Chemotherapy of metastatic endometrial cancer.
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Biomedical subjects
Publications and source records attributed to H B Muss.
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BACKGROUND: Numerous studies have reported differences in cancer staging at diagnosis and in survival between Black and White patients with breast cancer. Utilizing data obtained from the National Cancer Institute's (NCI's) Black/White Cancer Survival Study for the period 1985-1986, a new study is presented here that systematically examines multiple explanatory factors (e.g., lack of mammograms) associated with these cancer-staging differences. PURPOSE: We evaluated within a single study the relationship of selected demographic, lifestyle, antecedent medical experiences, and health care access factors to cancer staging at diagnosis in Black and White breast cancer patients. METHODS: Data utilized in this population-based cohort study of 1222 eligible women (649 Black and 573 White) newly diagnosed for the period 1985-1986 with histologically confirmed primary breast cancer were obtained from the NCI's Black/White Cancer Survival Study. Sources of data included abstracts of hospital medical records, central review of histology slides by a study consultant pathologist, and patient interviews obtained from three metropolitan areas: Atlanta, New Orleans, and San Francisco-Oakland. Within each area, 70% of all Black incident cases were randomly selected, and a sample of White cases, frequency matched by age groups (20-49 years, 50-64 years, and 65-79 years), was selected for comparison. Stage of breast cancer at diagnosis was classified according to the international tumor-lymph node-metastases (TNM) system. Statistical models utilized in this study included the log-linear and polychotomous logistic regression with multiple predictor variables. RESULTS: Factors associated with cancer staging were differentially expressed in Blacks and Whites. Indicators of access to health care, a lack of mammograms, and an increased body mass index significantly (P < .02) contributed to stage differences in Blacks, whereas income was marginally associated (P = .06) with stage for Whites only. Nuclear grade, having a breast examination by a physician, and a history of patient delay explained approximately 50% of the excess risk for stage III-IV cancer versus stage I-IIN0 cancer among Blacks compared with Whites (odds ratio reduction from 2.19 to 1.68). CONCLUSION: These findings suggest that no single factor or group of factors can explain more than half of the race-stage differences noted in this study with respect to Black and White breast cancer patients.
Twenty-one evaluable patients with recurrent or metastatic endometrial carcinoma were treated with 1,500 micrograms/m2 of echinomycin every 3 weeks. All patients had received prior chemotherapy. There was one complete response (5%), 95% confidence interval for response is 0.9-22.7%. The major toxicity was nausea and vomiting which was moderate to severe in 42% of patients. Myelosuppression was minimal. Echinomycin, in this dose and schedule, displays minimal activity in patients with advanced endometrial carcinoma who have had prior chemotherapy.
BACKGROUND: The National Cancer Institute Black/White Cancer Survival Study began patient accrual in 1985 and was designed to investigate factors that might contribute to the observed racial differences in survival for cancer of the breast, uterine corpus, colon, and bladder. METHODS: To determine whether there were racial differences in treatment in a clinically homogeneous set of patients, 305 (25%) of the 1222 women in this study with Stage II node-positive (N+) breast cancer were evaluated. RESULTS: Patient characteristics for blacks and whites were similar for age, metropolitan area of residence, tumor size, extent of nodal involvement, and steroid receptors. Differences in histologic findings, tumor grade, and nuclear atypia were observed. Blacks had a higher frequency of comorbid conditions, especially hypertension (P < 0.00001). Fewer blacks underwent breast-conserving surgery (P = 0.004). In a multivariate analysis, race was no longer a significant factor in the selection of primary treatment, but education and metropolitan area of residence remained significant. Blacks and whites received similar postoperative systemic therapy, with combination chemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil) and tamoxifen, the most common cytotoxic and endocrine therapies used. CONCLUSIONS: The National Cancer Institute consensus statement concerning adjuvant therapy for breast cancer was published in the middle of the 2-year period that study cases were accrued, and treatment plans in this study generally agreed with consensus guidelines. Should survival differences in black and white patients with Stage II N+ disease in this study be found, they are unlikely to be attributable to differences in initial or postoperative treatment.
OBJECTIVE: To determine the effect of age on treatment outcome in women with metastatic breast cancer treated with chemotherapy. DESIGN: Case-comparison study of patients with metastic breast cancer treated in five clinical trials of the Piedmont Oncology Association. SETTING: University and private practice physicians participating in the Piedmont Oncology Association clinical trials in the southeastern United States. PATIENTS: Seventy patients 70 years of age or older were compared with 60 patients aged 50 through 69 years and 40 patients less than 50 years of age. All patients were ambulatory or capable of self-care, with adequate hematologic, renal, and hepatic function. INTERVENTIONS: Treatment with multidrug chemotherapy regimens. MAIN OUTCOME MEASURES: Response to treatment, time to disease progression, survival, and toxic effects. RESULTS: Pretreatment characteristics including race, performance status, disease-free interval, prior therapy, sites of metastatic disease, and number and dominant sites of metastases were similar for the three age groups. The response rates for the younger-than-50, 50-through-69, and 70-or-older age groups were 40%, 31%, and 29%, respectively (P = .53). There were no significant differences in time to disease progression or survival for patients in the three age groups. Estimates for time to progression and survival were 9.1 and 17.9 months, 6.2 and 12.8 months, and 7.2 and 14.2 months, respectively. Toxic effects, dose delivery, and dose delays were also similar for all three age groups. CONCLUSIONS: Women 70 years of age or older who were enrolled in these trials were similar to their younger counterparts in response rates, time to disease progression, survival, and toxic effects. Women in this age group should not be excluded, based on age alone, from clinical trials involving chemotherapy for advanced breast cancer.
Nineteen evaluable patients with recurrent or metastatic squamous cell carcinoma of the uterine cervix were treated with 1,500 micrograms/m2 of echinomycin every 4 weeks. No patient had received prior chemotherapy. There was one partial response (5% response, 95% confidence interval for response of 0% to 26%). The major toxicity was nausea and vomiting which was moderate to severe in six patients. Myelosuppression was not observed. Echinomycin, in this dose and schedule displays no major activity in chemotherapy-naive patients with advanced squamous-cell carcinoma of the cervix.
Fifteen patients with relapsed multiple myeloma (MM) were treated with menogaril 160 mg/m2 intravenously (IV) every 28 days. No responses were seen: 8 patients had stable disease, 4 progressed after one course of therapy, and 3 patients were removed from study after 1 course for other reasons. Four of the 8 patients with stable disease had an improved performance status, and 3 had a decrease in analgesic use. The major toxicity was myelosuppression. The median progression-free interval was 3.0 months with a range of 0.7 to 22 months and median survival was 11.3 months with a range of 0.7 to 39+ months. Menogaril displays little activity in patients with previously treated MM.
More than 45,000 women will die of metastatic breast cancer in the United States in 1991. Endocrine therapy remains a major option for treatment of such patients, and results in complete plus partial response rates of 30% with a median duration of approximately one year. Postmenopausal status, increased age, a prolonged disease-free interval, bone and soft tissue metastases, and positive estrogen and progesterone receptors are all associated with an increased response to endocrine therapy. The use of additive hormonal therapy, specifically antiestrogens, progestins, and aromatase inhibitors, have replaced surgical ablative procedures in the majority of patients; response rates to antiestrogen therapy, progestin therapy, and aromatase inhibitors are similar, but antiestrogens have generally been associated with the most favorable therapeutic index. At present, there is no convincing evidence that either combinations of endocrine therapies or endocrine therapy combined with chemotherapy are associated with an improvement in survival for patients with metastatic disease. Future research efforts directed at defining the molecular mechanisms of endocrine activity should facilitate clinical trials of newer and potentially more effective agents. All patients with metastatic breast cancer should be considered for at least one trial of endocrine therapy provided their metastatic disease is not rapidly progressive or life-threatening.
Progestin therapy has become an established endocrine modality for the treatment of metastatic breast cancer, with medroxyprogesterone acetate and megestrol acetate being the most widely used agents. Both drugs display similar effectiveness as initial and secondary therapy for patients with advanced disease, with combined complete and partial response rates of approximately 30% to 40%. Uncontrolled trials have suggested that high doses of medroxyprogesterone may be more effective than lower doses, but randomized trials have yielded conflicting results. Clinical trials of megestrol acetate have demonstrated it to be an affective, well-tolerated oral progestin, and a recent randomized trial has suggested that higher megestrol acetate doses may be associated with not only improved response but also improved time to disease progression and survival. Further trials of high-dose megestrol acetate for both initial and secondary therapy are under way, and their results will provide valuable information concerning the role of such treatment.
The Piedmont Oncology Association conducted a Phase II trial of fluoxymesterone (Halotestin) in 28 patients who failed to respond to prior hormonal therapy with tamoxifen and a progestational agent. Of nine patients who had responded to prior endocrine therapy, one had a partial response (PR) as defined by strict criteria and remains on study at 17 + months for an 11% response rate [95% confidence interval (CI), complete response (CR) + PR, 0-48%]. None of 19 previously unresponsive patients achieved remission (95% CI, CR + PR, 0-18%). Eleven patients' performance status deteriorated during therapy. Five of them had not received prior chemotherapy, and their response to subsequent chemotherapy may have been adversely affected. Third-line hormonal therapy with fluoxymesterone can be recommended only as a temporizing measure in patients with indolent disease who have responded to prior hormonal therapy.
Malignant pleural effusion is a common and significant source of morbidity for many patients with cancer. In an attempt to control this condition without using chest tube drainage, we administered recombinant interferon alpha-2b (INTRON, Schering-Plough, Kenilworth, NJ) intrapleurally via catheter after routine thoracentesis. Twenty-two installations of interferon were administered to 15 patients in incremental dosages of 3-50 x 10(6) U/m2. Of 20 evaluable treatments, six (30%) achieved effusion stabilization; there were no complete or partial responses. Only one of nine treatments at a dosage less than 20 x 10(6) units/m2 resulted in symptoms, while four of 11 treatments at the higher dosage were associated with transient fever, chills, and chest pain. Interferon demonstrated no major activity in this heavily treated patient population with advanced malignancy.
Eighteen evaluable patients with recurrent or metastatic nonsquamous carcinoma of the uterine cervix were treated with 1,500 micrograms/m2 of echinomycin every 4 weeks. Seven patients had received prior chemotherapy. There was one complete response (5.6%), 95% confidence interval for response of 0-27%. The major toxicity was nausea and vomiting, which was moderate to severe in eight patients. Myelosuppression was minimal. Echinomycin in this dose and schedule displays minimal activity in patients with advanced nonsquamous carcinoma of the cervix.
Twenty-one patients with recurrent epithelial ovarian carcinoma not amenable to cure with further surgery or radiotherapy were entered into a Phase II trial utilizing i.v. leucovorin at 20 mg/m2 followed by i.v. 5-fluorouracil at 425 mg/m2 administered daily for 5 days every 4 weeks for the first two courses and then every 5 weeks. Twenty-one patients were entered. Of these, 20 were eligible for toxicity assessment and 19 for response. Five had received prior radiotherapy, and all had received prior cisplatin-based chemotherapy. There was one patient response (5.3%; 95% confidence intervals for response of 0% to 26%). Toxicity was moderate with 5 of 20 (25%) grade 3 or 4 leukopenia, 12 of 20 (60%) grade 3 or 4 granulocytopenia, 1 of 20 (5%) grade 3 thrombocytopenia, 5 of 20 (25%) grade 3 GI toxicity, and 2 of 20 (10%) grade 3 neurotoxicity. There was one toxic death in a patient who developed granulocytopenia and pneumonia after her third course of treatment. This dose schedule of 5-fluorouracil and leucovorin has minimal activity in patients with recurrent epithelial ovarian carcinoma who have received prior cisplatin chemotherapy.
Twenty-eight patients with recurrent squamous carcinoma of the cervix not amenable to cure by further surgery or radiation therapy were entered into a Phase II trial utilizing i.v. leucovorin 20 mg/m2 followed by 5-fluorouracil 425 mg/m2 administered daily for 5 days every 4 weeks for the first two courses and then every 5 weeks. One patient never received therapy, and three are inevaluable for response; therefore, 27 patients were evaluable for toxicity and 24 for response. Twenty-three patients had received prior radiotherapy, and 16 had received prior chemotherapy. There was one partial response 4.2% (95% confidence intervals for a response of 0 to 21%). Although toxicity was acceptable with 11 of 27 (41%) grade 3 or 4 leukopenia, 1 of 27 (4%) grade 3 thrombocytopenia, and 3 of 27 (11%) grade 3 or 4 gastrointestinal toxicity, this dose schedule of 5-fluorouracil and leucovorin has minimal activity in recurrent squamous carcinoma of the cervix.
High-dose megestrol acetate (800 mg/day) was administered to 34 patients as third-line endocrine therapy for metastatic breast cancer after progression on standard-dose megestrol acetate (160 mg/day). Among the 32 evaluable patients, no complete or partial response occurred. Ten patients remained stable and 22 progressed. No patients remained on study. Median time to progression was 2 months (range, 1-13 months). The use of high-dose megestrol acetate did not result in objective responses but may have been effective in delaying progression in one third of patients.
BACKGROUND: Chemotherapy for metastatic breast cancer is palliative, and the optimal duration of therapy is unknown. We designed a trial to determine whether continuous treatment is superior to stopping treatment after a brief induction period and resuming treatment when the disease progresses. METHODS: We treated 250 women with metastatic breast cancer with six courses of cyclophosphamide, doxorubicin, and fluorouracil given every three weeks. At the completion of this induction period, women whose disease either regressed or remained stable were randomly assigned to receive either continued treatment with cyclophosphamide, methotrexate, and fluorouracil (maintenance therapy) or no further treatment (observation) followed by treatment with cyclophosphamide, methotrexate, and fluorouracil when disease progression became evident (reinduction). RESULTS: The combined rate of complete and partial responses after initial therapy was 30 percent (71 of 233 patients who could be evaluated; 95 percent confidence interval, 25 percent to 37 percent). In another 42 percent (98 patients), the disease remained stable. A total of 145 patients were randomized. Seventy-one were randomly assigned to the maintenance-therapy group, and 74 to the observation group. The median time to progression was 9.4 months for patients in the maintenance-therapy group and 3.2 months for patients in the observation group (P less than 0.001). After reinduction therapy, the median time to progression was 3.5 months. The median length of survival from the time of initial therapy was 14.8 months for all 250 patients; it was 21.1 months for the 71 patients in the maintenance-therapy group and 19.6 months for the 74 patients in the observation group (P = 0.67). Maintenance therapy was the most important determinant of the time before progression (P less than 0.001), but it was not associated with prolonged survival. The changes in performance status were similar in the patients in both groups, but nausea, vomiting, and mucositis were significantly more frequent in the maintenance-therapy group. CONCLUSIONS: In patients with breast cancer who received induction chemotherapy for 18 weeks, subsequent continuous chemotherapy was associated with a significant prolongation of the time before progression as compared with those receiving no further therapy; overall survival, however, was not significantly different in the two groups.
The authors report a case, perhaps the first, of immunoglobulin D (IgD) benign monoclonal gammopathy. The patient, a 48-year-old black woman, initially had a 500 mg/dl IgD-lambda M-spike, hypercalcemia, and anemia. There was no bone pain, lytic bone lesions, or evidence of renal failure. The bone marrow showed 2.8% plasma cells with a diffuse (not nodular) IgD plasmacytosis and strong lambda predominance. Only trace amounts of free lambda light chains could be demonstrated by immunoelectrophoresis in serum and concentrated urine. The anemia responded quickly to iron therapy. Chemotherapy was not initiated. Over the 6+ years of follow-up, the patient has had no progression of clinical disease attributable to her IgD monoclonal gammopathy. The IgD M-spike has steadily decreased.
Prior studies have shown that black patients with breast cancer have poorer survival times compared with white patients even when adjusted for stage. Seventy-four black patients treated on six Piedmont Oncology Association (POA) protocols were compared with 74 randomly selected white patients treated with the same protocols to determine if race had any independent effect on response, time to progression, or survival time. Patients were evenly matched for pretreatment characteristics with the exception that white patients had a significantly higher percentage of bone metastases and significantly less skin involvement. Response rates and median time to progression were similar for black patients and white patients at 31% and 25%, and 9.3 and 9.1 months, respectively. Black patients had poorer survival times even when adjusting for covariables; median survival time was 14.3 months for black patients and 20.3 months for white patients (P less than 0.05). The reason for this survival difference in Stage IV patients is unclear, but is unlikely to be related to treatment. Additional research in this area will be necessary to resolve this issue.