Infusional vinorelbine in relapsed or refractory lymphomas

Vinorelbine (Navelbine(TM)) is a semisynthetic vinca alkaloid devoid of ser ious neurotoxicity. When given weekly vinorelbine has documented activity a gainst many tumors, including lymphomas. Since weekly schedules cannot be e asily incorporated in combination regimens, we tested an infusional schedul e of vinorelbine given every 21 days in adults with relapsed or refractory lymphoma. Patients with inadequate organ or bone marrow reserve, HIV or oth er serious infection, central nervous system disease, or prior stem cell or bone marrow transplantation were ineligible. In the phase I part, patients received a constant intravenous bolus of 8 mg/m(2), followed by intravenou s continuous infusion over 24 hours daily for four days increasing from 10, 12, to 14 mg/m(2)/d in successive three-patient cohorts. Cycles were repea ted every 21 days, and the daily continuous infusion dose was adjusted for toxicity. Dose-limiting mucositis and neutropenia were reached at the conti nuous dose of 14 mg/m(2)/d. Consequently, for the Phase II trial the starti ng continuous infusion dose was 12 mg/m(2)/d. After the first 19 patients w ere entered in the phase II study, the starting infusion dose was reduced t o 10 mg/m(2)/d because of frequent grade 3/4 myelosuppression and mucositis . Forty-four patients were entered in the phase II study, of whom 41 are ev aluable. Median age was 61 years, 23 were males, with clinically aggressive non-Hodgkin's lymphoma (NHL) in 22, indolent NHL in 18, and Hodgkin's Dise ase in one patient. The median number of prior regimens was 3 (range 1-11). The lymphoma was refractory to the initial regimen in nine patients, and t o the regimen immediately before vinorelbine in 20 patients. Serum LDH was high in 21/41, and serum beta (2)-microglobulin > 3.0 mg / L in 16/31 patie nts. Responses were observed in four of 22 patients with aggressive NHL (18 %, 95% confidence interval 5%-40%). and in six of 18 with indolent NHL (33% , 95% confidence interval 13%-59%). Median progression-free survival was 6 months for responders. During the Phase II trial 114 vinorelbine courses we re administered. Neutrophil nadir was < 1000/<mu>l in 65% and < 100/<mu>l i n 35% of courses, respectively. Platelet nadir was < 100,000/<mu>l in 30% a nd < 20,000/<mu>l in 8% of courses, respectively. Grade 3/4 mucositis was s een in 18% of courses, and neutropenic fever in 13%. and was complicated by death in one patient. We conclude that this dosage and schedule of vinorel bine has modest activity in patients with relapsed or refractory NHL. Myelo suppression is frequent but reversible, but there is no significant neuroto xicity. The role of vinorelbine in combination regimens for patients with r elapsed lymphomas. particularly those of indolent histology. should be furt her investigated.