Response rate, remission duration, and survival time were compared in 236 patients with multiple myeloma receiving a melphalan‐prednisone‐procarbazine combination and in 156 patients receiving only melphalan‐prednisone. Response was confirmed when myeloma protein production had been reduced to less than 25% of the pretreatment value. Of the evaluable trials, 59% of patients responded to the procarbazine combination, and 48% to melphalan and prednisone. In both treatment groups, the survival time of all patients (22 months) and the remission duration of responding patients (21 months) were similar. Maximum degrees of myeloma protein reduction were associated with longer remissions and survival. Previously reported resistance to treatment of patients with only lambda Bence Jones protein was not apparent with these superior treatment regimens. Results support the value of combination chemotherapy with melphalan‐prednisone‐procarbazine for remission induction in patients with multiple myeloma.

The effect of certain disease parameters on remission and survival time was evaluated in 482 patients with multiple myeloma treated with intermittent courses of melphalan–prednisone combinations. Increasing degrees of anemia, hypercalcemia, azotemia, and high serum myeloma protein levels were associated with progressive lifespan shortening. The short survival of patients with anemia and hypercalcemia was associated with short remissions in responding patients with these abnormalities. The extent of tumor mass was defined from specific laboratory parameters reported by Durie12 to be associated with large numbers of plasma cells. More advanced stages of myeloma were associated with higher frequencies and degrees of normal immunoglobulin depression. The response rate was not affected by the tumor mass grade, but increasing tumor mass was associated with a shorter lifespan. Greater degrees of tumor reduction were associated with longer remission and survival times. Patients in whom a marked tumor reduction was rapid had shorter survival and remission times than patients who responded more slowly.

A combination of intravenous cyclophosphamide and vincristine (Oncovin) and oral prednisone (COP) was given every 2 weeks to 262 patients with disseminated Hodgkin's disease, lymphosarcoma, reticulum cell sarcoma, and follicular lymphoma. A complete remission was produced in 36% of patients with Hodgkin's disease, 50% of patients with lymphosarcoma, and 39% of patients with reticulum cell sarcoma. These remission rates are significantly superior to those produced by single agents. Patients who achieved a complete remission were randomly allocated to monthly COP (maintained remission) or to no treatment (unmaintained remission). The median duration of maintained remission was longer than unmaintained remission for Hodgkin's disease (42 weeks vs. 19 weeks) and lymphosarcoma (49 weeks vs. 21 weeks) but not for reticulum cell sarcoma (24 weeks vs. 25 weeks). The duration of remission for patients with little or no prior therapy was compared to that for patients in a similar study in which single agents were used.4 For lymphosarcoma and reticulum cell sarcoma, remissions maintained with COP were longer than remissions maintained with cyclophosphamide. For Hodgkin's disease and lymphosarcoma, unmaintained remissions after COP induction were longer than after single agent induction. All parameters of response, that is, complete remission rate, duration of remission, and survival were adversely affected by major prior treatment with radiotherapy and chemotherapy. The initial response to treatment correlated positively with survival. The survival of patients with lymphosarcoma or reticulum cell sarcoma receiving COP treatment was significantly superior to a comparable group of patients treated sequentially with single agents.

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