Frankie A. Holmes

PURPOSE: This randomized phase III trial compared the efficacy and safety of capecitabine with or without bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. PATIENTS AND METHODS: Patients were randomly assigned to receive capecitabine (2,500 mg/m2/d) twice daily on day 1 through 14 every 3 weeks, alone or in combination with bevacizumab (15 mg/kg) on day 1. The primary end point was progression-free survival (PFS), as determined by an independent review facility. RESULTS: From November 2000 to March 2002, 462 patients were enrolled. Treatment arms were balanced. No significant differences were found in the incidence of diarrhea, hand-foot syndrome, thromboembolic events, or serious bleeding episodes between treatment groups. Of other grade 3 or 4 adverse events, only hypertension requiring treatment (17.9% v 0.5%) was more frequent in patients receiving bevacizumab. Combination therapy significantly increased the response rates (19.8% v 9.1%; P = .001); however, this did not result in a longer PFS (4.86 v 4.17 months; hazard ratio = 0.98). Overall survival (15.1 v 14.5 months) and time to deterioration in quality of life as measured by the Functional Assessment Of Cancer Treatment--Breast were comparable in both treatment groups. CONCLUSION: Bevacizumab was well tolerated in this heavily pretreated patient population. Although the addition of bevacizumab to capecitabine produced a significant increase in response rates, this did not translate into improved PFS or overall survival.

Taxol, an antimicrotubule agent, has shown promise for efficacy in treatment of breast cancer, but severe hypersensitivity reactions led to cessation of many phase I clinical trials. Consequently, investigators and the National Cancer Institute recommended that phase I and II studies of this agent use 24-hour infusions and antiallergic medications. Using a premedication regimen effective in preventing hypersensitivity reactions, we have performed a phase II trial of taxol in patients with metastatic breast cancer. Taxol was administered to 25 patients at a dose of 250 mg/m2 by 24-hour infusion every 21 days. These patients had received only one prior chemotherapy regimen, either adjuvant to surgery or for metastatic disease; all but two had received doxorubicin. In 60% of the patients, the dominant site of disease was the viscera. All patients were assessable. In April 1991, at a median time on study of 9 months (range, 5-13+ months), the objective response rate was 56% (12% complete and 44% partial; 95% confidence interval, 35%-76%). Disease progressed in only 8% of the patients. The median number of courses of therapy was 11. Granulocytopenia was the dose-limiting toxic effect, but neutropenia with fever occurred in only 5% of 232 courses. A chronic glove-and-stocking neuropathy developed in most patients, but no allergic reactions occurred. We conclude that taxol is an active agent in the treatment of metastatic breast cancer and that it warrants continued study. Currently, we are conducting a phase I trial of taxol plus doxorubicin. Future trials should address the optimal effective dose, the optimal sequencing of combinations, mechanisms of drug resistance in tumors, and dose-limiting toxic effects (particularly cardiac toxic effects of taxol given as a single agent or in drug combinations).

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

PURPOSE: We previously reported that four cycles of docetaxel/cyclophosphamide (TC) produced superior disease-free survival (DFS) compared with four cycles of doxorubicin/cyclophosphamide (AC) in early breast cancer. Older women are under-represented in adjuvant chemotherapy trials. In our trial 16% of patients were > or = 65 years. We now report 7-year results for DFS and overall survival (OS) as well as the impact of age, hormone receptor status, and HER2 status on outcome and toxicity. PATIENTS AND METHODS: Patients were randomly assigned to receive either four cycles of standard-dose AC (60/600 mg/m(2); n = 510), or TC (75/600 mg/m(2); n = 506), administered by intravenous infusion every 3 weeks. RESULTS: The median age in women younger than 65, was 50 years (range, 27 to 64) and for women > or = 65 was 69 years (range, 65 to 77). Baseline characteristics in the two age subgroups were generally well matched, except that older women tended to have more lymph node involvement. At a median of 7 years follow-up, the difference in DFS between TC and AC was significant (81% TC v 75% AC; P = .033; hazard ratio [HR], 0.74; 95% CI 0.56 to 0.98) as was OS (87% TC v 82% AC; P = .032; HR, 0.69; 95% CI, 0.50 to 0.97). TC was superior in older patients as well as younger patients. There was no interaction of hormone-receptor status or HER-2 status and treatment. Older women experienced more febrile neutropenia with TC and more anemia with AC. CONCLUSION: With longer follow-up, four cycles of TC was superior to standard AC (DFS and OS) and was a tolerable regimen in both older and younger patients.