Short Course Intermediate Dose Intravenous Melphalan Therapy in Myeloma Relation to Early Emergence of Drug Resistance (Phase II Study)

Abstract

Intermediate dose intravenous melphalan at a dose of 15 mg/m² × 4 given at 21-day intervals has been evaluated in 20 consecutive patients. The aims were to assess the time to obtain maximal response, duration of response and response to reintroduction of intravenous melphalan on relapse. Median time to maximal response was 17 weeks. Four patients achieved a complete response with complete disappearance of parapro-tein. On relapse, reintroduction of intravenous melphalan was unsuccessful in causing a reduction of parapro-tein, suggesting that resistance to this dose of melphalan occurs early even in responding patients

Single-Dose Intravenous Melphalan in Advanced Multiple Myeloma

“…Intermediate intravenous doses of melphalan have been used ear lier. In one study [12], melphalan was used both as in itial therapy and at relapse. Ten out of 20 patients got a CR or PR of limited length and when given at re lapse no response was seen.…”

Intravenous injection of bortezomib, melphalan and dexamethasone in refractory and relapsed multiple myeloma

“…Several clinical pharmacokinetic studies have shown that melphalan has a short half-life in the plasma, and its absorption from the gastrointestinal tract is extremely variable [19][20][21]. In addition, if we consider the frequency of bortezomib-related gastrointestinal toxicity, it is reasonable to hypothesize that bortezomib could also hamper the melphalan absorption thus reducing its activity [22].…”