Treatment of advanced soft-tissue sarcomas using a combined strategy of high-dose ifosfamide, high-dose doxorubicin and salvage therapies.
Details
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State: Public
Version: Final published version
UNIL restricted access
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
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
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