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[Amifostine: current and future applications in cytoprotection]
1Centre hospitalier intercommunal de Montfermeil, France.
Abstract:
Originally developed against the effects of ionizing radiations, amifostine is an organic thiophosphate compound shown able to selectively protect normal tissues against cytotoxic agents in cellular and animal models, without protecting tumor tissues. Amifostine is a prodrug which is dephosphorylated into its active metabolite, a free thiol derivative, by membrane alkaline phosphatase of the target issue. This unique metabolism supports its cellular selectivity and its preferential uptake by normal tissues. In phase II clinical trials, a decreased toxicity has been demonstrated in patients given alkylating agents; however, reduction of the response has not been observed. On the basis of these results, a prospective, randomized, phase III study has been conducted in patients with ovarian carcinoma receiving a combination of cisplatinum and cyclophosphamide. A significant decrease in hematologic, renal and neurologic toxicity was observed in the amifostine-treated patients compared with the control group, and response rates did not significantly differ between the two groups. Insufficient or emerging data are only available for other applications, including either in vitro manipulation of hematopoietic grafts or in vivo treatment of non-Hodgkin's lymphoma, head and neck carcinoma, non-small cell lung cancer and radioprotection. No data are yet available in regard to the potential protective effects of amifostine against mutagenicity and cancerogenicity of both chemo- and radiotherapy.
Insights
Amifostine selectively protects normal tissues from chemotherapy toxicity without reducing treatment effectiveness. This radioprotective drug offers a promising approach to mitigate side effects in cancer patients.
Area of Science:
- Oncology
- Pharmacology
Background:
- Amifostine, an organic thiophosphate, was developed to protect against ionizing radiation.
- It functions as a prodrug, metabolized to an active thiol by alkaline phosphatase, enabling selective normal tissue protection.
Purpose of the Study:
- To evaluate amifostine's efficacy in reducing chemotherapy-induced toxicity in ovarian cancer patients.
- To assess if amifostine impacts treatment response rates in combination chemotherapy.
Main Methods:
- A prospective, randomized phase III clinical trial.
- Patients with ovarian carcinoma received cisplatinum and cyclophosphamide, with or without amifostine.
Main Results:
- Amifostine significantly reduced hematologic, renal, and neurologic toxicities.
- No significant difference in response rates was observed between amifostine-treated and control groups.
Conclusions:
- Amifostine demonstrates significant radioprotective effects against chemotherapy toxicity in ovarian cancer.
- It improves patient tolerance to treatment without compromising anti-cancer efficacy.