Phase II Study Makes Progress Toward an All-Oral Regimen for Advanced Breast Cancer

BANGOR, United Kingdom- The possibility exists of developing an all-oral regimen for advanced breast cancer that is both effective and well tolerated. In progressing toward that objective, investigators conducting a phase II study (ASCO abstract 183) report that a combination of intravenous vinorelbine (Navelbine) and oral capecitabine(Drug information on capecitabine) (Xeloda) demonstrated good activity in advanced breast cancer patients who had been previously treated with anthracycline or anthracenedione. "The possibility of developing an alloral regimen is attractive," noted Nicholas Stuart, MD, School of Biological Sciences, University of Bangor, United Kingdom. "The ideal chemotherapy regimen for metastatic breast cancer is effective, well tolerated and convenient. New agents need to be evaluated with this ideal in mind. Oral chemotherapy is an attractive option for many patients, especially due to its convenience." Dr. Stuart reported at last year's American Society of Clinical Oncology meeting that the combination of vinorelbine and fluorouracil(Drug information on fluorouracil) given by continuous infusion is active and well tolerated. "We aimed to develop a regimen that would be tolerable and equally effective after an anthracycline and/or a taxane, and would avoid the problems of continuous infusion," Dr. Stuart said. "This current study is the next step towards creating such a chemotherapy regimen. In particular, the regimen appears effective even in women who have already received the two most active drugs in breast cancer-doxorubicin and a taxane, such as paclitaxel(Drug information on paclitaxel). To this end, we evaluated the tolerability and effectiveness of the combination of capecitabine and vinorelbine." Study Design and Eligibility Criteria The regimen in the study consisted of capecitabine 1,000 mg/m² twice daily for 14 days each 21-day cycle, and vinorelbine 25 mg/m² IV (max 60 mg) days 1 and 8 each 21 day cycle. Treatment continued until disease progression, unacceptable toxicity, patient request, or to a maximum of eight cycles. To be eligible for the study, patients were required to have histologically or cytologically confirmed female breast cancer; progressive, locally advanced, or metastatic disease; previous chemotherapy with anthracycline or anthracenedione; one or two previous chemotherapy regimens; an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2; and normal full blood count, liver function, and renal function. Excluded were patients with previous irradiation therapy to measurable disease sites, pre vious treatment with vinorelbine or capecitabine, uncontrolled hypercalcemia or central nervous system metastases, or clinically significant cardiac disease. Eighty-five patients were enrolled in the study and data are available on 58 patients. The median age is 56 years (range 27-80). Of these 58 patients, 46 had prior treatment with anthracycline, and 35 had prior treatment with adjuvant anthracycline. Thirteen patients had prior taxane treatment. Median Achieved Doses The median achieved dose of vinorelbine was 42 mg/m²/3 weeks, which was 84% of the intended dose. The median dose of capecitabine over 3 weeks was 1,051 mg/m², 79% of the intended dose. Fifty-three percent of treatments were delayed, the primary cause being neutropenia. Grade 3/4 toxicities include nausea/ vomiting (6%), peripheral neuropathy (5%), diarrhea (2%), constipation (1%), and hand-foot syndrome (1%). There were no treatment-related deaths. The overall response rate (n = 40) was 43%, with 3% complete response and 40% partial response. In addition, 15% had stable disease, 35% progressive disease, and 8% were not assessed because of early cessation of treatment due to patient request or death. "Vinorelbine and capecitabine in combination is an active regimen, and the activity is comparable to that reported with vinorelbine and fluorouracil (43% and 50% response rates, respectively)," Dr. Stuart summarized. "The regimen is active after prior treatment with anthracyclines. Vinorelbine and capecitabine combination therapy is generally well tolerated, with neutropenia from vinorelbine being common but rarely severe." The Next Study Dr. Stuart's next phase II study will assess the oral formulation of vinorelbine in combination with capecitabine. The prospect of oral vinorelbine raises the possibility of a highly active all-oral regimen for metastatic breast cancer. "The aim is to devise a regimen that can be given all orally and still be just as effective," Dr. Stuart said. "The recent introduction of oral vinorelbine allows this possibility to be tested. A similar study combining oral vinorelbine with oral capecitabine is due to start later this year. The possibility exists that an effective, well tolerated, and convenient oral regimen for advanced breast cancer can be developed."