Infusional vinorelbine in relapsed or refractory lymphomas

Area of Science:

• Oncology
• Pharmacology

Background:

• Vinorelbine is a semisynthetic vinca alkaloid with known activity against lymphomas.
• Weekly vinorelbine schedules are difficult to incorporate into combination regimens.
• An infusional schedule of vinorelbine every 21 days was investigated for relapsed or refractory lymphoma.

Purpose of the Study:

• To evaluate the safety and efficacy of an infusional schedule of vinorelbine in adults with relapsed or refractory lymphoma.
• To determine the maximum tolerated dose (MTD) of infusional vinorelbine.
• To assess response rates and survival in patients treated with this regimen.

Main Methods:

• Phase I/II clinical trial design.
• Patients received intravenous bolus followed by continuous infusion of vinorelbine every 21 days.
• Dose escalation in Phase I to determine MTD; Phase II evaluated efficacy at a reduced dose.
• Eligibility criteria excluded patients with CNS disease, prior stem cell transplant, or inadequate organ reserve.

Main Results:

• The MTD was determined to be 12 mg/m(2)/day for 4 days, with dose-limiting mucositis and neutropenia observed at 14 mg/m(2)/day.
• Response rates were 18% in aggressive non-Hodgkin's lymphoma (NHL) and 33% in indolent NHL.
• Frequent but reversible myelosuppression and mucositis were observed; no significant neurotoxicity was noted.

Conclusions:

• The tested dosage and schedule of vinorelbine demonstrate modest activity in relapsed or refractory NHL.
• Myelosuppression is a frequent but manageable toxicity.
• Further investigation of vinorelbine in combination regimens for relapsed lymphomas, especially indolent types, is warranted.