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Biomedical subjects

J Aisner

Publications and source records attributed to J Aisner.

At least 73 records · Page 4Linked to original sources
PubMed1990

Current status of high-dose progestins in breast cancer.

Progestins at standard doses have compared favorably with tamoxifen for the front-line treatment of women with metastatic breast cancer. Attempts to further enhance the role of progestins have centered on dosage escalation, based on European data suggesting a dose-response effect. A phase I/II pilot trial at the University of Maryland demonstrated that doses of megestrol acetate up to 1,600 mg/d were well tolerated for prolonged periods. Responses were seen in patients whose disease was refractory to both standard doses of megestrol acetate and to tamoxifen. Different mechanisms of progestin action on breast tumors are theorized at the higher doses, which could account for the dose-response effect. Two large multi-institutional dose comparison trials of megestrol acetate in metastatic breast cancer have been undertaken in the United States. The Piedmont Oncology Association recently reported a significant benefit for megestrol acetate 800 mg/d compared with the standard 160 mg/d in terms of response and disease-free and overall survival. The largest trial is currently ongoing in the Cancer and Leukemia Group B. They are comparing 800 and 1,600 mg/d with standard doses, and results from this study are eagerly anticipated.

Antineoplastic Agents↗
PubMed1990

Appetite stimulation and weight gain with megestrol acetate.

The extreme anorexia and cachexia associated with cancer and other disease states often have important physical and psychologic impact on both patients and their families. Weight gain resulting from megestrol acetate therapy in breast cancer patients suggests that progestins may be useful for alleviation of disease-associated appetite and weight loss. Early breast cancer experience, as well as preliminary data from a randomized, placebo-controlled trial of high-dose megestrol acetate in cancer anorexia and wasting, is therefore reviewed. Although the precise mechanism by which megestrol acetate exerts its effect remains unclear, weight gain was observed in 75% of patients in the high-dose study and in nearly all of those who remained on therapy for 6 weeks. It was concluded that, although megestrol acetate cannot be expected to directly affect the prognosis of patients with hormone-insensitive tumors, it may increase host resistance by improving nutritional status and/or enhancing the quality of life.

Adult↗
PubMed1989

Granulocyte transfusion therapy and amphotericin B: adverse reactions?

One hundred twenty-five granulocyte transfusions were given concurrently with amphotericin B to 31 granulocytopenic patients with acute leukemia during a four year period. Twenty-six patients had culture-documented, and 5 had presumed fungal infections; pulmonary infiltrates were present in 26 patient courses. Eight patients developed pulmonary deterioration temporally related to therapy with amphotericin, granulocyte transfusions, or both. One event occurred following amphotericin alone. Three additional reactions occurred in alloimmunized patients with antibodies to human leukocyte antigens (HLA) who received random donor granulocytes, which may indicate a potential mechanism for the pulmonary reactions. Two reactions potentially represent an adverse interaction between amphotericin and granulocytes, but these were reversible and were not unlike reactions expected with each modality alone. Our data fail to document a specific detrimental interaction between granulocyte transfusions and amphotericin beyond the reactions associated with each modality, and the data suggest that other clinical factors, particularly infection and alloimmunization, also contribute to pulmonary decompensation. We nevertheless recommend great care and attention be given to administering these modalities in the setting of severely ill patients.

Adolescent↗
PubMed1989

Current staging of lung cancer: an overview of current and newer approaches.

The purpose of this chapter is to update some of the current approaches to the pretreatment assessment of patients with lung cancer. We will place emphasis on both standard staging and newer techniques. Because of their clinical relevancy, small-cell (SCLC) and non-small-cell (NSCLC) lung cancers have been divided to emphasize the special needs and approaches to each.

Carcinoma, Non-Small-Cell Lung↗
PubMed1989

Nutritional concerns in cancer patients.

One of the prime nutritional concerns in cancer patients is cachexia and deteriorating nutritional status. Cachexia can occur as a result of either treatment or the tumor itself. The progressive malnutrition ultimately affects performance status and organ function. Tolerance to treatment may thus be decreased, which, in turn, may adversely affect toxicity and response. In addition, the deleterious effects of malnutrition on the immune system can increase susceptibility to infection. The weakness and fatigue related to muscle wasting and changes in metabolism affect physical appearance, leading to a loss of self-esteem. Thus, the vicious cycle of cachexia severely impacts on every aspect of daily life. Providing nutritional support and effective treatment may reverse the cachexia. Studies involving caloric supplements alone have not been encouraging. Conversely, studies using megestrol acetate have shown that cancer patients gain weight and that their sense of well-being improves. However, the mechanisms of weight gain remain unknown, and further studies are needed to determine the mechanisms by which appetite is stimulated or catabolism is inhibited or both. Nursing interventions to stimulate appetite and promote greater food intake, coupled with the use of agents that alter metabolism, such as megestrol acetate, may reverse the trend of cachexia and thus provide an increased sense of well-being and improved quality of life.

Antineoplastic Agents↗
PubMed1989

Phase II trial of N-methylformamide in advanced renal cancer.

N-methylformamide (NMF) (800-1,000 mg/m2 i.v. day 1) was given to 14 patients with measurable, advanced renal cell carcinoma in this Phase II trial. Treatment was repeated every 28 days. Significant toxicities included drug-induced hepatitis along with moderate nausea and vomiting. No objective responses were seen although several patients had stable disease with treatment for prolonged periods. NMF is not an active agent in renal cell cancer when administered by this schedule.

Adult↗
PubMed1989

Tumor volume and treatment outcome in small cell lung carcinoma.

The volume of some tumors correlates with local disease control, response, and survival. Small cell lung carcinoma presents with variable and often large intrathoracic masses. We assessed volume by two methods (summation of cross-sectional areas and Simpson's rule for estimating volume) and correlated volume with treatment outcome. Twenty-nine patients with small cell lung carcinoma (12 limited disease and 17 extensive disease) were analyzed for volume outcome correlations. There were five early deaths. Twenty-four had response correlations (11 limited disease and 13 extensive disease). Eighteen of the twenty-four achieved complete response. There was no apparent correlation between complete and/or partial response and pretreatment tumor volume. There was no apparent correlation between survival and volume. The methods of volume assessment correlate well with each other (r = 0.88) and either can be used with accuracy. So far there is also no correlation between chest tumor volume and intrathoracic recurrence. Our projections suggest that there is a low probability of correlating chest tumor volume and either response or survival. This is in keeping with the disseminated nature of the tumor which is its limiting factor in survival.

Carcinoma, Small Cell↗
PubMed1989

A novel pharmacodynamically based approach to dose optimization of carboplatin when used in combination with etoposide.

Thrombocytopenia, the dose-limiting toxicity of carboplatin, is manageable and predictable with the dosing equation: Dose (mg/m2) = (0.091) (creatinine clearance)/(body surface area) (desired percentage change in platelet count) + 86. We used this equation to dose patients receiving carboplatin (day 1) and etoposide (80 mg/m2 days 1 to 3). An initial cohort of 14 patients with non-small-cell lung cancer (NSCLC) were treated with 75% of the calculated dose of carboplatin (29 evaluable courses) as a precaution against added myelosuppression from combination chemotherapy. The observed reduction in platelets was essentially equal to the reduction in platelets predicted if patients had received carboplatin alone. Subsequently, a second cohort of 20 evaluable patients with NSCLC received the full calculated dose of carboplatin and etoposide (51 evaluable courses). There was a linear relationship between observed (o) and predicted (p) reductions in platelets. With full-dose carboplatin in combination with etoposide, there was a significantly greater carboplatin dosage administered, greater reduction in platelets, and lower platelet nadir. Among 34 evaluable patients (80 courses) there was one complete response (CR) and four partial responses (PRs) for an overall response rate of 15% (90% confidence +/- 9%). The median duration of survival for responders was 336+ days and for nonresponders was 204+ days. Therapy was well tolerated. This study, in addition, supports our concept of individualized dosing of carboplatin and the underlying pharmacokinetic/pharmacodynamic relationships and represents an interesting pharmacodynamic and quantitative approach to studying potential drug-drug interactions and defining appropriate dosages for combination chemotherapy.

Antineoplastic Agents↗
PubMed1989

Response to mesna, doxorubicin, ifosfamide, and dacarbazine in 108 patients with metastatic or unresectable sarcoma and no prior chemotherapy.

In this phase II trial, 105 eligible patients with no prior chemotherapy and advanced sarcoma received doxorubicin, ifosfamide, and dacarbazine (DTIC) with mesna uroprotection (MAID). Starting doses of these drugs were 60, 7,500, and 900 mg/m2 divided over 72 hours by continuous infusion, respectively. Mesna was given for 84 to 96 hours at 2,500 mg/m2/d. Myelosuppression was dose limiting, causing the only toxic death (sepsis). Nonhematologic toxicity consisted predominantly of anorexia and vomiting. Severe mucositis, macroscopic hematuria, renal tubular acidosis, renal failure, and CNS toxicity occurred in less than 5% of cycles. No cardiotoxicity was detected. The overall response rate (10% complete response [CR]) was 47% (95% confidence intervals, 5% to 18% and 37% to 57%, respectively). Most responses (approximately 70%) were observed within two cycles. Median times to progression were 10 and 9 months, respectively. Histologic high tumor grade, lesions less than 5 cm, and less than 1 year from diagnosis to study entry correlated with the probability of response. The median survival was 16 months. Time from diagnosis to study entry, performance status, and extent of disease, but not histologic grade, correlated with survival. Following CR, two patients remain disease-free at 32 and 16 months. Of the 15 additional patients rendered disease-free with surgery, two remain disease-free at 30 and 18 months with no further therapy. While most relapses occurred in sites of prior involvement, death from CNS metastases occurred in 11 of the 80 patients with high-grade sarcomas, of whom seven were still responding systematically (three complete responders). Because of its substantial response in this phase II trial, the MAID regimen is being compared with doxorubicin and DTIC alone in advanced sarcomas and to observation in the adjuvant treatment of high-grade sarcomas in randomized trials.

Actuarial Analysis↗
PubMed1989

A comparison of carboplatin plus methotrexate versus methotrexate alone in patients with recurrent and metastatic head and neck cancer.

Patients with recurrent and metastatic squamous cell carcinoma of the head and neck (SCCHN) were stratified by performance status, extent of disease, and prior radiotherapy and subsequently randomized to receive carboplatin (CBDCA; Bristol-Myers, Wallingford, CT) administered intravenously (IV) monthly, initially at doses of 400 mg/m2 in combination with methotrexate (MTX) given IV weekly at doses of 40 mg/m2 or MTX alone at the same dose/schedule. Significant dose-limiting myelosuppression required CBDCA dose reductions to 300 mg/m2 and, subsequently, 200 mg/m2. Nonhematological toxicities were not significant. Our study objective was to determine whether CBDCA plus MTX produce a substantial improvement in response rate over single-agent MTX. A response rate of 50% (complete [CR] plus partial response [PR]) for CBDCA plus MTX compared with 25% for MTX was specified as the difference to be detected. We employed a two-stage study design for randomized trials that allowed for early termination of studies involving relatively ineffective treatment regimens. With this design, the study could be closed after the first stage (20 patients entered onto each treatment arm) if the number of responders to CBDCA plus MTX were not superior to MTX. Five of 20 patients responded to treatment in each arm, and we were able to conclude that the addition of CBDCA to MTX is unlikely to result in a twofold increase in response rate compared with MTX alone in this group of patients. This two-stage design represents a simple and efficient method of testing the relative efficacy of new combinations containing at least one active agent against a suitable control arm in this disease. It addresses scientific and ethical issues of continuing testing with relatively ineffective treatments, and at the same time provides a reliable method for identifying very active regimens likely to represent significant therapeutic advances.

Adult↗
PubMed1989

Tamoxifen withdrawal response. Report of a case.

A postmenopausal patient with breast cancer with a left infrahilar lung mass was treated with tamoxifen. She became asymptomatic, but after having stable disease for eight months, she developed progressive increase in the size of the mass necessitating tamoxifen withdrawal. Complete resolution of the mass occurred following withdrawal of tamoxifen. Withdrawal responses, though known to occur with additive hormonal treatment, especially complete regression of metastatic disease as seen in our patient, is not widely recognized. Thus, when clinically possible, patients should be observed off treatment for up to six weeks, before initiating a new therapeutic modality.

Breast Neoplasms↗
PubMed1989

Cisplatin for small-cell lung cancer.

Small-cell lung cancer (SCLC) is a tumor highly sensitive to chemotherapy for which combination chemotherapy is the cornerstone of treatment. Antineoplastic activity has been shown for several agents, usually in the setting of minimal prior therapy. Active agents have minimal activity when used after previous chemotherapies. Cisplatin, which has only modest activity for SCLC, has not been adequately tested in the setting of minimal prior therapy, but is probably very active. Furthermore, response to cisplatin is probably dose-dependent. Synergy between agents is very important in treatment strategies, and cisplatin is synergistic with multiple agents. The EP combination (cisplatin, etoposide) is particularly synergistic for SCLC. Unlike most other combinations, EP produces consistent responses as a salvage regimen. When used as an initial treatment regimen or to alternate with other combinations, EP approximately produces the "state-of-the-art" anticipated results. When EP is administered with concurrent chest irradiation in limited disease, it produces response and survival results similar to more aggressive regimens. Thus, EP plus chest irradiation is a reasonable combination for patients not entering investigational studies, and EP may be the foundation for more aggressive combinations. CEP (high-dose EP, cyclophosphamide) caused an increase in response frequency in extensive disease. We added cisplatin to the combination of cyclophosphamide, doxorubicin, and etoposide (PACE). This four-drug combination pilot study was stopped early because of toxicities, and follow-up now suggests that survival may be prolonged. Further study of this and similar aggressive combinations appears warranted, and the use of colony-stimulating factors may allow for acceptable toxicity and further dose escalation.

Antineoplastic Combined Chemotherapy Protocols↗