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The southwest oncology group tested cis-platinum, given in 28-day courses of 50 mg/m2 twice, a week apart, in patients with epidermoid carcinoma of the esophagus. Currently 19 patients entered on the study are evaluable for response (15 fully evaluable). Of these, two attained complete disappearance of tumor and four had partial responses. Of the remainder, two had stable disease lasting in excess of 90 days. Hematologic toxicity has been minimal except that three patients required multiple blood transfusions for anemia not due to blood loss. Of 21 patients currently evaluable for renal toxicity, nine had mild, and three had moderate azotemia. These results suggest that, unlike what has been believed in the past, squamous cell carcinoma of the esophagus is not a chemotherapy-resistant tumor. Further evaluation of cis-platinum alone and in combination with radiotherapy and surgery are in progress.

The FAM combination with the simultaneous administration of 5-fluorouracil, doxorubicin, and mitomycin C is considered standard chemotherapy for gastric adenocarcinoma. This study was initiated to determine whether a kinetically designed sequential administration of these three drugs would be superior and whether the presence or absence of easily measurable tumor would imply differences in survival. To do so, the Southwest Oncology Group tested two schedules in a randomized study of 239 patients. Independent judgments of response were made by two authors with the same results. Equivalent response rates (23% of all eligible sequential and 30% simultaneous) and median survival durations (22 and 23 weeks, respectively) were seen. Patients with and without readily measurable tumors each lived a median of 22 weeks. Higher degrees of hematologic toxicity were associated with prolonged survival (median 27 weeks versus 20 weeks, p = 0.04). Patients treated by community oncologists were described as having higher response rates than those treated in major medical centers (64% versus 31%, p = 0.03). The meaning of this is questionable in that there were no statistical differences in survival or toxicity. Those with prior exposure to 5-fluorouracil had only a tendency, without statistical significance, for a slightly inferior response and survival.

The Southwest Oncology Group (SWOG) colorectal adjuvant study 7510 went through two phases. From 1975 to 1977, 309 patients were randomized to chemotherapy alone or the same chemotherapy plus immunotherapy. From 1977 until 1980, 317 patients were randomized among the same two therapy programs and a control group. With a minimum follow-up in either phase of greater than 7 years, data are now mature. They show no difference in relapse-free survival (RFS) nor overall survival (OS) in either the two-way phase or in the three-way phase. There is no indication, except possibly in one very small subset, that the addition of immunotherapy to chemotherapy provides an improvement in OS or in RFS. Using data from patients accrued after randomization to the control group, we fail to find evidence that either chemotherapy alone or chemoimmunotherapy improves OS or RFS when contrasted to outcomes obtained by patients on the control arm. In fact, we have significant evidence, at the P = .016 level, that chemotherapy does not improve OS by at least 50%; we also have significant evidence, at the P = .011 level, that chemoimmunotherapy will not improve OS by at least 25%. No evidence of efficacy was demonstrated for either treatment regimen, even though enough therapy was given to result in significant toxicities. Acute toxicity was at least moderate, but not fatal, in 75% of patients. Recognizable delayed toxicity included rare cases of fatal renal failure and acute leukemia.

Porifiromycin has been tested in many groups of patients over the past several years (1-7). This report is an analysis of greater than 100 patients with epidermoid and urinary tract transitional cell carcinomas treated with this agent. A review of these data and the available literature on this agent shows that porfiromycin offers definite usefulness in disseminated squamous cell carcinomas of the cervix, and definite but lesser effectiveness in epidermoid carcinomas of the lung, the head and neck region, and other sites. Responsiveness was also demonstrated in transitional cell carcinomas of the urinary tract. Toxicity was tolerable and consisted primarily of myelosuppression and local skin necrosis in sites where extravasation had occurred.

Because "the standard" chemotherapy for advanced gastric adenocarcinoma, the FAM combination of 5-fluorouracil, adriamycin, and mitomycin, is only minimally effective, there is a clear need for other choices. Therefore, the Southwest Oncology Group tested the new adriamycin analog, bisantrene, hoping that it might be more effective than the "parent drug." Twenty-six patients with gastric adenocarcinoma were treated on a program of every-3-week 2-hour bisantrene infusions. The starting dose was 260 mg/m2 (208 if poor risk), with subsequent doses based on prior toxicity. The regimen caused sufficient toxicity (especially local phlebitis with pain and swelling) to assure an adequate test. One person (3.8% of eligible patients) experienced a clinically useful 3-month response. He had previously had progressive disease on FAM. Nevertheless, we conclude that bisantrene is not an addition to the small list of drugs useful in the management of gastric adenocarcinoma.

The question was raised whether routine splenectomy might, by virtue of its effects on the receipt of subsequent chemotherapy, offer long-term benefits to patients with advanced Hodgkin disease. Therefore, we compared followup data from a group of patients who were receiving mechlorethamine hydrochloride, vincristine sulfate, procarbazine hydrochloride, and prednisone (MOPP regimen) and who had had splenectomies to a group of similarly treated, carefully matched control patients on the MOPP regimen who had not had splenectomies. Our results indicate no important difference in duration of survival or long-term remission status. There was only a suggestion that splenectomy in such patients may be followed by impaired resistance to subsequent infections. Therefore, although early splenectomy can be important in the assessment of splenic disease, it must not be considered to be a therapeutic procedure per se.

Ifosfamide was administered to 21 patients with recurrent or disseminated lung cancer at a dose of 4.0 gm/M2 iv every 3 weeks. The response rate was 33% with an additional 14% showing no response or stable disease. At a dose of 1.2 gm/M2 daily for 5 days every 4 weeks, 57% of 14 patients responded with 35% showing no response or stable disease. The majority of the patients (28) had epidermoid carcinoma. Two (7%) had complete response with 9 (32%) showing partial responses. Other responses included 1/2 oat cell carcinomas and 3/6 large cell undifferentiated carcinomas. Toxicity was equal in both regimens for nausea, vomiting, increased serum LDH and neutropenia but the 5 day program had significantly less hemorrhagic cystitis. Survival was greatly influenced by response. There was no statistical difference in overall length of response between responders and the non responding/stable disease patients. But these two groups had a very significant survival advantage when compared to those patients with increasing disease. Similarly, there was a significant improvement in response duration for the low dosage regimen. Therefore, the low dose 5 day regimen is recommended because of its response rate, it has less hemorrhagic cystitis and it has better patient acceptance in that it can be given as an outpatient and does not require a Foley catheter.

Two hundred twenty eligible patients with metastatic colorectal carcinoma were treated with a combination of beta-2'-deoxythioguanosine (BTG), plus methyl-CCNU or mitomycin. There was no significant difference in overall response (CR/PR + stable) among fully evaluable patients between the mitomycin plus BTG arm 19/96 (19.7%) and the MeCCNU arm 26/87 (29.8%). Median survival of eligible patients was 19 weeks with mitomycin plus BTG versus 21 weeks with MeCCNU plus BTG: no difference. Median survival of responders (40 weeks) and patients with stable disease (35 weeks) was significantly better than patients with increasing disease (17 weeks): p + 0.001.

The SWOG carried out a Phase II evaluation of rubidazone in patients with advanced breast cancer. Good risk patients were given rubidazone 150 mg/m2 IV every three weeks. Poor risk patients were given a 25% dose reduction at the start of treatment. Rubidazone dose was increased or decreased depending on toxicity. One patient went into complete remission, four had partial remission and nine had stable disease. Forty-two patients showed increased disease on treatment. No cardiotoxicity was seen, but other common toxicities noted included mostly mild to moderate myelosuppression, nausea, vomiting and alopecia. This study failed to indicate significant antitumor activity of rubidazone in patients with advanced breast carcinoma.

Twenty-three patients with advanced heavily pretreated epithelial carcinoma of the ovary were treated with m-AMSA. Eleven patients received a mean of 2.3 courses at a dose of 40 mg/m2 X 3 days q 21 days and 12 patients received a mean of 4.3 courses at a dose of 30 mg/m2 X 3 days q 21 days intravenously. One (5%) partial response in 22 fully evaluable patients was observed. Toxicity was mild and well tolerated. We conclude that m-AMSA is a relatively inactive drug in the treatment of epithelial ovarian carcinoma.

The Southwest Oncology Group tested an outpatient Cis-platinum regimen in patients with carcinoma of the head and neck. Courses which consisted to two doses, a week apart, were scheduled to be given at 4-week intervals. Eighty-nine poor risk head and neck cancer patients, who had received extensive prior therapy with surgery, radiation, and/or multiple drugs were studied. Sixteen (18% of all entered and 25% of the 65 fully evaluable) had objective tumor regression. The median duration of response was 136 days. Toxicity was moderate. Myelosuppression was minimal with only 3% of patients exhibiting leukocyte nadirs below 2,000 and less tha 2% experiencing platelet counts below 50,000. Significant, but reversible, impairment of renal function occurred in 8% of patients. Individual susceptibility to such renal toxicity appears to have been predictable. This simple outpatient program with its effectiveness and minimal toxicity in poor risk patients deserves further utilization.