Vinorelbine/Capecitabine Can Be Used in Patients Pretreated With Anthracyclines or Taxanes

ESSEN, Germany—The combination of capecitabine (Xeloda) plus vinorelbine (Navelbine) is feasible and has a favorable toxicity profile in anthracycline-pretreated or taxane-pretreated advanced breast cancer, according to results of a recent phase I/II study. "The response rate over 50% is very promising," noted Udo Vanhoefer, MD, professor of medicine at University of Essen Medical School in Germany. "We had no alopecia, the incidence of hand-foot syndrome is very low, and the dose density is very high at 90% and very acceptable for this combination."

The median age of the 33 patients in this study was 54 years (range 30 to 69). The most common sites of metastases were liver, in 21 patients (64%), and bone, in 17 patients (51%). All but one patient received prior anthracyclines, and 12 (36%) had prior taxane exposure.

All patients received the combination of vinorelbine, which has significant activity in advanced breast cancer, and capecitabine, which is a tumor-activated oral fluoropyrimidine. Previously, researchers had shown vinorelbine plus infusional 5-FU to be active in metastatic breast cancer.

Vinorelbine Dose Reduced

Overall response rate among the 29 evaluable patients was approximately 51%, including a 10% complete response rate (3 patients) and a 41% partial response rate (12 patients). Another 14% (4 patients) had stable disease. Median time to progression was 32 weeks.

The main toxicity was neutropenia, and other toxicities were mild. Investigators reported only one case of grade 2 hand-foot syndrome.

Median relative dose density was 0.9 for both capecitabine and vinorelbine. The dosing schedule was vinorelbine IV on days 1, 8, 22, and 29, with capecitabine orally twice daily for two 2-week periods, starting on days 1 and 22 of the 42-day (6 week) cycle.

Investigators tried three dosing levels. The maximum tolerated dose was found to be vinorelbine 30 mg/m²/day and capecitabine 1,000 mg/m² twice daily, with neutropenia and diarrhea being the dose-limiting toxicities. Subsequently, the last 18 patients enrolled in this investigation all received treatment at vinorelbine 25 mg/m² and capecitabine 1,000 mg/m² twice daily, which became the recommended dose.

Combination Supported

These findings further support the combined use of vinorelbine and fluoropyrimidine therapy in advanced breast cancer. At the American Society of Clinical Oncology 2000 conference, Dr. Vanhoefer and colleagues had reported that the combination of vinorelbine, folinic acid, and 5-FU infusion was well tolerated and had promising antitumor efficacy in metastatic breast cancer patients with prior exposure to anthracycline-containing or taxane-containing chemotherapy (Borquez D , et al: Proc Am Soc Clin Oncol 19: Abstract 420, 2000).

Of 45 evaluable patients in that study, the overall response rate was 47% (21 patients), and an additional 36% (16 patients) had stable disease. Grade 3/4 leukopenia was observed in 35 of 88 cycles (40%), only four of which were grade 4 (5%). Other toxicities, such as alopecia and diarrhea, were mild and mostly grade 1 or 2.

Further studies are planned. Investigators believe vinorelbine plus capecitabine represents a promising potential regimen for advanced breast cancer, Dr. Vanhoefer said "especially if you compare that to the combination of capecitabine plus taxanes. I think the toxicity profile is very much in favor of the vinorelbine combination."