A group of French scientists concluded that oral vinorelbine (Navelbine) administered at a weekly dose of 80 mg/m² is well tolerated by patients with advanced breast cancer. While intravenous vinorelbine has previously proven to be highly effective in the treatment of breast cancer, the advantages of the new oral formulation of vinorelbine were outlined in a poster presentation by Dr. B. Chevallier et al of the Centre Henri Becquerel in Rouen, France, at the 19th Annual San Antonio Breast Cancer Symposium. The investigators noted the particular value of oral therapy from the perspective of patients and in terms of chronic or palliative treatment.
The intent of this phase I study was to determine the maximum tolerated dose of oral vinorelbine administered weekly, which was defined as the dose above which more than a 50% incidence of grade 4 hematologic or grades 3 to 4 nonhematologic toxicity occur. Further, researchers sought to designate a recommended dose for future trials and to evaluate the drug's activity profile.
Initial doses of 60 mg/m²/wk were increased by stepwise increments of 20 mg/m² in subsequent cohorts of six patients each. Upon obtaining the maximum tolerated dose, six more patients were included at the previous level in order to confirm the recommended dose.
Interim results of this ongoing study were available for 27 patients, whose ages ranged from 37 to 77 years. Seven were treated with vinorelbine at 60 mg/m², 14 patients at 80 mg/m², and 6 patients at 100 mg/m². Six patients had been treated previously with adjuvant chemotherapy, and 19 had been treated previously for advanced/metastatic disease. Predominantly visceral disease was present in 50% of patients; nine had bone metastases; and locally advanced/metastatic disease was detected in 16 patients.
The maximum tolerated dose was 100 mg/m²/wk. Observation of the first six patients revealed three instances of grade 4 neutropenia, two cases of grades 3 to 4 constipation, and two episodes of grade 3 vomiting. Consequently, 80 mg/m²/wk was defined as the recommended dose.
Grades 3- to 4 neutropenia occurred following 21.4% of cycles, but there were no clinical consequences. There were no instances of grade 3 nausea; grades 3 to 4 vomiting followed 1.4% of cycles; and grades 3 to 4 constipation occurred after 1% of cycles. Anemia and thrombocytopenia were not observed above grade 2 at any dose level, and only one patient experienced grade 3 alopecia.
Efficacy results were promising, the investigators commented. Of the more than 13 evaluable patients treated at 80 mg/m²/wk, two received 100 mg/m² for two courses and then 80 mg/m²/wk. Six partial responses were observed, of which three were in patients with visceral disease. The mean duration of response was 30 weeks.