Robert W. Talley

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.

Four hundred and seventy-two patients with disseminated neoplasia were treated with two or more doses of adriamycin. The initial dose for “good risk” patients was 75 mg/m2 every 3 weeks, and for “poor risk” patients was 60 mg/m2 every 3 weeks. Objective remissions were seen in 118/472 patients, with best results noted in lymphomas (21/48), sarcomas (21/64), and carcinoma of the breast (16/50). Eighty-nine per cent of remissions occurred within three courses. Hematopoietic toxic effects were seen in 73% of patients; nausea, vomiting, and/or stomatitis were observed in 43%. Changes in electrocardiograms were seen in 42/472 patients after cumulative doses of adriamycin ranging from 45 mg/m2 to 600+mg/m2. Irreversible congestive heart failure occurred in two patients after cumulative doses of 555 mg/m2 and 825 mg/m2, respectively. It is concluded that adriamycin is an active agent, most remissions occur promptly, and significant cardiotoxic reactions appear to be cumulative.

The effect of dose and schedule of arabinosyl cytosine (ara-C) on bone marrow function and antitumor response was evaluated in 88 patients with metastatic cancer. It was found that: ( a ) Single doses of ara-C produced no myelosuppressive or antitumor effect. ( b ) Continuous infusion for 48 or 96 hours resulted in a steep dose-response curve with respect to marrow depression; 18–38% of analyzable patients had tumor regression. ( c ) Continuous infusion for 24 hours produced an increase in marrow depression with doses up to 1200 mg/sq m, after which further increase in dose did not produce greater myelosuppression. Tumor regression occurred in 10% of these patients. The above dose-marrow response curves, interpreted with a background of experimental data, suggest that a substantial nonproliferating marrow stem cell pool exists in man. ( d ) Granulocytopenia was more frequent than thrombocytopenia, and lymphopenia did not occur. Platelet “rebound” to greater than 1,000,000 per cu mm following myelosuppression was common. The cell kinetic and therapeutic implications of these observations are discussed.

Improved modalities to treat metastatic renal cell carcinoma will require an aggressive surgical and chemotherapeutic approach. Nephrectomy with hormonal and non-hormonal chemotherapy does improve median survival and 3-year survival significantly. The use of xenogeneic specific immune ribonucleic acid and Bacillus Calmette-Guerin offers promising immunotherapeutic modalities that may be combined with surgical and chemotherapeutic regimens. Early diagnosis of metastatic disease is important to evaluate properly the results of various modalities of treatment and possibly to improve the efficiency of these modalities. The management of solitary metastatic nodules should involve aggressive resection of the primary and metastatic nodule. Adjuvant hormonal and non-hormonal chemotherapy should be considered in all stages of the disease.

In a randomized and stratified study, 294 patients with advanced gastrointestinal cancer were treated either with 5-fluorouracil (5-FU) 400 mg/m2 weekly intravenously (i.v.) or 5-FU 400 mg/m2 i.v. weekly plus methyl-CCNU 175 mg/m2 orally (p.o.) every 6 weeks. The response rate in colorectal cancer with 5-FU was 9.5% while the two-drug treatment produced a response of 31.8% (p=.009). The response in all gastrointestinal cancers to 5-FU was 10.6% as compared with29.3% for the combination (p=.012). All responses were partial. The two-drug regimen is more effective and more toxic than weekly 5-FU therapy.