Fotemustine: an overview of its clinical activity in disseminated malignant melanoma.
Fotemustine is a new chloronitrosourea which is active against disseminated malignant melanoma (DMM), and especially against cerebral metastases (CM). This efficacy has been widely demonstrated through many phase II studies. A multicentre trial of monotherapy was undertaken in 153 evaluable French patients. A response rate (RR) of 24.2% (25.0% RR in CM; 31.8% in non-visceral metastases (NVM) was obtained. Three other phase II studies confirmed these results with respective objective RR of 16.7%, 20.0% and 47.0% and RR in CM of 8.3%, 14.3% and 60.0%. Fotemustine has also been used in combination with dacarbazine (DTIC), in patients with DMM. The RR among 103 patients was 27.2% (26.3% in CM, 37.5% in NVM), confirming the activity of fotemustine. The two drugs have also been administered sequentially, in order to exploit their synergism in interfering with the O6 alkyltransferase. Impressive RR have been achieved, especially in patients with visceral metastases (VM) but at the expense of a pulmonary toxicity that does not arise with other treatment schedules and which precludes its use outside of strictly conducted clinical trials.
Khayat
D
D
Hôpital Pitié Salpétrière, Service d'Oncologie Médicale, Paris, France.
Avril
M F
MF
Gerard
B
B
Bertrand
P
P
Bizzari
J P
JP
Cour
V
V
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000556:secondary / Q000628:therapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary / Q000628:therapy; D008545:Melanoma / Q000188:drug therapy / Q000556:secondary* / Q000628:therapy; D009607:Nitrosourea Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012074:Remission Induction; D014751:Vindesine / Q000008:administration & dosage
D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D011994:Recombinant Proteins; D003606:Dacarbazine; C054368:fotemustine; D014751:Vindesine