Bill L. Tranum

Combination chemotherapy (CMFVP) versus L-phenylalanine mustard (L-PAM) for operable breast cancer with positive axillary nodes. A southwest oncology group study

The Southwest Oncology Group in a prospective randomized study compared one year of adjuvant combination chemotherapy with continuous CMFVP to two years of intermittent L‐PAM in women with operable breast cancer with histologically positive axillary lymph nodes. In fully evaluable patients with a 42‐month median and 30‐month minimum follow‐up, treatment failures have occurred in 26% of 145 receiving CMFVP and 47% of 167 women given L‐PAM (P = 0.002). Disease‐free survival times were significantly longer with CMFVP than with L‐PAM in the following subgroups: premenopausal women (P = 0.002), postmenopausal women (P = 0.002), women with 1–3 involved axillary nodes (P = 0.003), and women with four or more involved axillary nodes (P = 0.002). CMFVP was effective in pre‐ and postmenopausal women. There is a significant difference in survival in favor of CMFVP compared to L‐PAM (P = 0.005). The life table estimates of survival at 42 months are 86% for women on the CMFVP treatment arm and 73% for women on the L‐PAM treatment arm. There was no correlation between the interval from mastectomy to onset of chemotherapy (between one and six weeks) and recurrence rates. Acute toxicity with both treatment arms was moderate and reversible. These results show that continuous CMFVP is superior to intermittent L‐PAM in decreasing recurrences and increasing survival in both pre‐ and postmenopausal women with operable breast cancer with histologically involved axillary nodes.

Immunological skin testing and interpretation: a plea for uniformity.

Immunological skin tests are one of the major methods used for the assessment of ones immune status. A review of the literature clearly reveals that there is no uniform method for the administration and interpretation of skin tests. Without uniformity, it is obvious that data are not comparable. Contradictory conclusions may be reached from the same skin test data, depending upon the method of interpretation used. Precedent, rather than rationale, has often determined the method of interpretation. There are studies which suggest that slight induration or erythema, often considered negative, are significant immunologic events. The various methods of skin test administration and interpretation are reviewed. Recommendations for application and interpretation are presented so that uniformity may exist.

Combined modality therapy for first recurrence of breast cancer. A Southwest Oncology Group Study

The Southwest Oncology Group has completed a study of 213 women with the first recurrence of breast cancer. Eligibility included a radical or modified radical mastectomy for cure and recurrence which had received no other form of therapy. Patients were started on tamoxifen (TAM) 20 mg daily (Phase I). Failures, or responders who subsequently failed, had an oophorectomy if the ovaries were intact, and TAM was continued (Phase II). During Phase III, eligible patients underwent an adrenalectomy, and lastly, in Phase IV, patients received chemotherapy. Responses to TAM were seen in 40% of 56 premenopausal patients, 46% of 95 postmenopausal women, and 44% of 62 patients without intact ovaries. Oophorectomy plus TAM gave responses only in premenopausal women who failed to respond on TAM or in postmenopausal patients who had a prior response to TAM. Adrenalectomy was successful in 7 of 21 patients. Chemotherapy resulted in 13% complete and 47% partial responses. Median overall survival was 108, 155, and 115 weeks, respectively, for the three patient groups. The authors believe that until results with chemotherapy improve significantly, hormonal therapy is the preferred first‐line management of recurrent breast cancer.

Combination chemotherapy and systemic irradiation consolidation for poor prognosis breast cancer.

Seventy patients with poor prognosis, metastatic breast cancer were treated with FUVAC induction chemotherapy (5‐fluorouracil, vinblastine, Adriamycin [doxorubicin] and cyclophosphamide). Consolidation therapy was given to 30 of 48 responders (63%), of whom 23 received sequential hemibody irradiation (HBI) at 8 cGy, corrected in the upper half for lung transmission. Seven received high dose cyclophosphamide and total body irradiation (TBI) with subsequent infusion of stored, cryopreserved autologous bone marrow. The response rate to induction therapy was 71% (complete [CR] in 21%). The median survival for all patients entered in this study is 12 months. With consolidation, one CR patient who received cyclophosphamide and TBI is disease free at 20+ months, off all treatment, while HBI did not produce longterm remissions. Of 17 partial (PR) patients, two of 12 improved to CR with HBI, and one of five improved with cyclophosphamide plus TBI, but all ultimately relapsed. The main toxicity of sequential HBI was myelosuppression, with prolonged thrombocytopenia in 13%; only one case of radiation pneumonitis occurred (3%). Cyclophosphamide and TBI produced temporary, reversible marrow aplasia without other major toxicity. We recommend further investigation of Cytoxan (Bristol Myers Oncology Division, Evansville, IN) and TBI for breast cancer patients in remission after chemotherapy.

Perfusion lung scan: an aid in detection of lymphangitic carcinomatosis

Lymphangitic carcinomatosis is usually a late manifestation of metastatic disease. The patient usually presents with cough or dyspnea, and the chest radiograph is often nondiagnostic. Two patients are presented who developed symptoms while on adjuvant chemotherapy. Both had abnormal perfusion lung scans. One had matching ventilation defects; the other a normal ventilation study. Biopsy revealed metastatic carcinoma; in one case tumor was seen in both the pulmonary lymphatics and arterioles; in the other, tumor was identified but the site could not be specified. The radionuclide lung scan is a technique which can speed diagnosis and institution of therapy in lymphangitic carcinomatosis.

The treatment of acute leukemia with continuous infusion L-Alanosine

SummaryL-Alanosine, an antitumor antibiotic was administered by members of the Southwest Oncology Group (SWOG) to 22 patients with resistant acute non-lymphocytic leukemia. The drug was administered by continuous infusion for five days at a starting dose of 125 mg/m2/day. Mucositis was dose-limiting in 15 patients and no marrow aplasia was attained. As administered, L-Alanosine is not an effective single agent in acute leukemia.

Aclacinomycin A in the treatment of multiple myeloma: A Southwest Oncology Group study

SummaryFifty-two patients with progressive resistant multiple myeloma were entered in this Southwest Oncology Group Phase II study, using weekly intravenous Aclacinomycin A. Of forty-three evaluable patients for response, there was one partial remission of 2 years duration and two sustained clinical improvements with 25% reduction in paraprotein. Major toxicity seen was severe myelosuppression and significant nausea and vomiting requiring dose reduction and delay of the scheduled treatment. Cardiac arrhythmia was seen in one patient. Chronic daily schedule or continuous IV infusion is recommended for future study.

m-AMSA and adenocarcinoma of the endometrium. A Southwest Oncology Group study.

SummaryTwenty-eight patients with advanced or recurrent adenocarcinoma of the endometrium were treated with m-AMSA. Twenty-four patients (86%) were treated at 30 mg/M2/d × 3d q 21 d and four patients were treated at 40 mg/M2/d × 3d q 21 d intravenously. Eighty-eight courses of m-AMSA were administered with a median of 2 courses per patient. One (5%) complete response occurred in 19 patients evaluable for response. Toxicity was well tolerated and generally mild. m-AMSA may be relatively inactive in the treatment of advanced adenocarcinoma of the endometrium; further studies, however, are required to determine its effectiveness in primary previously untreated disease.

Mitoxantrone, cisplatin, and methyl-glyoxal bis-guanylhydrazone chemotherapy for refractory malignant lymphoma: A Southwest Oncology Group phase II trial

SummaryA phase II trial of combination chemotherapy with mitoxantrone, cisplatin, and methyl-glyoxal bix-guanylhydrazone (MGBG) was conducted in 32 patients with unfavorable histology malignant lymphoma. All patients had relapsed after only one prior chemotherapy regimen (CHOP — 56%; mBACOD — 28%). There were three complete and eight partial responses (overall response rate — 34%) among 32 eligible patients. The median duration of remission was 6.0 months. Severe granulocytopenia was common, with 19/32 patients (63%) suffering life-threatening, and 1/32 (3%) suffering fatal, granulocytopenia.We conclude that mitoxantrone-cisplatin-MGBG has modest activity as salvage treatment in malignant lymphoma patients, but produces severe toxicity.

Phase II evaluation of rubidazone (NSC-164011) in advanced carcinoma of the breast

SummaryThe 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.