Annals of Oncology Advance Access originally published online on February 24, 2006
Annals of Oncology 2006 17(4):646-651; doi:10.1093/annonc/mdl020
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© 2006 European Society for Medical Oncology
Long-term results of a multicenter SAKK trial on high-dose ifosfamide and doxorubicin in advanced or metastatic gynecologic sarcomas
1 Centre Pluridisciplinaire d'Oncologie, University Hospital, Lausanne; 2 Pathology Institute, Kantonsspital, Basel, Switzerland; 3 Clinica Ostetrica e Ginecologica, Universita degli Studi Milano-Bicocca, Ospedale S. Gerardo dei Tintori, Monza, Italy; 4 Oncology/Hematology, Kantonsspital, St. Gallen; 5 Istituto Oncologico della Svizzera italiana, Bellinzona; 6 Institute of Medical Oncology, Inselspital, Bern; 7 Coordinating Center SAKK, Bern; 8 City Hospital Triemli, Zurich, Switzerland
* Correspondence to: Dr S. Leyvraz, Centre Pluridisciplinaire d'Oncologie, University Hospital – CHUV BH06, Rue du Bugnon 46, 1011 Lausanne, Switzerland. Tel: +41-21-313-01-50; Fax: +41-21-314-01-81; E-mail: Serge.Leyvraz{at}hospvd.ch
Background: Dose intensive chemotherapy has not been tested prospectively for the treatment of gynecologic sarcomas. We investigated the antitumor activity and toxicity of high-dose ifosfamide and doxorubicin, in the context of a multidisciplinary strategy for the treatment of advanced and metastatic, not pretreated, gynecologic sarcomas.
Patients and methods: Thirty-nine patients were enrolled onto a phase I–II multicenter trial of ifosfamide, 10 g/m2 as a continuous infusion over 5 days, plus doxorubicin intravenously, 25 mg/m2/day for 3 days with Mesna and granulocyte-colony-stimulating factor every 21 days. Salvage therapy was allowed after chemotherapy.
Results: Among the 37 evaluable patients, the tumor was locally advanced (n = 11), with concomitant distant metastases (n = 5) or with distant metastases only (n = 21). After a median of three (range 1–7) chemotherapy cycles, six patients experienced a complete response and 12 a partial response for an overall response rate of 49% (95% CI 32% to 66%). The response rate was higher in poorly differentiated tumors (62%) compared with moderately well differentiated ones (18%), but was not different according to histology subtypes. Eleven patients had salvage therapy, either immediately following chemotherapy (n = 7) or at time of progression (n = 4). With a median follow-up time of 5 years, the median overall survival was 30.5 months. Hematological toxicity was as expected neutropenia, thrombopenia and anemia 
grade 3 at 50%, 34% and 33% of cycles respectively. No toxic death occurred.
Conclusions: High-dose ifosfamide plus doxorubicin is an active regimen for all subtypes of gynecological sarcomas. Its toxicity was manageable in a multicentric setting. The prolonged survival might be due to the multidisciplinary strategy that was possible in one-third of the patients.
Key words: gynecologic sarcomas, leiomyosarcomas, endometrial stromal sarcomas, mixed mesodermal tumors, ifosfamide, doxorubicin