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.
Six of 13 evaluable patients had partial responses to vinorelbine doses of 80 to 100 mg/m²/wk. Four of the responses occurred in patients previously treated with anthracycline-containing regimens. Three patients with visceral metastases had major responses. The oral therapy was 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-generation capsule we used in this study provides a more stable formulation," said Dr. Frederic Le Bras, associate director of medical affairs at the Pierre Fabre Research Institute.
The primary purpose of the study, which involved 27 patients with advanced breast cancer, was to determine the maximum tolerated dose (MTD) of the oral formulation. MTD was defined as more than 50% incidence of grade 4 hematologic toxicity or grade 3/4 nonhematologic toxicity.
A Heavily Pretreated Population
Dosing began at 60 mg/m²/wk (six patients) and was escalated by 20 mg/m²/wk in subsequent groups of six patients. Treatment continued until the cancer progressed or unacceptable toxicity occurred. The MTD proved to be 100 mg/m²/wk, and the results suggested a recommended dose of 80 mg/m²/wk for future trials.
The study patients represented a heavily pretreated population; 23 of 27 had received prior chemotherapy, and similar numbers had undergone hormonal therapy and radiation therapy, in addition to surgery. Nine patients had received two or more chemotherapy regimens.
The majority of patients had metastases at enrollment, 16 with soft tissue 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/wk and two patients initially treated at 100 mg/m² and then maintained on 80 mg/m²/wk. Median response duration was 30 weeks; one patient had a response that persisted beyond 60 weeks.
Four of the six responses occurred in soft tissue lesions, and three patients had responses involving more than one site. Overall, the sites of response included bone, lung, liver, and soft tissue.
Four responders had previously received anthracycline therapy, and three had 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 developed grade 3/4 neutropenia during 21% of cycles. None developed grade 3/4 thrombocytopenia or anemia.
"The 40% to 50% response rate seen in this preliminary trial is very encouraging, because many of these patients had been pretreated with other chemotherapies," Dr. Le Bras said. "Based on these results, I think we can say that 60 to 80 mg/m²/wk of oral vinorelbine probably will be equivalent to 25 to 30 mg/m² of the IV agent."
The researchers also think that oral vinorelbine likely has antitumor activity equivalent to that of the IV formulation. They are now evaluating the oral drug's activity in a phase II study, and eventually plan to evaluate the oral and IV formulations in a phase II randomized trial in stage IIIB/IV non-small cell lung cancer patients.
