Biomedical subjects

Hyman Muss

Publications and source records attributed to Hyman Muss.

7 recordsLinked to original sources

PubMed2006

Interleukin-6, multidrug resistance protein-1 expression and response to paclitaxel in women with metastatic breast cancer: results of cancer and leukemia group B trial 159806.

Several reports have suggested that breast cancer patients with elevated serum levels of interleukin-6 (IL-6) have a worse prognosis than patients with lower levels. We have studied IL-6 in breast cancer cell lines and have shown that autocrine production of IL-6 can confer multi-drug resistance in vitro by inducing multidrug resistance gene-1 transcription with subsequent overexpression of P-glycoprotein (PGP). Both IL-6 and PGP expression can be measured in malignant cells using immunohistochemical (IHC) techniques. We hypothesized that patients whose tumors expressed higher amounts of IL-6 or PGP would be less likely to respond to paclitaxel, an agent affected by the PGP pathway. If so, then IL-6 could serve as a predictive factor for paclitaxel sensitivity. Both IL-6 and PGP expression were measured in patients treated in a randomized trial that compared three doses of single agent paclitaxel (175, 210, and 250 mg/m(2) over 3 h every 3 weeks) in 469 women with metastatic breast cancer (CALGB 9342). No difference in complete and partial response was found among the three treatment arms. Tissue blocks in this trial were analyzed for IL-6 (154 patients) and PGP (149 patients) in paraffin-embedded sections from tumor samples; clinical characteristics of these patients were similar to the total sample of 469 patients. There were no significant differences among IL-6 or PGP scores whether measured as continuous or dichotomous variables, or by other scoring, and response to paclitaxel. In multivariate analysis neither IL-6 nor PGP was a significant predictor of time to progression or overall survival. IHC expression of IL-6 and PGP levels in tumor cells is not a predictive marker for response to paclitaxel in women with metastatic breast cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group Study.

PURPOSE: To compare whole-abdominal irradiation (WAI) and doxorubicin-cisplatin (AP) chemotherapy in women with stage III or IV endometrial carcinoma having a maximum of 2 cm of postoperative residual disease. PATIENTS AND METHODS: Four hundred twenty-two patients were entered onto this trial. Of 396 assessable patients, 202 were randomly allocated to receive WAI, and 194 were allocated to receive AP. Irradiation dosage was 30 Gy in 20 fractions, with a 15-Gy boost. Chemotherapy consisted of doxorubicin 60 mg/m2 and cisplatin 50 mg/m2 every 3 weeks for seven cycles, followed by one cycle of cisplatin. RESULTS: Most patient and tumor characteristics were well balanced. The median patient age was 63 years; 50% had endometrioid tumors. Median follow-up time was 74 months. The hazard ratio for progression adjusted for stage was 0.71 favoring AP (95% CI, 0.55 to 0.91; P < .01). At 60 months, 50% of patients receiving AP were predicted to be alive and disease free when adjusting for stage compared with 38% of patients receiving WAI. The stage-adjusted death hazard ratio was 0.68 (95% CI, 0.52 to 0.89; P < .01) favoring AP. Moreover, at 60 months and adjusting for stage, 55% of AP patients were predicted to be alive compared with 42% of WAI patients. Greater acute toxicity was seen with AP. Treatment probably contributed to the deaths of eight patients (4%) on the AP arm and five patients (2%) on the WAI arm. CONCLUSION: Chemotherapy with AP significantly improved progression-free and overall survival compared with WAI. Nevertheless, further advances in efficacy and reduction in toxicity are clearly needed.

Abdomen↗

PubMed2005

Developing a cancer-specific geriatric assessment: a feasibility study.

BACKGROUND: As the U.S. population ages, there is an emerging need to characterize the "functional age" of older patients with cancer to tailor treatment decisions and stratify outcomes based on factors other than chronologic age. The goals of the current study were to develop a brief, but comprehensive, primarily self-administered cancer-specific geriatric assessment measure and to determine its feasibility as measured by 1) the percentage of patients able to complete the measure on their own, 2) the length of time to complete, and 3) patient satisfaction with the measure. METHODS: The geriatric and oncology literature was reviewed to choose validated measures of geriatric assessment across the following domains: functional status, comorbidity, cognition, psychological status, social functioning and support, and nutritional status. Criteria applied to geriatric assessment measurements included reliability, validity, brevity, and ability to self-administer. The measure was administered to patients with breast carcinoma, lung carcinoma, colorectal carcinoma, or lymphoma who were fluent in English and receiving chemotherapy at Memorial Sloan-Kettering Cancer Center (New York, NY) or the University of Chicago (Chicago, IL). RESULTS: The instrument was completed by 43 patients (mean age, 74 yrs; range, 65-87 yrs). The majority had AJCC Stage IV disease (68%). The mean time to completion of the assessment was 27 minutes (range, 8-45 mins). Most patients were able to complete the self-administered portion of the assessment without assistance (78%) and were satisfied with the questionnaire length (90%). There was no association noted between age (P = 0.56) or educational level (P = 0.99) and the ability to complete the assessment without assistance. CONCLUSIONS: In this cohort, this brief but comprehensive geriatric assessment could be completed by the majority of patients without assistance. Prospective trials of its generalizability, reliability, and validity are justified.

Activities of Daily Living↗

PubMed2004

Effect of vitamin B12, folate, and dietary supplements on breast carcinoma chemotherapy--induced mucositis and neutropenia.

BACKGROUND: Although patients with malignant disease frequently use dietary supplements, the effects of these agents with regard to chemotherapy are unclear. Therefore, the authors investigated the influence of vitamin B12, folate, and nutritional supplements on chemotherapy-induced toxicity. METHODS: Women with breast carcinoma were asked to complete a questionnaire that recorded their use of dietary supplements. Blood samples were obtained for the assessment of serum vitamin B12 and folate levels before and after the first cycle of chemotherapy and for weekly complete blood counts. Toxicity was evaluated by measuring absolute neutrophil counts and the frequency and severity of oral mucositis. RESULTS: Of the 49 women who submitted questionnaires, 35 (71%) took a combined total of 165 supplements. Compared with patients in a previous study (performed in 1990), patients in the current study had dramatically increased serum folate levels. Initial neutrophil count, but not type of chemotherapy, patient age, or serum vitamin B12 level, was predictive of nadir absolute neutropenia and the decrease from initial neutrophil count to nadir (Nfall). After adjusting for initial neutrophil count, Nfall was found to be lower for women who were taking supplements compared with women who were not taking supplements (P = 0.01) and for women who were taking multivitamins (P = 0.01) or vitamin E (P = 0.03). Women with serum folic acid levels < 20 ng/mL had a smaller decrease in neutrophil count after chemotherapy than did women with higher folate levels (P = 0.04). No significant association between oral mucositis and initial neutrophil count, nadir neutrophil count, Nfall, age, vitamin B12 level, or folate level was found. CONCLUSIONS: The decrease in neutrophil count caused by chemotherapy was ameliorated by dietary supplementation with a multivitamin or vitamin E. In contrast, high serum folate levels were associated with the exacerbation of this decrease in neutrophil count.

Adult↗

PubMed2004

Failure of higher-dose paclitaxel to improve outcome in patients with metastatic breast cancer: cancer and leukemia group B trial 9342.

PURPOSE: Cancer and Leukemia Group B Protocol 9342 was initiated to determine the optimal dose of paclitaxel administered as a 3-hour infusion every 3 weeks to women with metastatic breast cancer. PATIENTS AND METHODS: Four hundred seventy-four women with metastatic breast cancer who had received one or no prior chemotherapy regimens were randomly assigned to one of three paclitaxel dosing regimens-175 mg/m(2), 210 mg/m(2), or 250 mg/m(2)-each administered as a 3-hour infusion every 3 weeks. Women completed self-administered quality of life and symptom assessment questionnaires at baseline and after three cycles of treatment. RESULTS: No evidence of a significant dose-response relationship was demonstrated over the dose range assessed. Response rates were 23%, 26%, and 21% for the three regimens, respectively. A marginally significant association (P =.04) was seen between dose and time to progression; however, in a multivariate analysis, the difference was even less apparent. No statistically significant difference was seen in survival. Neurotoxicity and hematologic toxicity were more severe on the higher dose arms. There was no significant difference in quality of life on the three arms. CONCLUSION: Higher doses of paclitaxel administered as a 3-hour infusion to women with metastatic breast cancer did not improve response rate, survival, or quality of life. There was a slight improvement in time to progression with higher dose therapy, which was offset by greater toxicity. When a 3-hour infusion of paclitaxel is administered every 3 weeks, 175 mg/m(2) should be considered the optimal dose.

Adult↗

PubMed2003

Phase II trial of antiepidermal growth factor receptor antibody C225 in patients with advanced renal cell carcinoma.

Fifty-five patients with metastatic renal cell carcinoma (RCC) were treated on a multicenter, single-arm Phase II trial. Patients received single-agent Cetuximab (C225) administered by intravenous infusion at a loading dose of 400 or 500 mg/m2 followed by weekly maintenance doses at 250 mg/m2. None of the patients treated with C225 achieved either a complete or partial response. The median time to progression was 57 days. The most frequently reported grade 3 or 4 toxicity treatment-related adverse events were acne (17%) and rash or dry skin (4%). The lack of clinical response or suggestion of prolonging time to progression compared to historical data with interferon-alfa supports no further study of single-agent C225 in patients with metastatic RCC.

Adult↗

PubMed2002

Survey of oncologists' perceptions of barriers to accrual of older patients with breast carcinoma to clinical trials.

BACKGROUND: Prior research has documented the under-representation in clinical trials of older patients with cancer. In part of a larger study to test the magnitude of these barriers to entering eligible older patients with carcinoma of the breast into clinical trials (Cancer and Leukemia Group B [CALGB] trial 9670), barriers to accruing eligible older patients to clinical trials were obtained from the physician's perspective. METHODS: One hundred fifty-six physicians (85% oncologists) who treated patients with breast carcinoma at 10 CALGB institutions completed a questionnaire concerning what they perceived as barriers to enrolling older patients with breast carcinoma on clinical trials and possible interventions that may improve accrual. RESULTS: Physicians' perceptions of the most important barriers to accrual of older patients were: 1) elderly patients have significant comorbid conditions that are not excluded by the protocol but that may affect how they would respond to treatment (16%); elderly patients have difficulty understanding what is required in a complicated treatment trial, resulting in poor compliance (16%); treatment toxicity (14%); and elderly patients often do not meet the eligibility criteria (15%). Oncologists most frequently suggested that the most effective interventions for improving the accrual of elderly patients to trials included making personnel available in the clinic to explain clinical trials to older patients and their families (25%) and providing physicians with educational materials concerning treatment toxicity in the elderly (18%). CONCLUSIONS: Physicians viewed barriers to accruing older patients with breast carcinoma to clinical trials as multidimensional, with the most important involving protocol requirements, treatment specific issues, and older patients' medical and cognitive characteristics. Thus, a variety of interventions would be needed to improve accrual of older patients to clinical trials, including increasing physicians' knowledge concerning treatment toxicity in the elderly, simplifying protocol requirements, and reducing treatment toxicity.

Adult↗