Interferon alfa-2b/melphalan/prednisone in previously untreated patients with multiple myeloma: a phase I-II trial.
Interferon alfa-2b (Intron A; Schering Plough) has been shown to be active in advanced previously treated multiple myeloma (MM). Recent in vitro evidence has suggested synergy between cytotoxic agents and interferon alfa-2b. This phase I-II protocol was initiated to study interferon alfa-2b in combination with melphalan and prednisone. Groups of five patients received interferon alfa-2b twice-weekly for two weeks at dose levels of 0.5, 1.0, 2.0, 5.0 and 10.0 X 10(6) IU/m2. During week 2, melphalan (9 mg/m2) and prednisone (40 mg/m2) were administered concurrently with interferon alfa-2b followed by a rest period during nadir myelosuppression, the cycles being repeated every 28 days. Thirty patients were entered of whom 21 were Stage III, 3 Stage II and 6 Stage I. Median nadir WBC/mm3 and platelets/mm3 at the various dose levels are given in the table. Serious adverse reactions while on study included myocardial infarction, renal failure and leukopenia-related sepsis. Early response information is available. Twenty-six patients are evaluable for response. Seven have had progressive disease and 19 (69%) a partial response, the median duration was 11+ months. Interferon alfa-2b does not appear to antagonize melphalan/prednisone effectiveness and may be additive or synergistic. Full evaluation of this combination will be undertaken in randomized controlled trials which are now underway.
D058186:Acute Kidney Injury / Q000139:chemically induced; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004341:Drug Evaluation; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000009:adverse effects / Q000627:therapeutic use*; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008558:Melphalan / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D009203:Myocardial Infarction / Q000139:chemically induced; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use*; D018805:Sepsis / Q000150:complications
D007370:Interferon Type I; D008558:Melphalan; D011241:Prednisone