Combination chemotherapy with CHOP (cyclophosphamide, Adriamycin, vincristine, and prednisone) and HOP (Adrimycin, vincristine, and prednisone, was used as treatment for patients with pathologically staged, advanced non-Hodgkin's lymphoma. Among 204 evaluable patients treated on CHOP there were 71% complete remissions with 92% overall responses. Among the 216 evaluable patients on HOP there were 61% complete remissions and 88% responses. Complete remission rates among patients with histiocytic lymphoma were comparable to those of patients with lymphocytic disease. Patients with nodular lymphoma had higher rates of complete remission than their counterparts with diffuse lymphoma. This was noted with both CHOP (78% vs. 67%) and HOP (67% vs. 60%) induction therapy. Rapid responses were common, as more than 14% of complete remissions and 66% of overall responses were achieved with the first course of treatment. Patients in complete remission have been maintained with either cyclophosphamide, vincristine, and prednisone (COP) or arabinosyl cytosine, vincristine, and prednisone (OAP). After 1 year, 86% of patients on COP and 80% on OAP are projected to be free of disease.
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.
Previously untreated patients with multiple myeloma were entered on a randomized clinical trial to determine whether the use of alternating combination chemotherapy, including vincristine, doxorubicin, alkylating agents, and prednisone (160 patients) was more effective than conventional chemotherapy with melphalan and prednisone (77 patients), and whether the addition of the immunomodulating agent levamisole to maintenance chemotherapy enhanced the survival of patients achieving remission. The treatment groups were well matched for all major factors. The more aggressive chemotherapy was more effective at inducing remission, with a significantly higher proportion of patients achieving at least 75% tumor mass regression (53% with alternating combinations versus 32% with melphalan-prednisone, p = 0.002). Furthermore, the median survival was increased to 43 months with alternating combination chemotherapy as compared to 23 months with melphalan-prednisone (p = 0.004). After six to 12 months of induction therapy, 84 patients achieving remission were rerandomized to receive maintenance chemotherapy alone or with the addition of levamisole. The survival from the start of maintenance therapy was longer in patients receiving the added levamisole than with chemotherapy alone (p = 0.01). These findings support the use of aggressive multiagent chemotherapy for remission induction in patients with advanced-stage multiple myeloma.
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