Infusional Vinorelbine in Relapsed or Refractory Lymphomas

Abstract

Vinorelbine (Navelbine™) is i. semisynthetic vinca alkaloid devoid ot serious neurotoxicity. When given weekly vinorelbine has documented activity against many tumors, including lymphomas. Since weekly schedules cannot be easily incorporated in combination regimens, we tested an infusional schedule of vinorelbine given every 21 days in adults with relapsed or refractory lymphoma. Patients with inadequate organ or bone marrow reserve. HIV or other 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/m², followed by intravenous continuous infusion over 24 hours daily for four days increasing from 10, 12, to 14 mg/m²/d in successive three-patient cohorts. Cycles were repeated every 21 days, and the daily continuous infusion dose was adjusted for toxicity. Dose-limiting mucositis and neutropenia were reached at the continuous dose of 14 mg/m²/d. Consequently, for the Phase II trial the starting continuous infusion dose was 12 mg/m²/d. After the first 19 patients were entered in the phase II study, the starling infusion dose was reduced to 10 mg/m²/d because of frequent grade 3/4 myelosuppression and mucositis. Forty-four patients were entered in the phase II study, of whom 41 are evaluable. 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 Disease in lone patient. The median number of prior regimens was 3 (range 1-11). The lymphoma was refractory to the initial regimen in nine patients, and to the regimen immediately before vinorelbine in 20 patients. Serum LDH was high in 21/41, and serum β2-microglobulin > 3.0 mg / L in 16/31 patients. 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 were administered. Neutrophil nadir was < 1000/μml1 in 65% and < 100/μml1 in 35% of courses, respectively. Platelet nadir was < :100,000/μml1 in 30% and < 20,000/μml1 in 8% of courses, respectively, Grade 3/4 mucositis was seen 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 vinorelbine has modest activity in patients with relapsed or refractory NHL. Myelosuppression is frequent but reversible, but there is, no significant neurotoxicity. The role of