D. Frye

PURPOSE: To determine the long-term clinical course of patients with metastatic breast cancer (MBC) who achieved a complete remission with doxorubicin-alkylating agent-containing combination chemotherapy programs. PATIENTS AND METHODS: To assess the long-term prognosis of MBC, we reviewed our experience with 1,581 patients treated on consecutive doxorubicin and alkylating agent-containing front-line treatment protocols between 1973 and 1982. Treatment was administered for a maximum duration of 2 years. Characteristics of long-term survivors were evaluated, and hazard rates for progression were calculated. RESULTS: From this group, 263 (16.6%) achieved complete responses (CR) and 49 (3.1%) remained in CR for more than 5 years. After a median duration of 191 months, 26 patients remain in first CR, four patients died in CR at times ranging from 118 to 234 months, 18 patients died of breast cancer, and one is alive with metastatic disease. Compared with the overall CR and total patient populations, the long-term CR group had more premenopausal patients, a younger median age, a lower tumor burden, and better performance status. The hazard function shows a substantial drop in risk of progression after approximately 3 years from initiation of therapy. Ten long-term CR patients developed second primary cancers: breast (3), ovary (2), pancreas (1), endometrium (1), colon (1), head and neck (1), and lung (1). CONCLUSION: Most patients with MBC treated with systemic therapies have only temporary responses to treatment, but some patients continue in CR following initial treatment. These data show that a small percentage of patients achieve long-term remissions with standard chemotherapy regimens. Remission consolidation strategies are needed.

Journal Article Phase II Trial of Taxol, an Active Drug in the Treatment of Metastatic Breast Cancer Get access Frankie Ann Holmes, Frankie Ann Holmes * Section of Breast Medical Oncology, Department of Medical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston, Tex * Frankie Ann Holmes, M.D., The University of Texas M. D. Anderson Cancer Center-Box 95, 1515 Holcombe Blvd., Houston TX 77030. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ronald S. Walters, Ronald S. Walters Section of Breast Medical Oncology, Department of Medical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston, Tex Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard L. Theriault, Richard L. Theriault Section of Breast Medical Oncology, Department of Medical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston, Tex Search for other works by this author on: Oxford Academic PubMed Google Scholar Aman U. Buzdar, Aman U. Buzdar Section of Breast Medical Oncology, Department of Medical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston, Tex Search for other works by this author on: Oxford Academic PubMed Google Scholar Debra K. Frye, Debra K. Frye Section of Breast Medical Oncology, Department of Medical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston, Tex Search for other works by this author on: Oxford Academic PubMed Google Scholar Gabriel N. Hortobagyi, Gabriel N. Hortobagyi Section of Breast Medical Oncology, Department of Medical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston, Tex Search for other works by this author on: Oxford Academic PubMed Google Scholar Arthur D. Forman, Arthur D. Forman Division of Medicine, Department of Neuro Oncology, The University of Texas M. D. Anderson Cancer Center Search for other works by this author on: Oxford Academic PubMed Google Scholar Lesley K. Newton, Lesley K. Newton Division of Medicine, Department of Neuro Oncology, The University of Texas M. D. Anderson Cancer Center Search for other works by this author on: Oxford Academic PubMed Google Scholar Martin N. Raber Martin N. Raber Clinical Trials Administration, Department of Medical Oncology, The University of Texas M. D. Anderson Cancer Center Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 24, 18 December 1991, Pages 1797–1805, https://doi.org/10.1093/jnci/83.24.1797-a Published: 18 December 1991 Article history Received: 23 July 1991 Revision received: 03 October 1991 Accepted: 04 October 1991 Published: 18 December 1991

Two hundred and seventy-four consecutive patients with measurable metastatic breast cancer, without prior exposure to cytotoxic agents were treated with tamoxifen, 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC). The initial 133 patients received doxorubicin by bolus IV administration and for the next group of 141 patients doxorubicin was administered via a central venous catheter over a 48-hour (79 patients) or 96-hour (62 patients) continuous infusion schedule. Patients treated with bolus doxorubicin had this agent discontinued usually when 450 mg/m2 were reached; for patients in the infusion group treatment was continued until evidence of progressive disease or clinical or subclinical cardiac dysfunction developed. The complete remission rate was 21% the partial remission rate, 59%. There were no differences in response rate, response duration, or survival duration between groups of patients treated with doxorubicin by bolus, 48-hour or 96-hour infusion FAC. The incidence of moderate and severe nausea and vomiting was lower in the group of patients treated with infusion FAC as compared to bolus FAC (P less than 0.001); however, the incidence of mucositis was higher in the infusion group than in the bolus group (P less than 0.001). Doxorubicin administered by continuous infusion schedules was less cardiotoxic than when administered by bolus, as shown by a greater than 75% decrease in the frequency of clinical congestive heart failure at cumulative dosages greater than or equal to 450 mg/m2 (P = 0.004). Doxorubicin administered as a 48-hour or 96-hour continuous IV infusion is safer, and better tolerated than doxorubicin administered by bolus.

PURPOSE: Most of the data about high-dose chemotherapy (HDCT) for metastatic breast cancer are derived from phase II studies. The interpretation of these data depends on comparisons with data from properly selected historical control patients treated with standard therapy under similar circumstances. We report the long-term results of patients with metastatic breast cancer who were eligible for HDCT but were treated with doxorubicin-containing standard-dose chemotherapy. PATIENTS AND METHODS: Prospectively collected data from 18 successive doxorubicin-containing protocols for the treatment of metastatic breast cancer were evaluated. Using common eligibility criteria for HDCT, we identified patients who would have been candidates for HDCT. We analyzed response rates, progression-free survival (PFS), and overall survival (OS) for all patients, potential HDCT candidates, and noncandidates. RESULTS: A total of 1,581 patients was enrolled onto the 18 studies. Six hundred forty-five were HDCT candidates, and 936 were noncandidates. The complete response rate was 27% for HDCT candidates and 7% for noncandidates; median PFS was 16 and 8 months and median OS was 30 and 17 months, respectively. Survival rates for HDCT candidates and noncandidates, respectively, were 21% and 6% at 5 years and 7% and 2% at 10 years. CONCLUSION: This study suggests that encouraging results of single-arm trials of HDCT could partially be due to selection of patients with better prognoses and further stresses the importance of completing ongoing randomized trials of HDCT to assess the relative efficacy of HDCT in patients with metastatic breast cancer.

Fifty-nine evaluable patients under 65 years of age with measurable metastatic breast cancer and without prior chemotherapy were randomly assigned to treatment with fluorouracil, Adriamycin (Adria Laboratories, Columbus, OH), and cyclophosphamide (FAC) at standard or high doses (100% to 260% higher than standard FAC) following a dose escalation schedule. Patients randomized to the high-dose FAC received the first three cycles of therapy within a protected environment. Subsequent cycles for this group were administered at standard doses of FAC in an ambulatory setting, the same as for the control group. After reaching 450 mg/m2 of Adriamycin, patients in both groups continued treatment with cyclophosphamide, methotrexate, and fluorouracil until there was disease progression. Analysis of pretreatment patient characteristics showed an even distribution for most known pretreatment factors, although the control group had slightly (but nonsignificantly) more favorable prognostic characteristics. Fourteen patients (24%) achieved a complete remission (CR) and 32 (54%) achieved a partial remission (PR), for an overall major response rate of 78%. There were no differences in overall, CR, or PR rates between the high-dose FAC and control groups. The median response durations were 11 and 10 months for the protected environment and control groups, respectively, and the median survival was 20 months for both groups. Hematologic, gastrointestinal (GI), and infection-related complications were significantly more frequent and severe in the group treated with high-dose chemotherapy. Stomatitis, diarrhea, and skin toxicity were dose-limiting. However, there were no treatment-related deaths. High-dose induction combination chemotherapy with the agents used in this study failed to increase the response rate or survival duration, and resulted in a substantial increase in toxicity.