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

Abstract

Abstract. 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.

Dipeptidyl Peptidase IV as a Potential Target for Selective Prodrug Activation and Chemotherapeutic Action in Cancers

“…Melphalan, phenylalanine mustard (L-PAM), is an established anticancer agent that was originally approved for the treatment of multiple myeloma. Recently it has been suggested as a therapeutic agent in the treatment of a variety of cancers such as ovarian cancer, breast cancer, colorectal cancer, and melanoma . However, its use has been limited due to severe side effects such as bone marrow suppression, leukopenia, and thrombocytopenia, − largely due to lack of selectivity for cancer cells, and so it was selected as the model drug for investigating our approach.…”

Future Prospects for Old Chemotherapeutic Drugs in the Target-Specific Era; Pharmaceutics, Combinations, Co-Drugs and Prodrugs with Melphalan as an Example

“…Increasing the sodium chloride concentration to 3 % has improved stability to allow a 24 h infusion in a phase I trial [26]. Subsequent population pharmacokinetic analysis [27] and a phase II study with individual adapted dosing of single-agent melphalan in 25 patients with recurrent (platinum and taxane-resistant) epithelial ovarian cancer, resulted in four (16 %) partial responses and three (12 %) patients with stable disease [28]. Besides from this rather simple formulation there are remarkably few other suggestions to pharmaceutical preparations of melphalan with chemical, physiochemical or pharmacodynamic/kinetic properties different from those of Alkeran ® .…”