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.
To study the influence of chronologic age on treatment outcome in patients with advanced, diffuse large-cell (histiocytic) lymphoma (DHL), we reviewed the results of two recent Southwest Oncology Group (SWOG) clinical trials. From 1974 to 1982, members entered 307 eligible patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without bleomycin, and CHOP with or without immunotherapy using BCG, levamisole, or both. Complete response (CR) rates declined progressively with advancing age: 65% in those under 40, 60% in the 40 to 54 age group, 55% in the 55 to 64 age group, and 37% in those 65 and older (P = .001). Likewise, survival decreased significantly in older patients: medians were 101 +, 52, 34, and 16 months, respectively (P less than .001). Treatment guidelines included an initial dose reduction of 50% for patients aged 65 or older and for younger patients with bone marrow compromise. Despite protocol specifications, 23 of 81 patients aged 65 or older received initial full-dose therapy. When these patients were compared with younger patients on whom full-dose chemotherapy was started, survival curves, but not CR rates, were still significantly different. There were no significant differences in duration of CR or frequency of treatment complications. These data suggest that older age is associated with a worse prognosis in advanced DHL. Moreover, the initial dose reduction for patients aged 65 or older may have contributed to their inferior outcomes.
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.
Deoxycoformycin (dCF), a potent inhibitor of adenosine deaminase (ADA), was explored for its antineoplastic potential in 28 patients with advanced lymphoid malignancy. Both normal and malignant B lymphocytes have low levels of ADA activity, and low doses of dCF profoundly inhibit this enzyme in the peripheral blood of patients with chronic lymphocytic leukemia (CLL). The low doses of dCF administered in this trial (4 mg/m2) were not associated with prohibitive toxicity. Five of 28 patients had an objective response. Four additional patients had clinical improvement. No significant difference in the pretreatment ADA activity existed between responding patients and treatment failures. The demonstration of responses to dCF following failure on standard alkylating agents suggests that dCF may not be cross-resistant with current agents used to treat CLL. Additional studies should be pursued using low-dose dCF in patients with advanced malignancy.
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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