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

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State: Public
Version: Final published version
Serval ID
serval:BIB_10BD30798F7E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Treatment of advanced soft-tissue sarcomas using a combined strategy of high-dose ifosfamide, high-dose doxorubicin and salvage therapies.
Journal
British journal of cancer
Author(s)
Leyvraz S., Herrmann R., Guillou L., Honegger H.P., Christinat A., Fey M.F., Sessa C., Wernli M., Cerny T., Dietrich D., Pestalozzi B.
Working group(s)
Swiss Group for Clinical Cancer Research (SAKK)
ISSN
0007-0920 (Print)
ISSN-L
0007-0920
Publication state
Published
Issued date
20/11/2006
Peer-reviewed
Oui
Volume
95
Number
10
Pages
1342-1347
Language
english
Notes
Publication types: Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.

Keywords
Adolescent, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Dose-Response Relationship, Drug, Doxorubicin/administration & dosage, Female, Humans, Ifosfamide/administration & dosage, Male, Middle Aged, Neoplasm Recurrence, Local/drug therapy, Neoplasm Recurrence, Local/pathology, Prognosis, Salvage Therapy, Sarcoma/drug therapy, Sarcoma/pathology, Soft Tissue Neoplasms/drug therapy, Soft Tissue Neoplasms/pathology, Survival Rate, Treatment Outcome
Pubmed
Web of science
Open Access
Yes
Create date
25/04/2008 12:35
Last modification date
20/08/2019 13:37
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