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Randomized Phase II Study of Docetaxel Versus Doxorubicin in First- and Second-Line Chemotherapy for Locally Advanced or Metastatic Soft Tissue Sarcomas in Adults: A Study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group

From the Department of Medical Oncology, Rotterdam Cancer Institute (Daniel den Hoed Kliniek) and University Hospital Rotterdam, and Department of Medical Oncology, University Hospital Radboud, Nijmegen, the Netherlands; Department of Medical Oncology, Christie Hospital, Manchester, Department of Oncology, Weston Park Hospital, Sheffield, and Department of Medical Oncology, Royal Marsden Hospital, Sutton, United Kingdom; Department of Surgery, Cancer Center M. Sklodowska Curie, Warsaw, Poland; Department of Medical Oncology, Hospital General de Asturias, Oviedo, Spain; European Organization for Research and Treatment of Cancer Data Center, Brussels, Belgium; and Rhône-Poulenc Rorer, Antony, France.

Address reprint requests to Jaap Verweij, MD, PhD, Department of Medical Oncology, Rotterdam Cancer Institute (Daniel den Hoed Kliniek) and University Hospital, Rotterdam, Groene Hilledijk 301, 3075 EA Rotterdam, the Netherlands; email verweij{at}onch.azr.nl

PURPOSE: To assess antitumor response and time to progression (TTP) with docetaxel compared with doxorubicin in first-line treatment of advanced and/or metastatic soft tissue sarcoma.

PATIENTS AND METHODS: Patients with measurable soft tissue sarcoma lesions and adequate bone marrow, liver, and renal function were entered onto the study. They were randomized to either docetaxel 100 mg/m² given as a 1-hour intravenous infusion every 3 weeks or doxorubicin 75 mg/m² given as a bolus injection every 3 weeks. A maximum of seven cycles of treatment were scheduled. The study was designed as a randomized phase III study evaluating TTP by log-rank model. There was a clause for premature closure of the trial if fewer than five responses were observed among the first 25 assessable patients in the docetaxel treatment arm.

RESULTS: Eighty-six patients were entered onto the study; 85 were assessable for toxicity and 83 for response. The rate of severe granulocytopenia was not significantly different between the two arms. Nausea (P = .001), vomiting (P < .001), and stomatitis (P = .005) were more common with doxorubicin therapy, whereas neurotoxicity was more frequent with docetaxel treatment. The response rate to doxorubicin therapy was 30% (95% confidence interval, 17% to 46%), whereas no responses to docetaxel therapy were seen (P < .001). In view of this, the trial was closed prematurely and the phase III study part was not conducted.

CONCLUSION: Docetaxel is inactive in soft tissue sarcomas and cannot be recommended for further use in treatment of this disease.

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