Prospective Randomized Trial of Docetaxel Versus Doxorubicin in Patients With Metastatic Breast Cancer By Stephen Chan, Kay Friedrichs, Daniel Noel, Tama ` s Pinte ´r, Simon Van Belle, Daniel Vorobiof, Ricardo Duarte, Miguel Gil Gil, Istvan Bodrogi, Elizabeth Murray, Louise Yelle, Gunter von Minckwitz, Stefan Korec, Peter Simmonds, Franco Buzzi, Rosario Gonza ´lez Mancha, Gary Richardson, Euan Walpole, Monica Ronzoni, Michael Murawsky, May Alakl, Alessandro Riva, and John Crown for the 303 Study Group Purpose: This phase III study compared docetaxel and doxorubicin in patients w ith metastatic breast can- cer w ho had received previousalkylating agent–contain- ing chemotherapy. Patients and Methods: Patients w ere randomized to receive an intravenousinfusion of docetaxel 100 mg/ m 2 or doxorubicin 75 mg/ m 2 every 3 weeks for a maxi- mum of seven treatment cycles. Results: A total of 326 patients were randomized, 165 to receive doxorubicin and 161 to receive doce- taxel. Overall, docetaxel produced a significantly higher rate of objective response than did doxorubicin (47.8% v 33.3%; P  .008). Docetaxel was also significantly more active than doxorubicin in patients w ith negative prognostic factors, such as visceral metastases (objec- tive response, 46% v 29%) and resistance to prior chemotherapy (47% v 25%). Median time to progres- sion w as longer in the docetaxel group (26 w eeks v 21 weeks; difference not significant). Median overall sur- vival was similar in the two groups (docetaxel, 15 months; doxorubicin, 14 months). There w as one death due to infection in each group, and an additional four deaths due to cardiotoxicity in the doxorubicin group. Although neutropenia was similar in both groups, fe- brile neutropenia and severe infection occurred more frequently in the doxorubicin group. For severe nonhe- matologic toxicity, the incidences of cardiac toxicity, nausea, vomiting, and stomatitis were higher among patients receiving doxorubicin, w hereas diarrhea, neu- ropathy, fluid retention, and skin and nail changesw ere higher among patientsreceiving docetaxel. Conclusion: The observed differences in activity and toxicity profiles provide a basis for therapy choice and confirms the rationale for combination studies in early breast cancer. J Clin Oncol 17:2341-2354.  1999 by American Society of Clinical Oncology. D ESPITE ADVANCES IN screening, locoregional treat- ment, and systemic adjuvant therapy for breast can- cer, metastatic relapse is still common. The recent meta- analysis of adjuvant breast cancer trials indicated that after adjuvant polychemotherapy, 40% of patients had a recur- rence, many of them, it can be assumed, with distant metastases. 1 For patients with advanced breast cancer whose tumors express the estrogen and/or progesterone receptor, endocrine therapy, as well as chemotherapy, can provide palliation, but for patients with receptor-negative cancers, those whose disease has become resistant to endocrine manipulations, and those in whom impending organ failure necessitates a rapid response, cytotoxic chemotherapy is generally the first treatment option to be considered. Since its introduction in the early 1970s, doxorubicin has generally been considered to be the most active chemothera- peutic agent in the treatment of metastatic breast cancer. In particular, in patients with advanced breast cancer who have received previous alkylating agent chemotherapy, doxorubi- cin monotherapy has produced response rates of 25% to 33% at doses ranging from 60 to 75 mg/m 2 , with median times to progression between 2.7 and 4.5 months. 2-7 Mono- therapy with epirubicin or mitoxantrone 4,7-10 has not im- proved further the results obtained with doxorubicin as a single agent in this patient population. From the Department of Clinical Oncology, City Hospital, Notting- ham, and CRC Wessex Medical Oncology Unit, Royal South Hants Hospital, Southampton, United Kingdom; Universita ¨ts-Frauenklinik und Poliklinik, Universita ¨ts-Krankenhaus Eppendorf, Hamburg, and Klinik fu ¨r Gyna ¨kologie und Onkologie, Klinikum der Johann Wolfgang Goethe-Universita ¨ t, Frankfurt, Germany; Oncology Department, Ho ˆpi- tal du Sacre ´-Coeur de Montreal, and Oncology Department, Ho ˆpital Notre-Dame, Montreal, Quebec, Canada; Oncoradiology Department, Country Hospital, Gyor, and National Institute of Oncology, Budapest, Hungary; Dienst Medische Oncologie, Universitair Ziekenhuis Gent, Gent, Belgium; The Sandton Oncology Centre, Johannesburg, and Department of Radiation Oncology, Groote Schuur Hospital, Cape Town, South Africa; National Institute of Cancerology, Bogota, Colom- bia; Servicio Oncologı ´a, Instituto Catala ´n de Oncologı ´a, Barcelona, and Servicio Oncologı ´a, Hospital Provincial, Cordova, Spain; National Cancer Institute, Bratislava, Slovakia; Servizio Oncologico, Ospedale Civile S. Maria, Terni, and Unita di Radiochemioterapia, Ospedale San Raffaele, Milan, Italy; Department of Medical Oncology and Clinical Haematology, Monash Medical Centre, Clayton, Victoria, and Depart- ment of Medical Oncology, Princess Alexandra Hospital, Woolloong- abba, Queensland, Australia; Rho ˆne-Poulenc Rorer, Antony, France; and St Vincent Hospital, Dublin, Ireland. Submitted August 24, 1998; accepted March 30, 1999. Sponsored by Rho ˆne-Poulenc Rorer, Antony, France. Address reprint requests to Stephen Chan, DM, MRCP, FRCR, Department of Clinical Oncology, City Hospital, Hucknall Rd, Notting- ham NG5 1PB, United Kingdom; email ytschan@innotts.co.uk.  1999 by American Society of Clinical Oncology. 0732-183X/99/1708-2341 Journal of Clinical Oncology, Vol 17, No 8 (August), 1999: pp 2341-2354 2341 Downloaded from ascopubs.org by University of Queensland on February 1, 2017 from 130.102.082.083 Copyright © 2017 American Society of Clinical Oncology. All rights reserved.