The fate of new fosfamides in phase III studies in advanced soft tissue sarcoma.
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Date
2017-10Author
Constantinidou, A
van der Graaf, WTA
Type
Journal Article
Metadata
Show full item recordAbstract
For decades, doxorubicin alone or in combination with ifosfamide has been used in advanced soft tissue sarcoma (STS). In 2014, a comparison of doxorubicin alone versus the combination with ifosfamide (in the randomised phase III EORTC 62012) showed no difference in overall survival (OS), but a difference in response and progression-free survival (PFS) were observed in favour of the combination but at the expense of increased toxicity. Newer fosfamides, with slightly different modes of action, and potentially less toxicity, namely evofosfamide and palifosfamide have recently been tested in randomised phase III clinical trials in STS. The TH CR-406/SARC021 (June 2017) and the PICASSO III (September 2016) studies compared doxorubicin, as the standard arm, to doxorubicin in combination with evofosfamide and palifosfamide, respectively. In both studies, the combination arm produced increased response rates but at the expense of higher toxicity. However, there was no difference in OS or PFS in favour of the combination. Importantly, the median OS of patients receiving standard of care, doxorubicin, in both studies appeared improved from 12.8 months (95.5% CI 10.5-14·III) in the EORTC 62012 to 16.9 months (95% CI 14.8 to 22.9) in PICASSO III and 19.0 months (95% CI 16.2-22.4) in TH CR-406/SARC021. The results of these three randomised phase III studies highlight several critical issues related to the design and conduct of such trials in STS. We discuss these issues aiming to contribute to the ongoing debate about the optimal approach to perform clinical research in STS.
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Subject
Humans
Sarcoma
Soft Tissue Neoplasms
Phosphoramide Mustards
Nitroimidazoles
Antineoplastic Agents, Alkylating
Neoplasm Staging
Treatment Outcome
Risk Factors
Survival Analysis
Evidence-Based Medicine
Research Design
Time Factors
Randomized Controlled Trials as Topic
Clinical Trials, Phase III as Topic
Research team
Clinical and Translational Sarcoma
Language
eng
Date accepted
2017-07-25
License start date
2017-10
Citation
European journal of cancer (Oxford, England : 1990), 2017, 84 pp. 257 - 261