PubMed Health⌕ Search

Biomedical subjects

F A Dorr

Publications and source records attributed to F A Dorr.

32 records · Page 2Linked to original sources
PubMed1991

Potential role of tamoxifen in prevention of breast cancer.

Despite advances in early detection and treatment of breast cancer, primary prevention has not been well explored, especially for women at increased risk of disease due to reproductive factors and family history. There are, however, suggestions that primary prevention of breast cancer may be a realistic objective. Randomized clinical trials of adjuvant therapy for early-stage breast cancer have demonstrated a 35% decrease in contralateral breast cancers among women receiving tamoxifen compared with controls, suggesting a potential role for tamoxifen in chemoprevention of breast cancer in women at increased risk of the disease. Adjuvant therapy studies also demonstrate that tamoxifen is well tolerated by most patients and suggest additional health benefits from alterations in plasma lipid levels and stabilization of bone mineral loss in women receiving tamoxifen. Aspects of tamoxifen pharmacology, laboratory research, and clinical experience which support its investigation as a chemopreventive agent for breast cancer are summarized, and potential toxic effects are discussed.

Bone Density↗
PubMed1991

National Cancer Institute study of luteinizing hormone-releasing hormone plus flutamide versus luteinizing hormone-releasing hormone plus placebo.

A randomized, double-blind trial in patients with disseminated, previously untreated prostate cancer (stage D2) was designed to test the hypothesis that maximal androgen blockade improves the effectiveness of the treatment of prostatic cancer. Six hundred three men received leuprolide in combination with either placebo or flutamide, and were followed for a minimum of 5 years. The 303 patients randomly assigned to receive leuprolide and flutamide had a longer progression-free survival and an increase in the median length of survival compared with the 300 patients receiving leuprolide plus placebo. Differences between the treatments were particularly evident for men with minimal disease and good performance status.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Opportunities in clinical trials. Adjuvant breast cancer.

Breast cancer is the most common cancer in women in the US, with approximately two-thirds of patients presenting with tumors confined to the breast alone or breast and ipsilateral axillary lymph nodes. Although all of these women can be rendered free of detectable breast cancer by local therapeutic modalities, many will experience recurrences regionally or at distant sites. Nearly all patients who have distant recurrences will subsequently die of breast cancer. Although metastatic breast cancer responds to a variety of hormonal and chemotherapeutic interventions, it is rare that such therapy is curvative. Hence, there has been great interest in studying adjuvant systemic therapies. There is now a long clinical trial experience with adjuvant therapy in breast cancer that provides an extensive background for implementing recent advances in molecular and cellular biology in the clinical setting. Predictably, these laboratory-clinical correlations will provide important leads for future generations of randomized adjuvant trials, both by helping to target new therapies for particular subsets of patients and by identifying prognostic groups. In this report, current efforts in adjuvant therapy trials and laboratory-clinical correlations being conducted in conjunction with those trials are described.

Breast Neoplasms↗
PubMed1990

Leuprolide with and without flutamide in advanced prostate cancer.

In a randomized, double-blind trial for metastatic prostate cancer (Stage D2), 603 men received leuprolide, a gonadotropin-releasing hormone analog that inhibits the release of gonadotropins, coupled with either placebo or flutamide, a nonsteroidal antiandrogen that inhibits the binding of androgens to the cell nucleus. The 303 men receiving androgen blockade with leuprolide and flutamide demonstrated a longer progression-free survival (16.9 vs. 13.9 months, P = 0.039) and an increased median length of survival (35.0 vs. 27.9 months, P = 0.035). In the subgroup of men with minimal disease and good performance status, the advantages of maximal androgen blockade were more pronounced. It is concluded that combined androgen blockade with leuprolide and flutamide was more effective than leuprolide alone for patients with metastatic cancer of the prostate. The therapeutic benefits, although greatest in patients with minimum disease, need to be evaluated in a prospective, randomized fashion in trials specifically designed for men with minimal disease and good performance status. Exploratory analyses using the black race as an explanatory variable were also performed. Black race is associated with shorter survival times and is also associated with other prognostic factors, including recent weight loss, anemia, elevated phosphatase levels, and pain. These findings suggest the need for future studies of the relationship of black race and response to prostate cancer therapy.

Adult↗
PubMed1989

A controlled trial of leuprolide with and without flutamide in prostatic carcinoma.

To test the hypothesis that maximal androgen blockade improves the effectiveness of the treatment of prostatic cancer, we conducted a randomized, double-blind trial in patients with disseminated, previously untreated prostate cancer (stage D2). All 603 men received leuprolide, an analogue of gonadotropin-releasing hormone that inhibits the release of gonadotropins, in combination with either placebo or flutamide, a nonsteroidal antiandrogen that inhibits the binding of androgens to the cell nucleus. As compared with the 300 patients receiving leuprolide and placebo, the 303 patients randomly assigned to receive leuprolide and flutamide had a longer progression-free survival (16.5 vs. 13.9 months; P = 0.039) and an increase in the median length of survival (35.6 vs. 28.3 months; P = 0.035). The differences between the treatments were particularly evident for men with minimal disease and good performance status; however, further studies should be conducted in this subgroup. Symptomatic improvement was greatest during the first 12 weeks of the combined androgen blockade, when leuprolide alone often produces a painful flare in the disease. We conclude that in patients with advanced prostate cancer, treatment with leuprolide and flutamide is superior to treatment with leuprolide alone.

Aged↗
PubMed1989

Locally advanced breast cancer current status and future directions.

Patients described as having locally advanced breast cancer comprise a heterogeneous group of patients with variable clinical presentations. Systematic evaluation of patients with these presentations has been limited, with much of our current understanding based on retrospective reviews. Prospective pilot studies have demonstrated the feasibility of multimodality therapy. However, there have been few well-conducted randomized trials in this setting. Comparison of results among studies is made difficult by the varying eligibility criteria and the way in which the data are reported. The use of common and consistent definitions of operable and inoperable disease is necessary for a more uniform understanding of the therapeutic interventions necessary for a given patient within this broad category of Stage III or locally advanced breast cancer. There are a variety of opportunities for clinical research activities in this group of patients including tests of hormonal recruitment or synchronization, high dose chemotherapy requiring autologous bone marrow transplantation, perioperative or preoperative chemotherapy, and alternating chemotherapy with short course radiotherapy. The integration of clinical information with biological characteristics of the tumor such as cytokinetics, oncogene amplification, and hormone receptors will be an important and necessary focus of future investigation in this disease.

Breast Neoplasms↗
PubMed1988

Phase I clinical and pharmacokinetic investigation of didemnin B, a cyclic depsipeptide.

Didemnin B (NSC-325319), a cyclic depsipeptide isolated from a marine tunicate, has been evaluated in a Phase I trial. The drug was administered in a single intravenous infusion in 150 cm3 of normal saline every 30 min given every 28 days. Forty-three patients received 80 courses of the drug at doses ranging from 0.14 to 4.51 mg/m2. The dose-limiting toxicity was nausea and vomiting which began during or shortly after the infusion and was of variable duration. This toxicity was somewhat ameliorated by pretreatment with an aggressive antiemetic regimen. Mild hepatic toxicity also occurred with mild elevations of transaminases and bilirubin. One patient experienced an allergic reaction during his second infusion, characterized by chills, diaphoresis, flushing and hypotension. No objective anti-tumor response was seen during this trial. The recommended dose for Phase II studies on a single-dose schedule is 2.67 mg/m2 without prophylactic antiemetics and 3.47 mg/m2 if an antiemetic regimen is used. Preliminary pharmacokinetics suggest that didemnin B is sequestered or rapidly converted to a metabolite not identified by the antibody used in the radioimmunoassay. Further evaluation will be performed during Phase II studies.

Adult↗
PubMed1986

Phase I clinical investigation of 7-con-O-methylnogaril, a new anthracycline antibiotic.

7-con-O-Methylnogaril (menogaril, NSC-269148) is a new anthracycline antibiotic that has been evaluated in a Phase I clinical trial. The drug was administered in a single i.v. infusion over a period of 60 min given every 3 weeks. Twenty-four patients received 64 courses of the drug in a dose range of 16 to 256 mg/m2. Granulocytopenia was dose limiting and prolonged, requiring treatment delay in 5 of 9 patients treated at doses greater than or equal to 192 mg/m2. Concentration dependent phlebitis occurred in 12 patients, and was of minimal severity when the menogaril concentration was less than 1 mg/ml. Hair loss was experienced by 8 patients but was generally mild with only one patient developing total alopecia. Possible acute cardiac toxicity was noted in one patient who had a transient episode of atrial fibrillation following his fifth course of menogaril. Phase II studies of 7-con-O-methylnogaril are planned at a starting dose of 160 mg/m2 for patients with prior chemotherapy or radiotherapy, and 200 mg/m2 for those without prior therapy given at 28-day intervals.

Antineoplastic Agents↗
PubMed1986

Adjuvant therapy for breast cancer patients with negative lymph nodes.

Although approximately 50,000 cases of axillary node-negative breast cancer are diagnosed in the United States annually, the natural history of this heterogeneous disease is incompletely defined. Several series have reported 5-year relapse-free and overall survival ranging from 56% to 89% and 74% to 92%, respectively. Tumor necrosis and anaplastic morphology correlate with early treatment failure. The estrogen receptor and size of the primary tumor are probably also predictive of clinical course. Thus far, perioperative cyclophosphamide is the only systemic treatment demonstrated to prolong survival in a statistically significant fashion. Several ongoing studies are investigating the role of tamoxifen or cytotoxic chemotherapy, or both, in prospective randomized trials. However, too few patients with insufficient follow-up have been analyzed to permit definitive conclusions or recommendations.

Antineoplastic Agents↗
PubMed1985

Second cancers following antineoplastic therapy.

The occurrence of metachronous malignancies has long been a phenomenon of interest to physicians. The problem of treatment-related malignancies has added to that interest and has contributed to the understanding of carcinogenesis. Prolonged survival of patients with previously lethal diseases is now allowing the expression of long-term toxicities of the intensive therapies being used in many disease settings. Although the oncogenic potential of the various alkylating agents may not be equivalent, they have all been implicated as causing cancer in man. Procarbazine also appears to be highly carcinogenic in man. The intensity of treatment (duration and total dose) is a significant factor in the carcinogenesis of these agents. The dose-response relationship between radiation and cancer induction is less clear, but most believe that increasing radiation exposure increases the risk of cancer in a linear fashion. The combination of intensive chemotherapy and intensive radiotherapy yields the greatest risk for treatment-related hematologic and solid malignancies. To replace effective therapy with less carcinogenic therapy of unproved effectiveness would be difficult since survival curves have not been significantly affected by the evolution of treatment-related cancers. Whether that will hold true for the adjuvant use of intensive therapy remains to be seen. Where feasible, the design of such adjuvant trials should keep the dose-response relationship in mind. If the virtual absence of metachronous leukemia in Hodgkin's disease patients treated with ABVD holds true over time, the search for noncarcinogenic combination therapy will be well worth the effort. Therapeutic options in cancer treatment currently are few, and the benefits of potentially carcinogenic chemotherapy and radiotherapy continue to outweigh the risks.

Antineoplastic Agents↗
PubMed1985

Presence of an estrogen-regulated protein in endometrial cancer.

The presence of an estrogen-regulated protein of Mr 24,000 (24K) was studied in 43 patients diagnosed as having endometrial adenocarcinoma. using an anti-24K monoclonal antibody, a modified immunoperoxidase system (avidinbiotin complex) was used to detect the presence of 24K in formalin-fixed, paraffin-embedded tissue samples. The positivity for 24K was correlated with low tumor histologic grade, few mitotic figures, few nucleoli, and a low degree of nuclear pleomorphism. These data suggest that 24K may be a potential marker of tumor differentiation.

Adenocarcinoma↗