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Biomedical subjects

C Cavanaugh

Publications and source records attributed to C Cavanaugh.

7 recordsLinked to original sources
PubMed1998

Pharmacokinetic interaction between ondansetron and cyclophosphamide during high-dose chemotherapy for breast cancer.

PURPOSE: Both ondansetron and cyclophosphamide are thought to be metabolized by hepatic microsomal processes. The purpose of this study was to evaluate the potential pharmacokinetic interactions between ondansetron and high-dose alkylating agent chemotherapy. METHODS: A total of 54 breast cancer patients receiving high-dose cyclophosphamide, cisplatin and carmustine were treated prospectively in four sequential cohorts. Cohorts I and II received continuous infusions of both ondansetron and prochlorperazine, and cohorts III and IV received a continuous infusion of ondansetron alone at the same doses. All patients received lorazepam every 4 h. A group of 75 matched historical controls had received a continuous infusion of prochlorperazine with lorazepam. Pharmacokinetic monitoring of each drug used in the high-dose chemotherapy regimen was conducted. RESULTS: Median AUCs of cyclophosphamide in patients receiving ondansetron (73.6 mg/ml x min) were lower than those of the control patients (88.3 mg/ml x min, n = 75, P = 0.0004), but the median cisplatin AUC was approximately 10% higher and no difference in the disposition of carmustine was demonstrated. Patients treated with ondansetron displayed a higher frequency of headaches than the controls. The frequency of achieving complete emetic control was greater in the ondansetron + prochlorperazine groups compared to the ondansetron alone groups and was greater in both these groups than in the prochlorperazine alone group on the first day of therapy only. CONCLUSION: Ondansetron altered the systemic exposure to cyclophosphamide when these agents were administered concomitantly. Ondansetron did not substantially improve overall emetic control when used alone but may improve control in combination with prochlorperazine. Future randomized studies are needed to delineate the effect of ondansetron on the disposition of the active cyclophosphamide metabolites so that clinical implications can be addressed.

Antiemetics↗
PubMed1997

Activity of paclitaxel liposome formulations against human ovarian tumor xenografts.

Although the current clinical formulation of paclitaxel (Taxol) is an important new anti-cancer agent, it has significant side effects, some of which are related to its formulation in Cremophor/ethanol. Paclitaxel is difficult to formulate for i.v. administration because of its poor aqueous solubility. Here, we report the therapeutic effects of 2 liposome formulations of paclitaxel against human ovarian A121 tumor growing as an s.c. xenograft in athymic nude mice. The liposome formulations used were ETL and TTL, which have I or 3 lipid components, respectively. TTL was used as a reconstituted lyophilate or as a stable aqueous suspension. ETL was used as a reconstituted lyophilate only. Both paclitaxel-liposome formulations were much better tolerated than Taxol after i.v. or i.p. administration. The acute reactions seen after Taxol administration did not occur when paclitaxel-liposome formulations were administered. All ETL and TTL preparations significantly delayed A121 tumor growth similarly to Taxol at equivalent doses and schedules. Based on pharmacokinetic data, it is possible that paclitaxel rapidly dissociates from ETL or TTL after i.v. administration and distributes in a manner similarly to Taxol. ETL and TTL formulations may be useful clinically not only for eliminating toxic effects of the Cremophor/ethanol vehicle but also for allowing alterations in route and schedule of drug administration.

Animals↗
PubMed1994

The use of intensive clinic support to permit outpatient autologous bone marrow transplantation for breast cancer.

Recent studies have explored feasibility and cost considerations of administering high-dose chemotherapy with hematopoietic support in the outpatient setting. Between October 1991 and April 1993, we studied 110 women with primary metastatic breast cancer undergoing high-dose chemotherapy with hematopoietic support. Ninety-two patients were managed in an outpatient clinic after high-dose chemotherapy and autologous bone marrow transplantation and peripheral blood progenitor cells. The remaining 18 patients received the same high-dose treatment and hematopoietic support in the hospital and were discharged to a nearby hotel each night; these patients were the pilot group for this effort and also served as a control group. High-dose chemotherapy consisted of cyclophosphamide/cisplatin/carmustine. Chemotherapy was well tolerated, allowing 95% of 65 eligible patients enrolled since November 1992 to be discharged soon after chemotherapy for outpatient posttransplant support. Approximately 70% of these patients required either no hospital readmission or brief readmissions of 1 to 4 days. Median days of hospitalization required for historical groups of patients receiving high-dose chemotherapy plus bone marrow support as inpatient therapy, high-dose chemotherapy with colony-stimulating factor-primed peripheral blood progenitor cells and autologous bone marrow transplantation as inpatient therapy in a traditional transplant model, and outpatient management of autologous bone marrow transplantation patients were 37, 24.5, and 7 days, respectively, despite the same high-dose chemotherapy. Charges related to the transplant procedure were reduced by 50% over the last 2 to 5 years using the outpatient management approach. This procedure may be applicable to patients with other forms of cancer receiving intensive chemotherapeutic regimens. The use of outpatient management in a transplant setting is highly cost effective.

Adult↗
PubMed1991

Mechanisms of H2O2-mediated injury to type II cell surfactant metabolism and protection with PEG-catalase.

Alterations in type II pneumocyte function, including surfactant biosynthesis, may play a significant role in the development and pathophysiology of oxidant-induced lung injury. The results of this study showed that type II cells exposed to 50-300 microM H2O2 demonstrated a dose-dependent decrease in phosphatidylcholine (PC) synthesis with only minimal changes in cell viability. The activities of the choline-phosphate cytidyltransferase and cholinephosphotransferase, specific enzymes of PC synthesis, were not significantly decreased by the exposure. However, the activity of glycerol-3-phosphate acyltransferase, a sulfhydryl-dependent enzyme involved in an early stage of phospholipid synthesis, was decreased by the exposures in a manner that was similar to that seen for PC synthesis. Further studies showed that incubation of type II cells with polyethylene glycol-conjugated catalase for 1 h resulted in an increase in the cell-associated catalase activity (53 +/- 5 vs. 6.7 +/- 1.5 units/mg protein for controls). Confocal microscopy analysis showed that a significant portion of this activity was located intracellularly. More importantly, these cells were protected from changes in PC synthesis rates when subsequently incubated with 300 microM H2O2. These results indicate that the deleterious effects of H2O2 on type II cell surfactant synthesis may be pharmacologically modified in vitro, a concept that may have utility with regard to the modulation of in vivo lung injuries.

Animals↗
PubMed1989

Dental esthetic satisfaction in adults.

This study determined the influence of teeth, mouth, and face on self-image and personal esthetic satisfaction in adults. A random sample of 125 patients completed a five-item questionnaire about personal esthetic satisfaction and oral self-image. As a group, general dental variables were stronger predictors of esthetic satisfaction than orthodontic variables (P less than .01). Discrepancies between clinical findings and patterns of self-perception and satisfaction suggest the dentist and patient should plan together for esthetic dental treatment.

Adolescent↗
PubMed1987

Microvascular function in skin windows.

The dermal microvasculature is an integral component of skin windows. However, in spite of the obvious dependence of the skin window model on vascular function, its almost exclusive application has been the study of leukocyte function and recovery of the cellular components of inflammatory exudates. In the studies reported here, skin window chambers were employed for assessment of function of the underlying microvasculature in rats given intravenous infusions of Evans blue dye or colloidal carbon. Increased vascular permeability was documented by photometric measurement of Evans blue dye, and vascular labeling of dermal vessels with colloidal carbon was assessed histologically. Zymosan-activated serum elicited accumulation of both leukocytes and Evans blue dye in chamber fluid overlying skin windows, confirming the responsiveness of the preparations. With serotonin as a model vasoactive substance, both increased vascular permeability and vascular labeling were directly related to serotonin concentration in the chamber fluid. It is estimated that plasma exudates were distributed as approximately 10% in the fluid and 90% in the dermis. Finally, serotonin-induced exudates recovered from the 0.3-ml chambers were estimated to be up to 3 microliter of plasma based on Evans blue dye measurement or up to 70 micrograms of protein based on Lowry assay. Thus, soluble components of skin window exudates were recovered for examination, and the dermal microvasculature was shown to be an important functional component of the skin window model that was directly accessible for study.

Animals↗