Three combination chemotherapy regimens each with or without the methanol-extracted residue of bacillus Calmette-Guérin (BCG) (MER) were compared for efficacy. After stratification for disease-free interval and dominant sites of disease, patients were randomized to either CMF (cyclophosphamide [CYC], 100 mg/m2 orally, days 1 through 14; methotrexate [MTX], 40 mg intravenously [IV], days 1 and 8; 5-fluorouracil [5-FU], 500 mg/m2 IV, days 1 and 8), or CAF (CYC, 100 mg/m2 orally, days 1 through 14; doxorubicin [DOX], 25 mg/m2 IV, days 1 and 8; 5-FU, 500 mg/m2 IV, days 1 and 8), or CAFVP (CAF as above plus vincristine [VCR], 1.0 mg/m2 IV, days 1 and 8; and prednisone [PRED], 40 mg/m2 orally, days 1 through 14). Nonspecific immunotherapy with MER was administered in five sites at 100 micrograms or at the lowest tenfold dilution that produced a 1-cm indurated lesion. A total of 432 patients were entered, but 37 were disqualified, leaving 395 evaluable for treatment results and toxicities. One hundred thirty-five evaluable patients were randomized to chemoimmunotherapy until October 28, 1978. One hundred twenty-six evaluable patients were randomized to chemotherapy alone in the same time period. For the entire study, a total of 260 evaluable patients were randomized to chemotherapy. Chemoimmunotherapy patients were compared with the initial 126 chemotherapy patients. Chemotherapy regimens were compared among all 260 patients. Patient characteristics were similar between regimens and between chemotherapy and chemoimmunotherapy treatment groups. For patients on chemotherapy plus MER, there was no significant differences between the regimens for response frequencies: 43%, 41%, and 32%, respectively for CMF, CAF, and CAFVP. The comparable chemotherapy alone group had 36%, 58%, and 63% response, respectively. The response rates, adjusted for chemotherapy regimen, were 52% and 38% (P = .02) for chemotherapy and chemoimmunotherapy, respectively. MER was associated with painful ulcers and fevers. Thus, MER produced toxicity without response or survival benefit and further randomization after October 28, 1978 was to chemotherapy alone. For 260 evaluable patients on chemotherapy alone, the complete (CR) and partial responses (PR) were 37%, 55%, and 58%, respectively for CMF, CAF, and CAFVP. These response rates for CAF and CAFVP were significantly better than CMF (P = .01 and P less than .01, respectively). These comparisons were consistent within subgroupings such as dominant sites of disease.(ABSTRACT TRUNCATED AT 400 WORDS)

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Forty-one patients with newly diagnosed small cell anaplastic lung cancer were evaluated for abnormalities in water homeostasis. Each patient underwent a standard water load (SWL) test. Overall, 68% had abnormalities in the SWL test. Abnormalities were found in 47% of the patients with carcinoma clinically limited to one hemithorax and in 86% of the patients with more extensive carcinoma. The determination of urinary antidiuretic hormone levels was available for 27 patients. Abnormally elevated levels were found in 44% of those patients. Forty-six patients had clinically detectable syndrome of the inappropriate secretion of antidiuretic hormone (SIADH); in 12% of patients water restriction was necessary. The incidence of detectable abnormalities in water homeostasis in this study was higher than has been previously recognized. The SWL test is a sensitive and useful means of determining the presence of impaired water handling in patients with small cell carcinoma of the lung.

In 1978, Cancer and Leukemia Group B initiated a randomized study to determine the usefulness of the addition of bleomycin and/or high-dose methotrexate to standard therapy for the treatment of certain adult non-Hodgkin's lymphomas. Between 1978 and 1985, 177 patients with diffuse large cell lymphoma (DLCL) and 97 patients with other intermediate-grade non-Hodgkin's lymphoma were randomized to receive therapy with three courses of cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) every 3 weeks with or without low-dose bleomycin by continuous IV infusion. Responders after three courses were further randomized to 3 weeks of therapy with either high-dose methotrexate (3 gm/m2/week intravenously with leucovorin rescue) or standard-dose methotrexate (30 mg/m2/week orally without rescue). Therapy was concluded with three additional courses of CHOP. Neither the addition of low-dose infusion bleomycin nor the use of high-dose rather than low-dose methotrexate had significant effects on response for patients with DLCL; complete response rates for the four treatment programs ranged from 47% to 51%. Median failure-free survival (FFS) for the entire group of DLCL patients was 12 months; 5-year FFS was 27%. There was no significant effect on FFS from the addition of either low-dose bleomycin to CHOP (5-year FFS: CHOP, 28%; CHOP-B, 26%, P = 0.81), or from the use of different doses of methotrexate (5-year FFS: high-dose, 34%; standard-dose, 33%, P = 0.51). Patients with follicular large cell lymphoma, with or without diffuse areas, had a better FFS (5-year FFS, 47%) than patients with DLCL (5-year FFS, 27%), while the patients with the other histopathologic subtypes of diffuse lymphomas had the poorest FFS (5-year FFS, 16%).

In a prospective, randomized trial Cancer and Leukemia Group B (CALGB) evaluated CAF chemotherapy (cyclophosphamide + doxorubicin + 5-fluorouracil [5-FU]) v CAF plus tamoxifen (TCAF) in advanced breast cancer. Patients were stratified by estrogen receptor (ER) status, dominant site of metastatic disease, menopausal status, and prior adjuvant therapy. Regardless of ER status or menopausal status, the addition of tamoxifen conferred no significant advantage in response rate, response duration, time to treatment failure (TTF) or survival over CAF alone. A secondary objective was to compare the response to CAF of ER positive (ER+) and ER negative (ER-) patients to determine if there was a differential response to cytotoxic chemotherapy. Response rates of ER+ and ER- patients to CAF were identical (56%), but the response duration, time to treatment failure, and survival of ER+ patients were significantly longer than ER- patients. This lack of differential response implies that chemotherapy and hormonal therapy may compete for the same pool of ER+ cells. It also suggests that chemotherapy kills breast cancer cells indiscriminately, regardless of ER status.