[Fotemustine, a new nitrosourea derivative. Current status of development].
Fotemustine is a new chloronitrosourea recently developed by the French company Servier. It is chemically characterized by the graft of an aminophosphonic acid on the chloronitrosourea radical, which makes it highly lipophil. The preclinical studies revealed a lower mutagenicity and hepatotoxicity when compared to BCNU. The pharmacokinetic studies showed a high body clearance and a short half-life. The phase I study enabled us to determine the definitive treatment schedule: 100 mg/m2/week during 3-4 consecutive weeks followed by 5 weeks' rest and a maintenance therapy of 100 mg/m2 every 3 weeks for stabilized or responding patients. Fotemustine should be given as a 1-h intravenous infusion, protected from daylight. There was no life-threatening toxicity and positive activity was observed in different tumors and especially melanomas. This indication was thus chosen for the phase II study. Among the 153 evaluable patients, the response rate reached 24.2%. It depended on the location of the metastatic sites, with 25% brain metastases, 19.2% visceral metastases, 8.8% liver metastases and 31.8% skin and lymph node metastases. The median duration of response was 22 weeks. The median overall survival of responding patients reached 85 weeks, while it dropped to 52 weeks in case of minor response or stabilization and 17 weeks in case of progression. The hematological toxicity was moderate (WHO grade III and IV: 46.3% leukopenia and 40.3% thrombopenia) and delayed as for other nitrosoureas (nadir: white blood cells: day 44 and thrombocytes: day 35).(ABSTRACT TRUNCATED AT 250 WORDS)
Institut de Recherches Internationales Servier, Neuilly s/Seine, France.
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D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004341:Drug Evaluation; D006801:Humans; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D009369:Neoplasms / Q000188:drug therapy*; D009607:Nitrosourea Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D009943:Organophosphorus Compounds / Q000008:administration & dosage* / Q000009:adverse effects
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; C054368:fotemustine
Fotemustin, ein neues Nitroso-Harnstoff-Derivat. Aktueller Stand der Entwicklung.