Treatment of advanced soft-tissue sarcomas using a combined strategy of high-dose ifosfamide, high-dose doxorubicin and salvage therapies

Leyvraz, S; Herrmann, R; Guillou, L; Honegger, HP; Christinat, A; Fey, MF; Sessa, C; Wernli, M; Cerny, T; Dietrich, D; Pestalozzi, B; Swiss, Group for Clinical Cancer Research (SAKK) (2006). Treatment of advanced soft-tissue sarcomas using a combined strategy of high-dose ifosfamide, high-dose doxorubicin and salvage therapies. British journal of cancer, 95(10), pp. 1342-7. Basingstoke: Nature Publishing Group 10.1038/sj.bjc.6603420

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Having determined in a phase I study the maximum tolerated dose of high-dose ifosfamide combined with high-dose doxorubicin, we now report the long-term results of a phase II trial in advanced soft-tissue sarcomas. Forty-six patients with locally advanced or metastatic soft-tissue sarcomas were included, with age <60 years and all except one in good performance status (0 or 1). The chemotherapy treatment consisted of ifosfamide 10 g m(-2) (continuous infusion for 5 days), doxorubicin 30 mg m(-2) day(-1) x 3 (total dose 90 mg m(-2)), mesna and granulocyte-colony stimulating factor. Cycles were repeated every 21 days. A median of 4 (1-6) cycles per patient was administered. Twenty-two patients responded to therapy, including three complete responders and 19 partial responders for an overall response rate of 48% (95% CI: 33-63%). The response rate was not different between localised and metastatic diseases or between histological types, but was higher in grade 3 tumours. Median overall survival was 19 months. Salvage therapies (surgery and/or radiotherapy) were performed in 43% of patients and found to be the most significant predictor for favourable survival (exploratory multivariate analysis). Haematological toxicity was severe, including grade > or =3 neutropenia in 59%, thrombopenia in 39% and anaemia in 27% of cycles. Three patients experienced grade 3 neurotoxicity and one patient died of septic shock. This high-dose regimen is toxic but nonetheless feasible in multicentre settings in non elderly patients with good performance status. A high response rate was obtained. Prolonged survival was mainly a function of salvage therapies.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
UniBE Contributor:	Fey, Martin
ISSN:	0007-0920
ISBN:	17031396
Publisher:	Nature Publishing Group
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:46
Last Modified:	05 Dec 2022 14:14
Publisher DOI:	10.1038/sj.bjc.6603420
PubMed ID:	17031396
Web of Science ID:	000242046700006
URI:	https://boris.unibe.ch/id/eprint/19003 (FactScience: 1368)