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

BANGOR, United Kingdom-The possibility exists of developing anall-oral regimen for advanced breast cancerthat is both effective and well tolerated.In progressing toward that objective,investigators conducting a phase II study(ASCO abstract 183) report that a combinationof intravenous vinorelbine (Navelbine)and oral capecitabine (Xeloda)demonstrated good activity in advancedbreast cancer patients who had been previouslytreated with anthracycline or anthracenedione."The possibility of developing an alloralregimen is attractive," noted NicholasStuart, MD, School of Biological Sciences,University of Bangor, UnitedKingdom. "The ideal chemotherapy regimenfor metastatic breast cancer is effective,well tolerated and convenient. Newagents need to be evaluated with thisideal in mind. Oral chemotherapy is anattractive option for many patients, especiallydue to its convenience."Dr. Stuart reported at last year's AmericanSociety of Clinical Oncology meetingthat the combination of vinorelbineand fluorouracil given by continuous infusionis active and well tolerated. "Weaimed to develop a regimen that would betolerable and equally effective after ananthracycline and/or a taxane, and wouldavoid the problems of continuous infusion,"Dr. Stuart said."This current study is the next steptowards creating such a chemotherapyregimen. In particular, the regimen appearseffective even in women who havealready received the two most active drugsin breast cancer-doxorubicin and a taxane,such as paclitaxel. To this end, weevaluated the tolerability and effectiveness of the combination of capecitabineand vinorelbine."Study Design andEligibility CriteriaThe regimen in the study consisted ofcapecitabine 1,000 mg/m² twice daily for14 days each 21-day cycle, and vinorelbine25 mg/m² IV (max 60 mg) days 1 and8 each 21 day cycle. Treatment continueduntil disease progression, unacceptabletoxicity, patient request, or to a maximumof eight cycles.To be eligible for the study, patientswere required to have histologically orcytologically confirmed female breast cancer;progressive, locally advanced, or metastaticdisease; previous chemotherapywith anthracycline or anthracenedione;one or two previous chemotherapy regimens;an Eastern Cooperative OncologyGroup (ECOG) Performance Status of 0to 2; and normal full blood count, liverfunction, and renal function. Excludedwere patients with previous irradiationtherapy to measurable disease sites, previous treatment with vinorelbine orcapecitabine, uncontrolled hypercalcemiaor central nervous system metastases, orclinically significant cardiac disease.Eighty-five patients were enrolled inthe study and data are available on 58patients. The median age is 56 years (range27-80). Of these 58 patients, 46 had priortreatment with anthracycline, and 35 hadprior treatment with adjuvant anthracycline.Thirteen patients had prior taxanetreatment.Median Achieved DosesThe median achieved dose of vinorelbinewas 42 mg/m²/3 weeks, which was84% of the intended dose. The mediandose of capecitabine over 3 weeks was1,051 mg/m², 79% of the intended dose.Fifty-three percent of treatments weredelayed, 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%). Therewere no treatment-related deaths.The overall response rate (n = 40) was43%, with 3% complete response and40% partial response. In addition, 15%had stable disease, 35% progressive disease,and 8% were not assessed because ofearly cessation of treatment due to patientrequest or death."Vinorelbine and capecitabine in combinationis an active regimen, and theactivity is comparable to that reportedwith vinorelbine and fluorouracil (43%and 50% response rates, respectively),"Dr. Stuart summarized. "The regimen isactive after prior treatment with anthracyclines.Vinorelbine and capecitabinecombination therapy is generally well tolerated,with neutropenia from vinorelbine being common but rarely severe."The Next StudyDr. Stuart's next phase II study willassess the oral formulation of vinorelbinein combination with capecitabine. Theprospect of oral vinorelbine raises thepossibility of a highly active all-oral regimenfor metastatic breast cancer. "Theaim is to devise a regimen that can begiven all orally and still be just as effective,"Dr. Stuart said. "The recent introductionof oral vinorelbine allows thispossibility to be tested. A similar studycombining oral vinorelbine with oralcapecitabine is due to start later this year.The possibility exists that an effective,well tolerated, and convenient oral regimenfor advanced breast cancer can bedeveloped."