Neoadjuvant Docetaxel Followed by Surgery, Doxorubicin/Cyclophosphamide, Radiation Is Active in Stage III Breast Ca

August 1, 2003

This special supplement to Oncology News International includes 28 reportswith updated information on clinical trials investigating capecitabine and other agents inthe treatment of advanced colorectal and breast cancers, and other solid tumors.The reports summarize selected presentations from the 39th Annual Meeting of theAmerican Society of Clinical Oncology (ASCO) and related educational symposiaheld in conjunction with ASCO.

BETHESDA, Maryland-Neoadjuvantdocetaxel (Taxotere) followedby surgery, adjuvant doxorubicin and cyclophosphamide(Cytoxan, Neosar), andradiation therapy is an active regimen forpatients with stage III breast cancer.Among 41 patients, clinical response ratesafter no more than four cycles of docetaxelwere 64% in the breast only and 58% inthe breast plus axilla.These results from a phase II studywere reported by Sandra Swain, MD, ofthe National Cancer Institute, Bethesda,MD (ASCO abstract 143).Describing the context for these results,Dr. Swain noted, "We previously reportedoutcomes in 33 women with stage III breastcancer treated with docetaxel 100 mg/m2q3wk x 4, followed by surgery, doxorubicin60 mg/m2 plus cyclophosphamide 600mg/m2 q3wk x 4, and radiation (Br Ca ResTreat 46:74, 1997). Patients with estrogenreceptor-positive tumors received tamoxifen.Here we describe updated responseand survival results from this phase IIstudy.""Emerging phase II data supporteddocetaxel's significant single-agent activityin patients with metastatic breast cancer,including previously untreated and anthracycline-refractory disease. Evaluating a cytotoxicagent in the neoadjuvant settingprovides an opportunity for assessing itspotential impact in locally advanced disease,as a prelude to further explorationwithin multiagent adjuvant chemotherapy.Thus, we designed a multicenter phaseII trial of neoadjuvant docetaxel, followedby surgery, adjuvant doxorubicin and cyclophosphamide,and then radiation therapyfor locally advanced breast cancer."Study DesignEligibility criteria include stage III adenocarcinomaof the breast; bidimensionallymeasurable lesion; no disease outsideof the breast, except for the ipsilateralaxillary nodes; Karnofsky performancestatus ≥ 60 and no prior chemotherapy,immunotherapy, or hormonal therapy forbreast cancer.Of the 45 patients enrolled in the study,patients completing each phase of treatmentper protocol were docetaxel (38 patients),surgery (31), doxorubicin and cyclophosphamide(23), and radiationtherapy (23).The primary end point of the studywas clinical response to docetaxel. Thesecondary end points were pathologiccomplete response to docetaxel, adverseevents and toxicity, median time to progression,and disease-free and overall survival(1-year and 2-year rates).Four of the 45 patients enrolled in thestudy were found to be ineligible. Amongthe 41 eligible patients, 36 in the breastplus axilla group were evaluable for clinicalresponse, and 29 were evaluable forpathologic response. In the breast onlycategory, 39 patients were evaluable forclinical response.Survival Rates and ResponsesOne-year overall survival was 95% (39of 41 patients) for all patients, 100% forstage IIIA patients, and 91% for stage IIIBpatients. In the breast only group, completeresponse was 18%, and partial responsewas 46%. Overall complete responsewas 8% in this group, and partialresponse was 43%.Pathologic findings for the 31 patientshaving surgery after doxorubicin x 4 weekswere pathologic complete response (breastplus axilla) of 10%, plus 6% with less than5 mm of residual invasive cancer. Medianfollow-up for the 41 eligible patients was5.6 years and 5-year disease-free survivalwas 80%.Neutropenia was the most commongrade 3/4 toxicity. The incidence of febrileneutropenia was 27% during docetaxeltherapy and 2% with doxorubicin andcyclophosphamide.Grade 3/4 nonhematologic toxicitiesthat occurred in ≥ 5% of patients includedasthenia and diarrhea.Results SummarizedIn summarizing the results of the study,Dr. Swain said, "Among the 41 patients,clinical response rates after no more thanfour cycles of docetaxel were 64% in breastonly and 58% in breast plus axilla. Basedon this finding, we conclude that neoadjuvantdocetaxel followed by surgery, adjuvantdoxorubicin and cyclophosphamide,and radiation is an active regimenfor patients with stage III breast cancer,with a pathologic complete response rateof 10% (breast plus axilla) and pN0 andpT0 rates of 38% and 14%, respectively."This is consistent with the data fromNational Surgical Adjuvant Breast andBowel Project (NSABP) B-27, in whichlower stage patients were treated. In thattrial, the pathologic complete responserate (breast only) was 13.7% for neoadjuvantdoxorubicin and cyclophosphamide,and increased to 25.6% with the additionof docetaxel after doxorubicin and cyclophosphamide-an absolute increase ofabout 12%. This finding suggests that docetaxelas a single agent makes a significantcontribution to response."In concluding, Dr. Swain observed,"The 5-year overall survival rate of 80%for patients with stage III breast cancer isvery encouraging, as are the 5-year overallsurvival rates for the subgroups of patientswith stage IIIA (84%) and IIIB (77%)disease. The findings indicate that neoadjuvantdocetaxel followed by surgery, adjuvantdoxorubicin, and cyclophosphamide,and radiation therapy is an activeregimen for patients with stage III breastcancer."