title: Phase I-II trial of high-dose melphalan in previously untreated stage III multiple myeloma: Cancer and Leukemia Group B study 8512.
abstract: To study the efficiency of high-dose melphalan in previously untreated patients with advanced myeloma, we performed a Phase I-II trial. Twenty-eight patients were treated at dose level of 60-140 mg/m2. Each patient was first treated with a priming dose of cyclophosphamide (300 mg) followed by high-dose melphalen 1 week later. One course of therapy was given. Patients were then followed without further therapy until relapse. Clinical and laboratory features of the 28 patients in this study included: median age 63, performance status 0-2, hypercalcemia 21%, bone pain 82%, paraprotein types: IgG 76%, Iga 20%, and paraproteinuria 71%. Because none of the patients achieved complete remission (CR) at 60 mg/m2, despite life-threatening toxicity in all patients, the dose level was rapidly increased to 140 mg/m2, a dose previously reported to induce a high percentage of CR. At this dose, CR was achieved in only 1 of 11 patients (9%). This patient had multiple plasmacytomas without generalized bone marrow involvement. One additional patient at 100 mg/m2 achieved CR. Of the whole group, 12 achieved PR. Durations of remissions were generally short: CR 6.3 and 18+ months and PR 2.3-18 month, median 6.9 months. Life-threatening myelosuppression was universal with prolonged pancytopenia. Treatment-related deaths from sepsis were observed in 29% of patients. The median survival of the entire group was 15.6 months. Older patients in this trial did not tolerate high-dose melphalen therapy well; this resulted in a high proportion of toxic deaths and poor overall survival.
authors.affiliation: Department of Medicine, Maine Medical Center, Portland.
authors.forename: D C
authors.initials: DC
authors.lastname: Case
authors.forename: M
authors.initials: M
authors.lastname: Coleman
authors.forename: A
authors.initials: A
authors.lastname: Gottlieb
authors.forename: K
authors.initials: K
authors.lastname: McCarroll
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D012074:Remission Induction
chemical_list: D008558:Melphalan