In Vitro Cytotoxic Effect of Melphalan and Pilot Phase II Study in Hormone-refractory Prostate Cancer

• Published in: Anticancer research 2006-05, Vol.26 (3B), p.2197-2203
• Main Authors: MOUGENOT, Philippe, BRESSOLLE, Francoise, CULINE, Stéphane, SOLASSOL, Isabelle, POUJOL, Sylvain, PINGUET, Fréderic
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Androgens - physiology; Antineoplastic Agents, Alkylating - administration & dosage; Antineoplastic Agents, Alkylating - adverse effects; Antineoplastic Agents, Alkylating - pharmacokinetics; Biological and medical sciences; Cell Growth Processes - drug effects; Cell Line, Tumor; Drug Administration Schedule; Drug Screening Assays, Antitumor; Humans; Infusions, Intravenous; Male; Medical sciences; Melphalan - administration & dosage; Melphalan - adverse effects; Melphalan - pharmacokinetics; Middle Aged; Neoplasms, Hormone-Dependent - drug therapy; Neoplasms, Hormone-Dependent - metabolism; Neoplasms, Hormone-Dependent - pathology; Nephrology. Urinary tract diseases; Pilot Projects; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 0250-7005; 1791-7530

The objective of this study was to determine the impact of single versus sequential exposure to melphalan on the proliferation of an androgen-independent prostate cell line, PC-3, and to report the results of a pilot phase II study. For exposure to a single bolus dose, the doses were added at the start of the study and cell culture was continued for 96 h. For sequential exposure, 1/9 of the dose was added every 1.5 h over 12 h, followed by cell culture for 84 h. Cell growth inhibition was determined by the MTT assay. The clinical study was carried out on 14 patients with advanced prostate cancer. Melphalan was infused over a 24-h period. The sequential-dose schedule was more effective than the single-dose exposure, IC 50 values: 0.074 versus 0.77 μg/ml. Out of the 14 patients (42 courses) enrolled into the study, two patients were removed within the first 2 weeks because of rapid disease progression. The toxicity profile did not differ greatly from that reported after a 1-h infusion. Four PR and two SD were observed. The median survival of the twelve patients was 23 weeks. Melphalan administered over a 24-h period to patients with androgen-independent prostate cancer appeared to provide some clinical benefits with manageable toxicity.