Vinorelbine/Capecitabine Represents Promising Alternative for Metastatic Breast Cancer

BEIRUT, Lebanon—Vinorelbine (Navelbine) plus capecitabine (Xeloda) is a highly effective and well tolerated first-line chemotherapy regimen for metastatic breast cancer, according to results of a recent 30-patient multicenter phase II trial. Investigators reported a response rate of 67%, with the main toxicity being grade 3/4 neutropenia in 13% of patients.

The combination represents a promising alternative regimen, with acceptable toxicity and improved patient convenience, according to investigator Marwan Ghosn, MD, associate professor and chairman of the department of hematology-oncology at Saint-Joseph University School of Medicine, Beirut, Lebanon.

"The toxicity is very mild, and can be managed very easily," Dr. Ghosn said. When oral vinorelbine becomes available he anticipated patients with metastatic breast cancer being able to receive all their first-line chemotherapy orally at home, rather than having to travel to a medical facility for IV treatment.

Dr. Ghosn reviewed previous research showing that the combination regimen of vinorelbine and fluorouracil (5-FU) is effective in advanced breast cancer and a subsequent phase I study, presented at San Antonio Breast Cancer Symposium in 2000, showing that capecitabine plus vinorelbine has promising antitumor activity. "Capecitabine should be able to replace the less convenient infusional 5-FU within combination chemotherapy regimens," Dr. Ghosn said.

Thirty Women Enrolled

Thirty women (median age 54 years) with metastatic breast cancer enrolled in the study of vinorelbine/capecitabine as first-line treatment. Nearly 75% of the patients had visceral metastasis, and nearly 75% had two or more metastatic sites. Prior treatment included adjuvant/neoadjuvant chemotherapy in 67% and hormone therapy in 57%. Prior treatment with capecitabine or vinorelbine was not allowed.

The 3-week schedule included vinorelbine 25 mg/m² IV on days 1 and 8, plus oral capecitabine 825 mg/m² twice daily for 14 days. Evaluation of antitumor activity occurred every 9 weeks, while safety was evaluated every cycle. Patients received a total of 195 cycles, with a median of six cycles per patient.

Response was recorded for 20 of 30 patients (67%), including two complete and 18 partial responses; an additional six patients had stable disease. Dr. Ghosn said that activity occurred regardless of metastatic site, with overall response rates ranging from 58% for liver metastases (7 of 12 patients) to 69% for lung metastases (9 of 13 patients).

Most Toxicities Mild

Grade 3/4 neutropenia occurred in 13% of patients, two with grade 3 and two with grade 4. Only one patient developed febrile neutropenia. Other toxicities were mild, and included grade 2 hand-foot syndrome in one patient, and grade 2 asthenia in 17% of patients. One patient experienced grade 3 vomiting and another experienced grade 3 mucositis.

"We were able to have a low rate of grade 3/4 toxicities because of a very strict dose tapering of the capecitabine dose immediately after appearances of any signs of toxicities, such as hand-foot syndrome or leukopenia at day 8 of the cycle," Dr. Ghosn added.

"These data, and the encouraging results with oral vinorelbine in other trials, should deserve the development of a full oral regimen as first-line chemotherapy in metastatic breast cancer," Dr. Ghosn said.

To further increase response, the investigators plan to test sequential capecitabine/vinorelbine and docetaxel (Taxotere) in a similar patient population. The planned regimen is capecitabine/vinorelbine for four cycles, followed by three or four cycles of docetaxel.