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Biomedical subjects

H B Muss

Publications and source records attributed to H B Muss.

At least 37 records · Page 2Linked to original sources
PubMed1997

Breast cancer in older women.

More than 50% of breast cancers are diagnosed in women aged 65 years or older, a quickly growing segment of the population. Healthy older women should be offered state-of-the-art screening and treatment for breast cancer, including mammography, surgery, radiation therapy, and adjuvant therapy for early stage tumors. Clinical trials focusing on the role of adjuvant treatment in older women with breast cancer are of chief importance. The optimal treatment for older women with life-threatening, comorbid conditions may be primary treatment with tamoxifen or adjuvant therapy with tamoxifen alone after definitive surgery. Outside the clinical trials setting, metastatic disease should be treated similarly in all age groups.

Aged↗
PubMed1997

Hormonal therapy of breast cancer: state of the art.

Hormonal therapy has an established role in the treatment of women with metastatic breast cancer and also is now a major component of adjuvant systemic therapy for those with early-stage disease. Moreover, recent data suggest that hormonal agents may have a potential use in the prevention of breast cancer in high-risk groups. This article will provide a general overview of the current roles of hormonal therapy and describe future directions that show particular promise.

Antineoplastic Agents, Hormonal↗
PubMed1996

Combination chemotherapy with hydroxyurea, dacarbazine (DTIC), and etoposide in the treatment of uterine leiomyosarcoma: a Gynecologic Oncology Group study.

Advanced or recurrent uterine leiomyosarcomas have traditionally been resistant to most chemotherapeutic regimens. Preliminary reports suggested the combination of hydroxyurea, dacarbazine (DTIC), and etoposide (VP-16) was sufficiently effective to warrant larger trials. In a Phase II trial undertaken by the Gynecologic Oncology Group, 39 patients with advanced or recurrent leiomyosarcoma were treated with 2 g of hydroxyurea, 700 mg/m2 of DTIC, and 300 mg/m2 of VP-16 in divided doses every 4 weeks. Thirty-eight patients were evaluable for response. Two patients experienced complete responses and five had partial responses for a total objective response rate of 18.4% (95% confidence interval: 7.7-34.3%). In general, therapy was well tolerated with moderate toxicity. Six of the seven responders had disease outside the pelvis. The combination of hydroxyurea, DTIC, and VP-16 exhibits moderate activity against uterine leiomyosarcoma.

Adult↗
PubMed1996

Leucovorin and high-dose fluorouracil in metastatic prostate cancer. A phase II trial of the piedmont Oncology Association.

We performed a Phase II trial of oral leucovorin and high-dose fluorouracil (5FU) in hormone refractory patients with metastatic prostate cancer who had not had prior chemotherapy. 5FU was given as a 24-hour infusion at a dosage of 4 g/m2 and oral leucovorin at a dosage of 50 mg every 6 hours for four doses, starting with the infusion of 5FU. Fifteen patients were treated and three were not evaluable for response. There were no complete (CR) or partial responses (PR) in 12 evaluable patients (95% confidence interval for CR+PR of 0 to 26%). Three patients had stable disease and the remainder progressed. Toxicities were generally mild to moderate, but one patient died of sepsis while neutropenic. This dose and schedule of leucovorin and 5FU is not better than single-agent 5FU in patients with metastatic prostate cancer.

Aged↗
PubMed1996

Tamoxifen in postmenopausal women a safety perspective.

Tamoxifen is a synthetic antiestrogen with both agonist and antagonist properties. It is believed to act primarily through binding to estrogen receptors in breast cancer cells, acting as a competitive inhibitor of estrogen. Tamoxifen has a wide range of systemic effects, possibly acting on every estrogen target tissue in the body. Tamoxifen therapy is associated with a significant reduction in the risk of recurrence and death in postmenopausal women with early stage breast cancer. In addition, it has been shown to effectively suppress preclinical breast cancer, as evidenced by the decrease in second primary breast cancers in adjuvant trials. Tamoxifen is also the most widely used endocrine therapy for women with metastatic breast cancer. Tamoxifen, acting predominantly as an estrogen agonist in the liver, has generally favourable effects on serum lipids in postmenopausal women. In addition, tamoxifen has been shown to preserve bone mineral density and may even decrease the risk of osteoporosis in these women. Most patients treated with tamoxifen have minimal adverse effects. Vasomotor symptoms are the most commonly reported events. Less frequently, vaginal discharge or dryness, nausea and depression have been reported. A slight increase in thromboembolic events in postmenopausal women taking tamoxifen has been suggested in some adjuvant trials. Rarely, ocular toxicity and hepatotoxicity are found. The adverse effect of primary importance is the increased incidence of endometrial carcinoma. Several studies indicate that almost all of the tumours are of low histological grade and stage, similar to those seen with exogenous estrogen use. The relative risk of endometrial cancer in women taking tamoxifen is about 2 to 4 times higher than for postmenopausal women not taking tamoxifen. The benefits of tamoxifen outweigh the risks in almost all postmenopausal women with estrogen receptor-positive early stage breast cancer and in all women with metastatic breast cancer. Should tamoxifen prove to be an effective chemopreventive agent for breast cancer, the risks and benefits of treatment will have to be more carefully assessed for this setting.

Aged↗
PubMed1996

Combination cisplatin and carboplatin in advanced squamous cell carcinoma of the head and neck.

Twenty-three patients with advanced squamous cell carcinoma of the head and neck who had received no prior chemotherapy were treated with carboplatin 350 mg/m2 followed by cisplatin 50 mg/m2 every 28 days. Twenty-one of 23 patients were evaluable for response and toxicity. Eight patients (38%) achieved complete response (CR) or partial response (PR) with 2 CR and 6 PR. The overall median survival was 8.4 months (range 19 days-56+ months). The major toxicity was hematological with grade III/IV granulocytopenia in 32% and grade III/IV thrombocytopenia in 32%. There was very little nonhematological toxicity and no nephrotoxicity. There were no therapy-related deaths. The combination carboplatin/cisplatin is tolerable in patients with squamous cell carcinoma of the head and neck, with objective responses in 38%; however, the response rate was not superior to single-agent carboplatin or cisplatin. Further studies with a higher dose of cisplatin should be considered.

Adult↗
PubMed1996

Breast cancer in older women.

By the end of the 20th century, more than 50% of new breast cancer patients will be greater than 65 years old. Until recently, research focused on this older group of women has been minimal. Previous studies have indicated that the elderly are less likely to be screened, and have lesser and frequently inferior treatment. In contrast, the few clinical trials focusing on the elderly suggest that they do as well with surgery, radiation, and standard chemotherapy regimens as their younger counterparts. Comorbidity is, however, more common in older women, and must be factored into treatment and prognosis. The available data indicate that mammography should be used on a yearly to every-other-year basis for screening older women, including those older than 70 years and in fair to good health. Older women should offered breast preservation options and should receive breast radiation following lumpectomy. Tamoxifen may be used as initial therapy for frail women with early to late stage breast cancer, but is inferior to surgery in achieving long-term local control. Adjuvant tamoxifen should be considered for all high-risk node-negative and all node-positive patients regardless of receptor status. Adjuvant chemotherapy is reasonable for high-risk node-negative and node-positive patients in good health and with reasonable life expectancy (>5 years), although clinical trials have not established efficacy for women in this age group. Older women with metastatic breast cancer are good candidates for endocrine therapy. Chemotherapy should be offered to those with progressive disease after endocrine therapy. There are inadequate numbers of older women enrolled in breast cancer clinical trials. Both physicians and patients should explore and define the barriers to clinical trial participation and develop successful interventions to overcome them.

Adult↗
PubMed1996

Phase I study of N-(phosphonacetyl)-L-aspartate with fluorouracil and with or without dipyridamole in patients with advanced cancer.

We conducted a combined biochemical modulation trial of N-(phosphonacetyl)-L-aspartate (PALA), dipyridamole (DP), and fluorouracil (5-FU) in patients with cancer. Eighty-eight patients with advanced cancer were entered into this Phase I trial. During the first part of the study, four doses of PALA (125, 250, 500, and 1000 mg/m2, administered on day 1) were evaluated to determine the PALA dose with maximal suppression of aspartate transcarbamylase (ATCase) activity that was clinically tolerable. Patients were randomized to receive DP (or no DP), 50 mg/m2, p.o. every 6 h on days 1-6, and all patients received 5-FU, 400 mg/m2, by bolus administration on days 2-5. Prior to and during therapy, WBCs were collected and assayed for ATCase activity. After the maximally tolerated PALA dose with 400 mg/m2 5-FU +/- 50 mg/m2 DP was defined, the 5-FU dose was escalated using the same administration schedule of 5-FU, PALA, and DP. The dose of 5-FU was escalated by 25% in each of the DP cohorts until dose-limiting toxicity was reached. ATCase activity was inhibited in a dose-dependent manner with PALA doses of 125, 250, 500, and 1000 mg/m2, resulting in 0, 13, 17, and 49% inhibition of ATCase activity. Only at the higher PALA doses (i.e., 500 and 1000 mg/m2) was ATCase activity suppressed during days 2-5, but the activity returned to pretreatment levels by day 15. Based on the clinical tolerance and significant suppression of ATCase activity, a PALA dose of 500 mg/m2 was selected for the 5-FU dose escalation phase. At a 5-FU dose of 625 mg/m2, dose-limiting toxicity (leukopenia, stomatitis, and diarrhea) occurred in both DP cohorts. We recommend that for this monthly treatment schedule, 500 mg/m2 PALA and 500 mg/m2 5-FU, with or without 50 mg/m2 DP, be used in subsequent Phase II trials.

Adult↗
PubMed1995

A phase II trial of 5-fluorouracil and high-dose leucovorin in recurrent epithelial ovarian carcinoma. A Gynecologic Oncology Group Study.

In this series 49 patients with epithelial ovarian carcinoma previously treated with platinum-based chemotherapy received leucovorin 200 mg/m2 i.v. bolus followed by 5-fluorouracil at 370 mg/m2 i.v. bolus daily for 5 days every 4 weeks for the first two courses and subsequent courses were given every 5 weeks. Of this group, 47 patients were evaluable for toxicity and 44 for response. Of the patients evaluable for response, 15 were considered platinum-sensitive and 29 were platinum-refractory. The overall response rate was 6/44 (13.6%). There were two complete responders (4.5%) and four partial responders (9.1%). In the platinum-sensitive patients, there was one complete response, yielding a response rate of 6.6%, whereas in the platinum-refractory patients, there were four partial responses and one complete response for a response rate of 17.2%. Five responses were in the pelvis and there was one response at an extrapelvic site in the abdominal mesentery. The median number of courses delivered was three (range: 1-10). The major adverse effect was myelosuppression with 16/47 (34.0%) experiencing granulocytopenia < 1,000/mm3. The median white blood count nadir for the patients experiencing any leukopenia was 2,700 (range: 400-3,900/mm3). There was one episode of grade 3 thrombocytopenia. Grade 3 intestinal toxicity was seen in seven patients (14.9%). There were no treatment-related deaths. In this previously treated population, 5-fluorouracil with high-dose leucovorin exhibited activity of interest in the platinum-refractory population and warrants further investigation.

Adult↗
PubMed1995

Patient preferences for treatment of metastatic breast cancer: a study of women with early-stage breast cancer.

PURPOSE: The purpose of this study was to elicit preferences for the treatment of metastatic breast cancer in women with early-stage breast cancer who were given hypothetical treatment scenarios. We predicted that quality of life, demographic, and treatment variables would have an impact on patient preferences. PATIENTS AND METHODS: One hundred fifteen patients with stage 1-IIIA breast cancer were interviewed. All patients had either mastectomy or lumpectomy plus radiotherapy as primary treatment. Sixty-seven (58%) had prior adjuvant chemotherapy. Patients were given four clinical scenarios that described a woman with metastatic breast cancer who was stated to have a life expectancy of 18 months. Side effects of the treatment options were systematically varied from low (hormonal therapy) to life-threatening (high-dose experimental therapy) and were consistent with common clinical situations. Patients were asked to select which treatment, with its associated toxicity, they would accept and prefer for a 50% chance of specified increments in life expectancy, ie, 5 years, 18 months, 1 year, 6 months, 1 month, and 1 week. RESULTS: Quality of life at the time of interview, previous chemotherapy treatment, and degree of difficulty of previous treatments did not predict patient preferences. The greater the toxicity potential of the treatment, the less likely patients were to accept the treatment, although approximately 15% of patients would prefer high-risk treatment for as little as 1 month of added life expectancy. Between 34% and 82% of patients would prefer different therapies for a 6-month addition to life expectancy, whereas almost all patients would accept treatment for a 5-year increase in length of survival. Younger patients were more willing to assume the risks of treatment for a small increase in life expectancy. Of note, between 54% and 78% of patients would elect to start the different treatments even without symptoms related to metastatic disease. Moreover, 76% of patients would prefer standard treatment or an experimental agent to reduce symptoms or pain, even if such treatment did not prolong life. Additionally, only 10% of patients would allow randomization to a clinical trial comparing high-dose with standard chemotherapy. Participation in the study was not distressing to most patients. CONCLUSION: Patients showed clear preferences for specific treatments for metastatic disease when given hypothetical scenarios. There was a wide range of patient preferences for treatment based on risk-benefit assessment, but a substantial percentage of patients would accept the risk of major toxicity for minimal increase in overall survival.

Adult↗
PubMed1995

Current status of endocrine therapy for metastatic breast cancer.

Hormonal manipulation is currently the mainstay of palliative care for metastatic breast cancer because it is well tolerated and produces significant responses in approximately one-third of unselected patients. Tamoxifen, a nonsteroidal antiestrogen, is currently considered first-line therapy. Second-line agents include progestins and aromatase inhibitors. New agents, such as the "pure" antiestrogens and the gonadotropin-releasing hormone (GnRH) agonists, are being tested. Other approaches for affecting the hormonal milieu are also under investigation, including combinations of hormonal agents, hormonal agents plus biologics, and hormonal agents plus antiproliferative agents. This review will address the basis for endocrine therapy and possible mechanisms of hormonal resistance, currently available agents and newer ones on the horizon, and areas of future interest.

Antineoplastic Agents, Hormonal↗
PubMed1994

The role of chemotherapy and adjuvant therapy in the management of breast cancer in older women.

The management of breast cancer in older women is a major challenge. A meta-analysis of randomized trials of adjuvant therapy in early stage breast cancer has indicated that the use of the antiestrogen tamoxifen improves relapse-free and overall survival for postmenopausal women, including those older than age 70 years. Tamoxifen therapy is of greatest benefit in patients whose primary lesions are estrogen- and progesterone-receptor positive, but lesser yet still significant benefits are seen in receptor-negative patients. Adjuvant chemotherapy has only been minimally studied in older women, because earlier trials tended to exclude women older than age 70 years from protocol entry. Trials are needed to explore the role of adjuvant chemotherapy in older women, especially those older than age 70 years. Metastatic breast cancer is incurable. Standard endocrine and chemotherapy regimens may be of great palliative benefit but probably only have modest effects on prolonging survival; older women should be offered such treatment. Initiating treatment for metastases with endocrine therapy does not compromise survival, even when such therapy is given to women who have receptor-negative malignancy. Patients progressing on endocrine therapy or whose metastatic disease is life-threatening should be considered for chemotherapy. Older women in generally good health tolerate standard doses of chemotherapy as well as their younger counterparts. Future research in this setting should include clinical trials designed specifically for the elderly and should include quality-of-life assessment as a major end point.

Aged↗
PubMed1994

Racial differences in survival from breast cancer. Results of the National Cancer Institute Black/White Cancer Survival Study.

OBJECTIVE: To examine the ability of recognized prognostic factors for breast cancer to account for the observed poorer survival in blacks compared with their white counterparts. DESIGN AND PARTICIPANTS: Subjects included 1130 women (612 blacks and 518 whites) aged 20 to 79 years residing in metropolitan Atlanta, Ga, New Orleans, La, or San Francisco/Oakland, Calif, who were diagnosed with primary invasive breast cancer. Information on stage, tumor characteristics, treatment, comorbid conditions, and sociodemographic factors was obtained from personal interview, physician and hospital records, and a pathology review of biopsy and surgical specimens. MAIN OUTCOME MEASURE: Multivariable survival models were used to estimate the hazard ratio (relative risk of mortality) for blacks compared with whites, adjusting for various combinations of potential explanatory factors. RESULTS: After controlling for geographic site and age, the risk of dying was 2.2 times (95% confidence interval [CI], 1.8 to 2.8) greater for blacks than whites. Adjustment for stage reduced the risk from 2.2 to 1.7; further adjustment for sociodemographic variables had no effect. Treatment was not a contributing factor once stage and tumor pathology were in the model. After adjusting for stage, treatment, comorbid illness, and pathologic and sociodemographic variables, blacks continued to demonstrate a slightly increased, but not statistically significant, risk of death (hazard ratio = 1.3; 95% CI, 1.0 to 1.8). Results were similar for all-cause mortality and breast cancer-specific mortality. CONCLUSIONS: Approximately 75% of the racial difference in survival was explained by the prognostic factors studied. Sociodemographic variables appeared to act largely through racial differences in stage at diagnosis, which may be amenable to change through improved access to and use of screening for black women.

Adult↗
PubMed1994

c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer.

BACKGROUND: The role of molecular markers in predicting the response to treatment of breast cancer is poorly defined. The Cancer and Leukemia Group B (CALGB) conducted a randomized adjuvant-chemotherapy trial (CALGB 8541) comparing three doses (high, moderate, and low) of cyclophosphamide, doxorubicin, and fluorouracil in 1572 women with node-positive breast cancer. This study (CALGB 8869) was designed to determine whether the DNA index, the S-phase fraction, c-erbB-2 expression, or p53 accumulation could be used as a marker to identify a subgroup of patients more likely than others to benefit from high doses of chemotherapy. METHODS: Tissue blocks were obtained from 442 patients randomly selected from the larger CALGB trial. Paraffin sections from the primary lesions were analyzed for DNA content, S-phase fraction, c-erbB-2 expression, and p53 accumulation. RESULTS: Patients randomly assigned to the high-dose regimen of adjuvant chemotherapy had significantly longer disease-free and overall survival if their tumors had c-erbB-2 overexpression. No further information was gained by adding the data on S-phase fraction or p53 accumulation to the analysis. There was no clear evidence of a dose-response effect in patients with minimal or no c-erbB-2 expression. CONCLUSIONS: There is a significant dose-response effect of adjuvant chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil in patients with overexpression of c-erbB-2 but not in patients with no c-erbB-2 expression or minimal c-erbB-2 expression. Overexpression of c-erbB-2 may be a useful marker to identify the patients who are most likely to benefit from high doses of adjuvant chemotherapy.

Adult↗
PubMed1994

Vincristine with high-dose etoposide in advanced breast cancer: a phase II trial of the Piedmont Oncology Association.

Vincristine (VCR) and etoposide (VP-16) have been shown to be synergistic in a murine model, and this combination was studied in a phase II trial. Eligibility required measurable disease, a performance status of 0-2, a life expectancy of > or = 2 months, an interval of at least 3 weeks since the receipt of previous radiation therapy or chemotherapy and recovery from related toxicity, no prior treatment with VCR or VP-16, and no more than two prior chemotherapy regimens (only one for treatment of metastatic disease). Treatment consisted of 0.5 mg i.v. (bolus) VCR followed by 200 mg/m2 VP-16 given over 2 h. Both drugs were given daily for 3 consecutive days every 3 weeks (total dose: VCR, 1.5 mg; VP-16, 600 mg/m2). A total of 18 patients with metastatic breast cancer were accured; 14 had adjuvant chemotherapy and 8 had chemotherapy for advanced disease. As judged by International Union Against Cancer (UICC) criteria, one complete response (CR) and three partial responses (PR) were obtained, for a CR + PR rate of 22% (95% confidence interval, 6%-48%). All responders had soft-tissue involvement only. Six patients had stable disease and 8 showed progression. The median time to treatment failure was 3.5 months, and the median survival from study entry was 8.3 months. The major toxicity was myelosuppression, with 9 patients (50%) experiencing a total WBC of < 1,000/mm3. Grade 2-3 neurologic toxicity was noted in 6 patients (33%) and grade 3 nausea and vomiting was noted in 5 (28%). The combination of VCR and VP-16 is active in advanced breast cancer but is not convincingly superior to either of these agents used alone.

Adult↗
PubMed1994

Tamoxifen versus high-dose oral medroxyprogesterone acetate as initial endocrine therapy for patients with metastatic breast cancer: a Piedmont Oncology Association study.

PURPOSE: To determine in a prospective randomized trial whether high-dose orally administered medroxy-progesterone acetate (MPA) was superior to tamoxifen in patients with recurrent or metastatic breast cancer who had received no prior endocrine therapy in either the adjuvant or advanced setting. PATIENTS AND METHODS: Patients initially received either tamoxifen 20 mg/d orally or MPA 1 g/d orally. At the time of disease progression, patients were crossed over to the other regimen. Eligibility required patients to be age > or = 18 years, performance status 0 to 3, and estrogen receptor (ER)- or progesterone receptor (PR)-positive or unknown. RESULTS: One hundred eighty-two eligible patients were entered and 166 were assessable for response. Complete plus partial response rates for tamoxifen and MPA were 17% and 34%, respectively (P = .01). Patients with bone metastases had a significantly higher partial response rate with MPA compared with tamoxifen (33% v 13%). Median time to treatment failure was 5.5 months for tamoxifen and 6.3 months for MPA (P = .48). The median survival duration was 24 months for tamoxifen and 33 months for MPA (P = .09). Multivariate analysis showed that treatment significantly influenced response rate, but not time to treatment failure or survival. After treatment failure following MPA, six of 42 patients (14%) treated with tamoxifen responded, compared with six of 49 (12%) treated with MPA following tamoxifen. Both agents were associated with minimal toxicity, but 35% of patients on MPA gained more than 20 lb as opposed to only 2% on tamoxifen. CONCLUSION: In this trial, initial treatment with MPA of endocrine-naive metastatic breast cancer patients was associated with a significantly higher response rate but not with improvement in time to treatment failure or survival, when compared with initial treatment with tamoxifen. Further randomized trials in patients with bone metastases are warranted to determine if high-dose progestin therapy is superior to tamoxifen in these patients.

Administration, Oral↗
PubMed1994

Management of disseminated disease in the patient with bladder cancer.

Advanced transitional cell carcinoma of the bladder is a chemotherapy-sensitive neoplasm. Several single agents demonstrate substantial activity, and combination chemotherapy produces responses in the majority of patients treated. The benefits and toxicities associated with the most widely used combination regimens are discussed. Other topics reviewed include the use of colony-stimulating factor support for chemotherapy, adjunctive surgical therapy, and newer cytotoxic regimens.

Antineoplastic Agents↗