A phase II study of gemcitabine in patients with relapsed or refractory low-grade non-Hodgkin lymphoma.

PURPOSE: The purpose of this study was to determine the tolerability, clinical response rate, and time to disease progression of gemcitabine treatment in patients with low-grade non-Hodgkin lymphoma. (NHL) PATIENTS AND METHODS: Twenty patients with low-grade NHL and progression of disease after at least 1 prior treatment regimen were prospectively enrolled. The treatment regimen consisted of 1200 mg/m2 gemcitabine intravenously administered weekly for 7 weeks followed by a 1-week rest. Subsequent treatment was given weekly for 3 weeks followed by a 1-week rest and repeated for a maximal treatment of 6 cycles until disease progression or unacceptable toxicity. RESULTS: The predominant histologic subtypes among our patients were small lymphocytic (8 of 20) and follicular (7 of 20). Grade III/IV hematologic toxicity was observed in 15 of 20 patients and dose reductions or treatment delays occurred in 19 of 20 patients. Fatigue and asthenia were treatment-limiting in many patients. There were no complete or partial responses observed and only 2 patients had stable disease after 12 weeks of treatment. The average time to progression or off-study status was 2.3 months (95% confidence interval, 1.7-2.9) with 8 patients showing progression of disease. Twelve patients were taken off the study as a result of unacceptable toxicity before observed progression of disease. No patient completed the planned course of therapy. With a median follow up of 10.2 months, 10 of 20 patients remained alive. CONCLUSION: Gemcitabine as a single agent, in this dosage and schedule, has minimal clinical activity in relapsed or refractory low-grade lymphomas and was associated with considerable toxicity. Therefore, further study of gemcitabine in this setting is not justified.

A randomized controlled trial of darbepoetin alfa administered as a fixed or weight-based dose using a front-loading schedule in patients with anemia who have nonmyeloid malignancies.

BACKGROUND: The effect of using fixed versus weight-based doses for erythropoietic agents has not been reported previously. To investigate this issue, the authors conducted a randomized Phase II study of darbepoetin alfa administered as either a fixed dose or a weight-based dose using an accelerated correction and maintenance dosing regimen (front-loading). METHODS: During the correction phase, patients with anemia (hemoglobin < 11.0 g/dL) who had nonmyeloid malignancies and who were receiving chemotherapy were given darbepoetin alfa at a fixed dose of 325 microg (n = 122) or at a weight-based dose of 4.5 microg/kg (n = 120) once weekly until they achieved a hemoglobin concentration > or = 12.0 g/dL. Patients then received darbepoetin alfa (325 microg or 4.5 microg/kg) once every 3 weeks for the remainder of the 16-week treatment period (maintenance phase). RESULTS: Darbepoetin alfa resulted in high Kaplan-Meier rates of hematopoietic response (> or = 2 g/dL increase from the baseline level or a hemoglobin level > or = 12 g/dL) in both the fixed-dose group (86%; 95% confidence interval [95% CI], 78- 94%) and the weight-based dose group (84%; 95% CI, 76-92%). The median time to hematopoietic response was 34 days (95% CI, 28-44 days) for the fixed-dose group and 36 days (95% CI, 30-45 days) for the weight-based dose group. Hemoglobin concentrations were maintained at target levels for up to 16 weeks in both groups. Darbepoetin alfa was well tolerated, and no clinically significant differences between fixed doses and weight-based doses were observed. CONCLUSIONS: Darbepoetin alfa was effective when administered as either a fixed dose or a weight-based dose using a front-loading approach to rapidly correct anemia and effectively maintain hemoglobin levels in patients with anemia who had malignant disease.