R S Walters

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: To determine the efficacy (objective response rate and duration of response and survival) and toxicity of docetaxel in patients with strictly defined anthracycline-resistant metastatic breast cancer (MBC). PATIENTS AND METHODS: Thirty-five patients with bidimensionally measurable MBC who had progressive disease while receiving anthracycline-containing chemotherapy were registered onto the phase II trial. Docetaxel was administered at a dose of 100 mg/m2 over 1 hour every 21 days. RESULTS: Thirty-four patients were assessable for disease response; 18 (53%; 95% confidence interval [CI], 35% to 70%) achieved a partial response. The median times to disease progression and survival duration were 7.5 and 13.5 months, respectively, for responding patients. The median overall survival duration was 9 months. Two hundred eight cycles (median, five) of docetaxel were administered. Neutropenia with less than 500 cells/microL developed in 31 of 35 patients; it was complicated by fever in 30 (14%) of 208 cycles and in 18 (51%) of 35 patients, including one treatment-related death. Fluid retention was seen in 15 (43%) of 35 patients, including pleural effusions in 11 patients (31%). Moderate skin toxicity, asthenia, and myalgia were observed in 16%, 58%, and 37% of cycles, respectively. CONCLUSION: Docetaxel has the highest reported antitumor activity in anthracycline-resistant MBC. High objective response rates were seen in patients with visceral-dominant involvement, multiple metastatic sites, or extensive previous therapy. Docetaxel is associated with severe but reversible neutropenia, asthenia, and cumulative dose-related fluid retention. Dexamethasone decreased the frequency and severity of skin toxicity and appeared to ameliorate fluid retention.

One hundred twelve patients who developed acute leukemia or a myelodysplastic syndrome (MDS) after chemotherapy or irradiation for another malignancy were reviewed. The median time from initial therapy to development of secondary leukemia or MDS was 71 months (range, 7 to 331 months). The initial malignancy was hematologic in 43%. An MDS presentation occurred in 57 patients (51%), 55% of whom subsequently transformed to acute leukemia. Chromosomal abnormalities were documented in marrow specimens from 70 of 89 patients with analyzable metaphases (79%; 69% of the total group). Compared with 34 patients with metachronous secondary leukemia without prior chemotherapy or irradiation, those with therapy-related leukemia exhibited a significantly higher frequency of abnormalities of chromosomes 5 and/or 7 (43% v 18%), and lower incidence of diploid karyotypes (18% v 50%). Chromosome 5 and/or 7 abnormalities were also significantly higher in patients previously treated with alkylating agents, procarbazine, and nitrosoureas (72% to 83%), compared with those who had received cyclophosphamide-based regimens (29%), other chemotherapies (14%), or irradiation alone (29%). The median overall survival from diagnosis of the secondary leukemia or MDS was 30 weeks. Survival was significantly shorter for patients with acute leukemia compared with MDS presentation (21 v 45 weeks); in the latter category, it was similar whether evolution to acute leukemia occurred or not. Of 72 patients treated with antileukemia therapy, 29% achieved complete remission (CR). A multivariate analysis of prognostic factors demonstrated the cytogenetic pattern to be the most important characteristic determining remission rate and survival. Other important prognostic features were the morphologic presentation (MDS v acute leukemia) for probability of achieving remission, and patient age and marrow blasts percentage for survival.

An analysis was conducted of clinical and laboratory variables associated with response to remission induction therapy and remission duration in 440 patients with acute myelogenous leukemia treated between 1975 and 1983. The complete remission rate was 259/440 (59%). Specific cytogenetic abnormalities such as t(8;21), t(15;17), and inv16 were found to be favorable for response to therapy and/or remission duration, whereas those with a normal (diploid) karyotype had an intermediate prognosis. All other karyotypic abnormalities were associated with lower response rates and short complete remission durations. The karyotypes were classified as favorable, intermediate, and unfavorable groups for response and remission duration after allowing for all the other observed clinical and laboratory values related to prognosis. The cytogenetic classification was prospectively validated in an independent test group of 130 patients treated between 1983 and 1986 and showed a consistent relationship to response and remission duration. Logistic regression and proportional hazard models developed from the initial 440 patients were prospectively evaluated in the test group of 130 patients. Clear stratifications of patients into good, intermediate, and poor risk groups were obtained in the prospective tests. The karyotype of the leukemia cells is an independent prognostic variable for response and remission duration in acute myelogenous leukemia.

The response to and survival following first salvage therapy regimens for 243 patients with acute myelogenous leukemia (AML) treated between 1974 and 1985 were evaluated. Eighty (33%) patients obtained a complete remission (CR), 24% died prior to achieving a response, and 43% were resistant on their first salvage regimen. The median survival was 18 weeks. Five percent overall and 16% of the CR patients are predicted to survive for more than 5 years. The factor most strongly associated with response and survival was the duration of the initial remission with 49 of 82 (60%) patients whose initial CR duration was at least 1 year in duration obtaining a second CR v 31 of 161 (19%) for patients with a shorter remission (P less than .01). Age, liver function, serum lactic dehydrogenase (LDH), karyotype, and the proportion of blasts plus promyelocytes present at the time of starting salvage therapy were strongly associated with probability of response and survival. Multivariate analysis was used to develop logistic regression and proportional hazard models to predict probability of response and survival, respectively. The major regimens used were conventional-dose cytarabine (ara-C) (combined with anthracyclines or amsacrine), high-dose ara-C, rubidazone, amsacrine (AMSA), other anthracyclines, and autologous or allogeneic transplant programs. After allowing for the prognostic factors in the models, specific treatment regimens were not strongly associated with prognosis.