toxicity NHL 4(2-8) 0 3; 1 with grade 2; 1 DLT stomatitis 1PR;3SD;1NR 3 stomatitis x 2d Leukemia 3 (2-6) 2; no DLT 4; 1 with grade 1; no DLT 1PR;2SD 5 tumor lysis, 1 fungal pn Patients in the NHL cohort had low grade or transformed disease. Two had a significant PR, 3 have SD lasting for 1 -2 months after therapy. In the Leukemia cohort, 3/6 évaluable cleared all blasts from the marrow at nadir and at recovery 1 had a PR and 2 had SD. These data suggest the combination is feasible with toxicities similar to other aggressive regimens. The few preliminary responses noted in this refractory group encourage continued investigation with this regimen.

Duke Scholars

Author Carlos Manuel de Castro III Medicine, Hematologic Malignancies and Cellular Therapy

Author Jon Paul Gockerman Medicine, Hematologic Malignancies and Cellular Therapy