Immediate and long-term toxicity of adjuvant chemotherapy regimens containing doxorubicin in trials at M.D. Anderson Hospital and Tumor Institute.

Seven hundred and ninety-six consecutive patients with operable primary breast cancer treated with doxorubicin-containing postoperative adjuvant chemotherapy between 1974 and 1982 were evaluated for assessment of the acute and long-term toxicities of the program. Most patients experienced nausea, vomiting, and alopecia, side effects that were totally reversible. Doxorubicin skin infiltration was observed in 6% of the patients. Hematologic toxicity was moderate, and only 26% of the patients had a granulocyte nadir of less than 1000 cells/ml. Febrile or infectious complications occurred in 6% of patients, of which 3% required hospitalization for observation and antibiotic treatment. No long-term hematologic changes were observed. Amenorrhea was reported by 80% of premenopausal patients. However, none of the patients under 30 years of age had menstrual abnormalities, whereas 96% of those 40-49 years of age developed amenorrhea. Amenorrhea was permanent for most women over 40, but for 50% of patients under 40 years of age, it was reversible. Endocrinologic studies showed that amenorrhea was a result of primary ovarian failure. The incidence of second malignant neoplasms was lower (1.3%) in the group treated with 5-fluorouracil, doxorubicin, and cyclophosphamide than in the historical control group (4.8%). Cardiac toxicity data was evaluated in 460 patients. When up to a cumulative dose of 300 mg/m2 was given, 1% of the patients developed congestive heart failure. In 4 of these 5, adequate control was achieved with medical treatment; 1 patient died as a consequence of cardiac toxicity.

Results of adjuvant chemotherapy trials in breast cancer at M. D. Anderson Hospital and Tumor Institute.

Between 1974 and 1982, 796 patients with operable breast cancer following local therapy were treated with 3 consecutive doxorubicin-containing adjuvant therapy trials. The median follow-up of patients entered on the first trial was 102 months; the second trial, 71 months; and for the third trial, 41 months. The treatment program consisted of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC). We altered the study designs to determine the role of nonspecific immunotherapy with BCG and postoperative irradiation in the second trial and the impact of additional chemotherapy with alternate drugs after completion of FAC in the third trial. In the first study, an overall 39% reduction in mortality was observed, and, in stage II disease, reductions of 54% and 37% in mortality were observed for patients less than 50 and greater than or equal to 50 years of age, respectively, in comparison to the historical control group. The data of the second trial illustrated that BCG and postoperative irradiation had no significant impact on the disease-free and overall survival. In the third trial, patients with estrogen receptor-positive tumor treated with additional chemotherapy with alternate drugs following completion of FAC had significantly superior disease-free survival compared with patients who did not receive additional chemotherapy. The results of 3 studies show that intensive combination chemotherapy significantly reduced the risk of recurrence and death in patients with breast cancer.

Self-help groups for parents of young drug and alcohol abusers.

A national movement of parent self-help groups has recently emerged to combat drug abuse in children and adolescents. This innovative modality addresses a major mental health problem in an area where manpower shortages are anticipated. On the basis of self-report data from 135 parent group members, the drug and behavior problems of their children were evaluated. Improvement was reported in the community at large but more frequently in the children of members. The parent groups differed notably in structure and activities; nonetheless, the underlying psychology of membership, i.e., the shared attitudes and social cohesiveness of the members, facilitated the achieving of common goals.

Combined modality approach in breast cancer with isolated or multiple metastases.

One hundred thirty-six patients with isolated recurrence of breast cancer received regional therapy (surgery and/or irradiation) followed by combination chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide (FAC). The disease-free survival of the group receiving FAC was compared to that of a historical control group treated with only regional therapy. The median disease-free interval between the first and second recurrence for the control group was 9 months and for the patients receiving FAC, 38 months (p less than 0.01). The median survivals from first recurrence for the control and the FAC groups were 40 months and 60 months, respectively (p less than 0.02). In addition, 20 selected patients with multiple sites of metastasis or bulky isolated recurrence were initially treated with FAC chemotherapy; following complete or partial response with chemotherapy, these patients had regional therapy at the known sites of metastases. At a median follow-up time of 54 months, 9/20 patients (45%) have remained in complete remission. Combined modality approach significantly prolongs the disease-free survival of patients with isolated recurrences of breast cancer, and in selected patients with multiple metastases, this approach results in extended complete remissions.