Oral Vinorelbine Promising and Well Tolerated in Patients With Advanced Breast Cancer

February 1, 1997

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

A group of French scientists concluded that oral vinorelbine (Navelbine)administered at a weekly dose of 80 mg/m² is well tolerated by patientswith advanced breast cancer. While intravenous vinorelbine has previouslyproven to be highly effective in the treatment of breast cancer, the advantagesof the new oral formulation of vinorelbine were outlined in a poster presentationby Dr. B. Chevallier et al of the Centre Henri Becquerel in Rouen, France,at the 19th Annual San Antonio Breast Cancer Symposium. The investigatorsnoted the particular value of oral therapy from the perspective of patientsand in terms of chronic or palliative treatment.

The intent of this phase I study was to determine the maximum tolerateddose of oral vinorelbine administered weekly, which was defined as thedose above which more than a 50% incidence of grade 4 hematologic or grades3 to 4 nonhematologic toxicity occur. Further, researchers sought to designatea recommended dose for future trials and to evaluate the drug's activityprofile.

Initial doses of 60 mg/m²/wk were increased by stepwise incrementsof 20 mg/m² in subsequent cohorts of six patients each. Upon obtainingthe maximum tolerated dose, six more patients were included at the previouslevel 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 vinorelbineat 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, and19 had been treated previously for advanced/metastatic disease. Predominantlyvisceral 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 thefirst six patients revealed three instances of grade 4 neutropenia, twocases 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 therewere 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 constipationoccurred after 1% of cycles. Anemia and thrombocytopenia were not observedabove grade 2 at any dose level, and only one patient experienced grade3 alopecia.

Efficacy results were promising, the investigators commented. Of themore than 13 evaluable patients treated at 80 mg/m²/wk, two received100 mg/m² for two courses and then 80 mg/m²/wk. Six partial responseswere observed, of which three were in patients with visceral disease. Themean duration of response was 30 weeks.