Effects of the modulating agent WR2721 on myelotoxicity and antitumour activity in carboplatin-treated mice

Carboplatin combined with amifostine, a bone marrow protectant, in the treatment of non-small-cell lung cancer: A randomised phase II study

“…In mice with ovarian carcinoma xenografts (Treskes et al, 1994) amifostine administered before carboplatin had a potentiating effect on tumour growth inhibition. In a randomised trial in patients with ovarian cancer (Glick et al, 1992) complete responses and survival with a median follow-up of 40 months were similar.…”

“…In animal models, it also protects normal tissue against the toxicity of cytotoxic agents such as platinum and alkylating compounds (Yuhas et al, 1980;Patchen et al, 1992;Treskes et al, 1994;van der Vijgh et al, 1994). Amifostine is a prodrug that is dephosphorylated to its active metabolite, a free thiol, by alkaline phosphatase at the tissue site.…”

Influence of single and multiple doses of amifostine on the efficacy and the pharmacokinetics of carboplatin in mice

“…Efficient protection against cisplatin-induced nephrotoxicity was observed in mice when amifostine was administered 5 min or 30 min before cisplatin (Treskes et al, 1992a). Protection against carboplatin-induced myelotoxicity was more obvious when amifostine was given 5 min instead of 30 min before carboplatin (Treskes et al, 1994). With respect to the long elimination half-life of non-protein-bound carboplatin in comparison with amifostine (van der Vijgh, 1991), greater myeloprotection might be achieved by multiple doses of amifostine when combined with carboplatin.…”

“…The clinical use of carboplatin is limited by myelosuppression at a dose in the steep part of the dose-response curve. Therefore, much effort has been put into reducing the toxic side-effects to allow the administration of higher doses of carboplatin.Amifostine [Ethyol, WR-2721, S-2-(3-aminopropylamino)-ethylphosphorothioic acid], initially developed as a radioprotector, is approved for use as a protector against chemotherapy-induced toxicities in the USA and Europe (van der Vijgh and Peters, 1994). A selective protection against the side-effects of platinum compounds has been observed in clinical and preclinical studies (Treskes et al, 1992a(Treskes et al, , 1994 Capizzi, 1994;van der Vijgh and Peters, 1994).…”

“…Amifostine [Ethyol, WR-2721, S-2-(3-aminopropylamino)-ethylphosphorothioic acid], initially developed as a radioprotector, is approved for use as a protector against chemotherapy-induced toxicities in the USA and Europe (van der Vijgh and Peters, 1994). A selective protection against the side-effects of platinum compounds has been observed in clinical and preclinical studies (Treskes et al, 1992a(Treskes et al, , 1994Capizzi, 1994;van der Vijgh and Peters, 1994).…”