Phase II study of melphalan as a single-agent infused over a 24-hour period with individual adapted dosing in patients with recurrent epithelial ovarian cancer.
The current study was performed to evaluate the efficacy and toxicity of a chemotherapy treatment using melphalan administered over a 24-h period with individual adapted dosing in advanced ovarian cancer. Melphalan was infused intravenously with an automatic infusion pump over a 24-h period. The schedule was repeated every 28 days for a maximum of 6 cycles. The initial administered dose was 25 mg/m(2). Drug adjustment was then made using a population approach, with the aim of constraining the overall area under the plasma concentration-time curve within 2.0-2.5 mg . h/l. A total of 96 courses of chemotherapy was administered. The toxicity profile did not differ greatly from that reported after a 1-h infusion and was acceptable in such a heavily pretreated patient population. Twenty-five patients were assessable for response and survival. Four (16%) partial responses were observed, which lasted 9, 10, 13 and 37 months, respectively. Three patients experienced stable disease during 8, 14 and 22 months, respectively. The 1- and 2-year survival rates were 18% and 6%, respectively. At the time of analysis, two patients remained alive with progressive disease at 22 and 37 months, respectively. In conclusion, melphalan administered over a 24-h period in platinum- and taxane-resistant ovarian cancer patients appeared to provide some clinical benefits with manageable toxicity. Based on these results, future studies comparing melphalan administered over a 24-h period and oral melphalan administrations will be scheduled.
Mougenot
Philippe
P
Oncopharmacology Department, Pharmacy Service, Montpellier, France.
Fabbro
Michel
M
Bressolle
Françoise
F
Pouessel
Damien
D
Culine
Stephane
S
Pinguet
Frederic
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004848:Epithelium / Q000473:pathology; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan