Weekly low-dose cyclophosphamide and alternate-day prednisone: an effective low toxicity regimen for advanced myeloma

10 of 20 patients with advanced myeloma treated with a simple regimen consisting of weekly low-dose cyclophosphamide (C; 150-300 mg/m2; maximum weekly dose = 500 mg) given intravenously or orally, and alternate-day oral prednisone (P; 50-100 mg) responded clinically and with a fall in serum M protein greater than 50% or urine M protein greater than 90%. 3 of these responders were previous primary treatment failures, all having received cyclophosphamide in combination with other drugs given at 3- to 4-wk intervals. 2 patients treated with this regimen as primary therapy also responded. Although the median survival for the 10 responders was reached at 24.5 months, 3 patients remain alive and well 50+ months from the start of CP therapy. An additional 5 patients had disease stabilization or major improvement in bone pain and/or pancytopenia for over 12 months despite failure to meet strict criteria for response. The data suggest that disease control may be achieved by the more frequent scheduling of known active drugs such as cyclophosphamide (although it alone or in combination with other drugs may be ineffective when given at standard 3- to 4-wk intervals) in combination with prednisone or a more continuous basis. This is an effective yet simple therapeutic approach to myeloma with the distinct advantage of less toxicity than the multiple drug regimens in current use. It may have particular applicability to patients who are elderly or debilitated or in patients in whom cytopenia is present initially or develops on standard melphalan/prednisone regimens.