Phase II evaluation of mitoxantrone in advanced pancreatic carcinoma: a Southwest Oncology Group study.

Patient with advanced adenocarcinoma of the pancreas and no prior chemotherapy were treated on a Phase II trial of mitoxantrone. Doses were adjusted for hepatic dysfunction as defined by bilirubin. Twenty-four patients with a bilirubin less than or equal to 1.5 mg% received mitoxantrone 12 mg/m2 i.v. repeated every three weeks. Myelosuppression in the form of leukopenia was the major toxicity. There were no responses in twenty-four evaluable patients.

Randomized comparisons of radiotherapy and carmustine versus procarbazine versus dacarbazine for the treatment of malignant gliomas following surgery: a Southwest Oncology Group Study.

Between 1977 and 1981, the Southwest Oncology Group entered 278 patients on a randomized study (SWOG 7703) to compare the effect of three different chemotherapeutic agents given in combination with radiotherapy (6000 rads over 7 weeks) following surgery for malignant gliomas. The chemotherapy regimens were: carmustine (BCNU)--80 mg/m2 iv daily X 3 every 6 weeks; procarbazine (PCB)--100 mg/m2 orally; or dacarbazine (DTIC)--175 mg/m2 iv daily X 5 every 4 weeks. Patients were stratified according to age, and degree of resection, with no differences identified between groups. The response rates (complete plus partial) for BCNU and DTIC were significantly better than for PCB [BCNU, 39%; PCB, 13%; and DTIC, 38% (P less than 0.01)]. The response duration and survival were somewhat better in patients treated with BCNU and DTIC, but compared to patients treated with PCB, the difference was not statistically significant. Median survival times were: BCNU, 45 weeks; PCB, 31 weeks; and DTIC, 49 weeks (P greater than 0.3). There were six toxic deaths with BCNU and four with PCB, most of which were due to infection associated with leukopenia. The high toxicity and minimal benefit of chemotherapy added to radiotherapy compared to historical results with radiotherapy alone suggest that combined treatment may not be indicated for some patients.

An evaluation of the effect of vincristine added to cyclophosphamide, 5-fluorouracil, methotrexate, and prednisone in advanced breast cancer.

A multi-institutional randomized clinical trial was carried out to evaluate the effect of vincristine (V) added to cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP) for the treatment of metastatic breast cancer. There were 427 patients entered into the study and randomly assigned to one of the two treatments, i.e. the five drug therapy CMFPV or the four drug therapy CMFP. The differences in patient survival and tumor response between the two treatment groups were not statistically significant. The data were also analyzed using multivariate procedures to determine those factors ascertained at entry into the study which were predictors of survival or predictors of response to therapy. The one factor that predicted both response and survival was performance status. An additional important predictor of survival was sites of metastatic involvement. Other significant predictors of response were menopausal age, BUN, and hematocrit.

Drug combinations in the treatment of gastric adenocarcinoma: a randomized Southwest Oncology Group study.

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.

Phase II trial of methyl-GAG (NSC-32946) in squamous cell and adenocarcinoma of the lung.

Thirty-four assessable patients with advanced squamous cell and adenocarcinoma of the lung were treated with weekly MGBG in a phase II trial. Only one partial response, in adenocarcinoma, was observed. Myelosuppression was mild to moderate. Major toxicities consisted of myalgia, myopathy, mucositis, gastrointestinal and pronounced vasculitis in one patient. It would appear that MGBG does not have sufficient antitumor activity to warrant further investigation in advanced squamous cell and adenocarcinoma of the lung.

Clinical trial of chlorozotocin, DTIC, and dactinomycin in metastatic malignant melanoma.

Thirty evaluable patients with metastatic malignant melanoma were treated with a combination of chlorozotocin, DTIC, and dactinomycin. One complete and four partial responses were achieved, for an overall response rate of 17%. Cumulative myelotoxicity was noted, as well as universal gastrointestinal intolerance. One patient developed probable drug-related nephrotoxicity. A survival advantage was noted for responding patients. We conclude that the addition of chlorozotocin did not improve response rate or response duration and that further trials with this drug combination cannot be recommended.

Phase II study of AMSA in lung cancer.

Ninety-one assessable patients with advanced oat cell and non-oat cell carcinoma of the lung were given AMSA on an intermittent every-3-week schedule. Starting doses ranged from 55 to 120 mg/m2, depending on the presence and severity of hepatic dysfunction. Three partial responses (two squamous cell carcinomas, one adenocarcinoma) of short duration were documented. The major toxic effect was leukopenia (44%). AMSA does not appear to have sufficient antitumor activity to warrant further investigation in advanced lung cancer.

Combination chemotherapy with mitomycin C, adriamycin, and cyclophosphamide in advanced adenocarcinoma and large cell carcinoma of the lung.

Thirty-six patients with advanced carcinoma of the lung (30 with adenocarcinoma and six with large cell carcinoma) were treated with a combination of mitomycin C, Adriamycin, and cyclophosphamide (MAC) in a phase II study. Seven partial remissions were observed in adenocarcinomas, while none were seen in large cell carcinomas. The survival of patients in remission was clearly prolonged (P less than 0.01), with responders living a median of at least 39 weeks compared to 17 weeks for nonresponders. The combination was well-tolerated with moderate anorexia, nausea, vomiting, and alopecia. Myelosuppression was manageable but was more pronounced in previously chemotherapeutically treated patients. MAC offers a reasonable response rate in patients with adenocarcinoma of the lung with significant prolongation of survival; however, there was no significant advantage when compared to mitomycin C used as a single agent.

The value of serial carcinoembryonic antigen (CEA) in predicting response rate and survival of patients with gastrointestinal cancer treated with chemotherapy.

Elevated serum levels of carcinoembryonic antigen (CEA) were found in 70% of 141 patients with advanced gastrointestinal (GI) cancers. Serial CEA measurements were performed on 70 patients before and during chemotherapy. The majority were treated with 5-FU and Methyl-CCNU (33 patients), 5-FU (19 patients), or 5-FU and mitomycin-C (8 patients). In 49 patients with colorectal carcinoma who had elevated serum CEA prior to chemotherapy, 18 had objective partial tumor remission, 16/18 (89%) showed definite decrease in CEA level, one had no change, and one had an increase CEA titer. Thirty-one patients had either stable disease (10 patients) or increasing disease (21 patients) while on chemotherapy. Of these patients four showed decrease in CEA, eight had no change, and 19 had increase in CEA levels as compared to pretreatment value. The survival of patients with a decrease in CEA during chemotherapy was statistically significant (p = .03) as compared to survival of those with no change or increasing CEA levels. In 21 patients with other GI cancers, the correlation between the clinical response and change in CEA level observed was not as definite as in patients with colorectal carcinoma.

Phase II evaluation of cis-dichlorodiammineplatinum(II) in advanced malignancies of the genitourinary and gynecologic organs: a Southwest Oncology Group Study.

One hundred and forty-seven fully and partially evaluable patients with advanced measurable malignancies of the genitourinary and gynecologic organs were given cis-dichlorodiammineplatinum(II) at a dose of 75 mg/m2 iv every 3 weeks. Thirty-six patients with testicular neoplasms were studied; five complete responses (13.9%) and seven partial responses (PR) (19.4%) were noted. Thirty-seven patients with ovarian adenocarcinoma were evaluated; five PRs (13.5%) were seen. One complete response (11.1%) and two PRs (22.2%) were obtained among nine patients with urinary bladder cancer. Four PRs (19.0%) were seen among a group of 21 patients with advanced prostate cancer. One PR (4.8%) was noted among 21 patients with renal cell cancer and no responses were seen in eight patients with cervical cancer. There was a highly statistically significant (P less than 0.001) survival advantage for the responding testicular tumor patients. Toxicity was similar to that previously reported, with gastrointestinal side effects and nephrotoxicity most commonly seen. Prospective and sequential analysis of renal function provided strong evidence for cumulative nephrotoxicity in these patients given bolus injections of cis-dichlorodiammineplatinum(II) without prehydration or treatment with fuosemide or mannitol.

Phase II evaluation of cis-dichlorodiammineplatinum(II) in lymphomas: a Southwest Oncology Group Study.

The Southwest Oncology Group has evaluated the activity of cis-dichlorodiammineplatinum(II) at a dose of 75 mg/m2 given as an iv bolus injection every 3 weeks to 25 fully and partially evaluable patients with advanced Hodgkin's disease and non-Hodgkin's lymphoma. One complete response, two partial responses, and one improvement less than a partial response were noted. Myelosuppression, in the form of leukopenia and thrombocytopenia, was identified and seemed to be more prevalent and more severe than in previous studies. We have attributed this to the extensive prior treatments which these patients had received and to the presence of tumor-bearing marrow which was observed in some of them. The anticipated toxic effects which were noted included nausea and vomiting, anorexia, diarrhea, renal injury, and hyperuricemia. The precise role of cis-dichlorodiammineplatinum(II) in the management of human lymphomas awaits elucidation.

Phase I--II study of intermittent bolus administration of DTIC and actinomycin D in metastatic malignant melanoma.

Twenty-six patients with disseminated malignant melanoma were treated with intermittent bolus DTIC and actinomycin D in an escalating dose schedule, starting at 650 and 1 mg/m2 respectively. Courses were repeated at 3--4-week intervals. Twenty four patients were evaluable for toxicity and 22 were evaluable for response. Two patients (9%) had a complete remission lasting 7+ and 14 months, and three patients (14%) had a partial remission lasting 2+, 5+, and 14+ months. Nausea and vomiting, lasting 24 hours, was observed in 88% of patients, while diarrhea was noted in 17%. Stomatitis and alopecia were less frequently observed. All responses occurred at nonmyelosuppressive doses and in patients with visceral-predominant metastases. This schedule offers the patient the convenience of single-day treatment and less prolonged gastrointestinal intolerance. Further evaluation of this drug combination and schedule would appear to be indicated.

Aggressive versus conservative management of stage IV renal cell carcinoma.

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.

Diethylstilbestrol: recommended dosages for different categories of breast cancer patients. Report of the Cooperative Breast Cancer Group.

A total of 523 postmenopausal breast cancer patients with progressive disease were entered in a radomized, double-blind study of four dosages of diethylstibestrol (DES): 1.5, 15, 150, OR 1,500 MG/DAY. Higher dosages produced significantly (p less than .05) higher regression rates: 21% for the 1,500 mg dosage, 17% for the 150 mg dosage, 15% for the 15 mg dosage, and 10% for 1.5 mg dosage. Durations of regressions were similar regardless of the dosages used to induce them. Although the highest dosage produced the highest regression rate overall, selecting the best dosage or treatment of choice for each type of patient based on menopausal age and on dominant metastatic site would result in more regressions.