Oral Vinorelbine Is Promising in Advanced Breast Cancer Patients

February 1, 1997

BOULOGNE, France-An oral formulation of vinorelbine (Navelbine) demonstrated encouraging antitumor activity and proved to be well tolerated in a phase I study of patients with advanced breast cancer, French physicians reported in a poster presentation.

BOULOGNE, France—An oral formulation of vinorelbine (Navelbine) demonstratedencouraging antitumor activity and proved to be well tolerated in a phaseI study of patients with advanced breast cancer, French physicians reportedin a poster presentation.

Six of 13 evaluable patients had partial responses to vinorelbine dosesof 80 to 100 mg/m²/wk. Four of the responses occurred inpatients previously treated with anthracycline-containing regimens. Threepatients with visceral metastases had major responses. The oral therapywas associated with a low rate of grade 3/4 toxicity.

"Some trials in the past used an oral formulation of vinorelbine,but the formulation was different than the current one. The third-generationcapsule we used in this study provides a more stable formulation,"said Dr. Frederic Le Bras, associate director of medical affairs at thePierre Fabre Research Institute.

The primary purpose of the study, which involved 27 patients with advancedbreast cancer, was to determine the maximum tolerated dose (MTD) of theoral formulation. MTD was defined as more than 50% incidence of grade 4hematologic toxicity or grade 3/4 nonhematologic toxicity.

A Heavily Pretreated Population

Dosing began at 60 mg/m²/wk (six patients) and was escalated by20 mg/m²/wk in subsequent groups of six patients. Treatment continueduntil the cancer progressed or unacceptable toxicity occurred. The MTDproved to be 100 mg/m²/wk, and the results suggested a recommendeddose of 80 mg/m²/wk for future trials.

The study patients represented a heavily pretreated population; 23 of27 had received prior chemotherapy, and similar numbers had undergone hormonaltherapy and radiation therapy, in addition to surgery. Nine patients hadreceived two or more chemotherapy regimens.

The majority of patients had metastases at enrollment, 16 with softtissue involvement, and 8 to 10 each with involvement of the lymph nodes,bone, lungs, or liver.

The six partial responses involved four patients treated at 80 mg/m²/wkand two patients initially treated at 100 mg/m² and then maintainedon 80 mg/m²/wk. Median response duration was 30 weeks; one patienthad a response that persisted beyond 60 weeks.

Four of the six responses occurred in soft tissue lesions, and threepatients had responses involving more than one site. Overall, the sitesof response included bone, lung, liver, and soft tissue.

Four responders had previously received anthracycline therapy, and threehad received two or more chemotherapy regimens at enrollment.

Seventeen patients were evaluable for toxicity over 295 cycles of therapy.Ten developed grade 3/4 leukopenia during 15% of cycles. Eleven developedgrade 3/4 neutropenia during 21% of cycles. None developed grade 3/4 thrombocytopeniaor anemia.

"The 40% to 50% response rate seen in this preliminary trial isvery encouraging, because many of these patients had been pretreated withother chemotherapies," Dr. Le Bras said. "Based on these results,I think we can say that 60 to 80 mg/m²/wk of oral vinorelbine probablywill be equivalent to 25 to 30 mg/m² of the IV agent."

The researchers also think that oral vinorelbine likely has antitumoractivity equivalent to that of the IV formulation. They are now evaluatingthe oral drug's activity in a phase II study, and eventually plan to evaluatethe oral and IV formulations in a phase II randomized trial in stage IIIB/IVnon-small cell lung cancer patients.