Is More Better?
Abstract
Cancer Investigation, l q l ) , 93-94 (1992) EDITORIAL Is More Better? M. Robert Cooper, M.D. Melphalan remains the single most effective oral chemotherapeutic drug used to treat multiple myeloma. A major problem with the oral administration of the drug is its variable bioavailablity. The presence of an L-phenylalanine moiety in the structure of melphalan makes it likely that gastrointestinal absorption occurs through normal amino acid transport mechanisms and that the presence of food influences the drug's uptake. Another factor that complicates the bioavailability of this agent is the fact that melphalan undergoes spontaneous hydrolysis at physiologic pH. Although the clinician attempts to circumvent this problem by increasing the dose of melphalan until hematologic toxicity is observed, the effect of the increased dose will not become apparent for some 4-6 weeks. And in some patients, particularly those with aggressive myeloma this delay in the delivery of an effective dose of melphalan may prove deleterious. The intravenous use of the drug has been extensively investigated, but this route of drug administration has never been shown to be superior to oral dosing. One approach taken with intravenous melphalan has been to give it in large or single doses to