Melphalan And Other Alkylating Agents

Melphalan, usually in combination with prednisone (the "MP" regimen, Table 83.1), has been used to treat MM since the 1960s. A small randomized study comparing different schedules of melphalan, with or without prednisone, showed a distinct advantage in favor of intermittent ("pulse") melphalan with prednisone as compared to either pulse or daily melphalan alone,16 though not all subsequent studies have con firmed superiority of this schedule.17' 18 In the MP regimen, the initial dose of oral melphalan is 8-9 mg/m2 daily along with prednisone 100 mg/day (or 60 mg/m2/day) for four consecutive days, approximately every 4 weeks. While the oral administration of mel-phalan is convenient, absorption can sometimes be unpredictable,19 and therefore the dose may need to be titrated upward in subsequent cycles, until modest myelosuppression (i.e., absolute neutrophil count — 1000/MM3 weeks after the start of the cycle) is seen. Also, in patients with renal insufficiency, pronounced cytopenias can develop with full melphalan dosing, and a starting dose of 4-6 mg/m2/day for 4 days is recommended, with careful monitoring of hematologic toxicity. Objective responses, usually occurring within the first two to three cycles of MP, can be expected in 50-60% of patients and last on average 1.5-2 years.20 Because of the low toxicity and ease of administration of oral MP, it is often selected as the initial therapy in

Table 83.2

Dosage schedules for VAD and related reg

imens

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