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 · min) were lower than those of the control patients (88.3 mg/ml · 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. Received: 28 October 1997 / Accepted: 9 March 1998     

Conceptualizing youth empowerment within tobacco control.

This article presents a conceptual framework that was developed to guide a national evaluation of the American Legacy Foundation's (Legacy) Statewide Youth Movement Against Tobacco Use (SYMATU) program. This program was designed to develop youth-led, youth-directed initiatives within local communities. Two evaluation studies were designed and implemented from 2000 through 2003: a cross-site study that collected standard data elements across all 17 programs and a case study of five programs that collected formative data on variables thought to affect program implementation. In developing the youth empowerment (YE) conceptual framework, the authors started by reviewing literature to identify the concepts necessary for these types of initiatives and present a summary of their findings here. This article focuses on the development of the authors'overarching conceptual framework used to guide their evaluation studies. Other articles contained within this special issue present results from each of the SYMATU evaluation studies.     

A scoring system for detection of macrosomia and prediction of shoulder dystocia: a disappointment.

OBJECTIVE: To develop a scoring system for the detection of a macrosomic fetus (birth weight (BW) >or= 4000 g) and predict shoulder dystocia among large for gestational age fetuses. STUDY DESIGN: We retrospectively identified all singletons with accurate gestational age (GA) that were large for GA (abdominal circumference (AC) or estimated fetal weight (EFW) >or= 90% for GA) at >or=37 weeks with delivery within three weeks. The scoring system was: 2 points for biparietal diameter, head circumference, AC, or femur length >or=90% for GA, or if the amniotic fluid index (AFI) was >or=24 cm; for biometric parameters <90% or with AFI <24 cm, 0 points. The predictive values for detection of shoulder dystocia were calculated. RESULTS: Of the 225 cohorts that met the inclusion criteria the rate of macrosomia was 39% and among vaginal deliveries (n = 120) shoulder dystocia occurred in 12% (15/120; 95% confidence interval (CI) 7-20%). The sensitivity of EFW >or=4500 g to identify a newborn with shoulder dystocia was 0% (95% CI 0-21%), positive predictive values 0% (95% CI 0-46%), and likelihood ratio of 0. For a macrosomia score >6, the corresponding values were 20% (4-48%), 25% (5-57%) and 2.3. CONCLUSION: Though the scoring system can identify macrosomia, it offers no advantage over EFW. The scoring system and EFW are poor predictors of shoulder dystocia.     

Incidence and prognostic impact of amenorrhea during adjuvant therapy in high-risk premenopausal breast cancer: analysis of a National Cancer Institute of Canada Clinical Trials Group Study--NCIC CTG MA.5.

PURPOSE: To investigate the therapeutic impact of chemotherapy-induced amenorrhea in premenopausal patients with breast cancer. PATIENTS AND METHODS: We conducted a retrospective cohort study of a National Cancer Institute of Canada Clinical Trials Group phase III trial involving premenopausal patients randomized to receive cyclophosphamide, methotrexate, and fluorouracil (CMF), versus intensive cyclophosphamide, epirubicin, and fluorouracil (CEF). The objectives of our study were to describe the incidence of amenorrhea at 6 and 12 months post-random assignment and to determine the association of amenorrhea with relapse-free and overall survival. RESULTS: Data on 442 patients were used in our analyses. Despite the higher cumulative dose of cyclophosphamide in the CMF treatment arm, at 6 months post-random assignment, the rate of amenorrhea was higher in the CEF group (relative risk, 1.2; 95% CI, 1.0 to 1.3), with no difference at 12 months. In the receptor-positive subgroup, 6-month amenorrhea rates were not associated with prognosis. In contrast, amenorrhea at 12 months was significantly associated with relapse-free survival (hazard ratio, 0.51; 95% CI, 0.32 to 0.82; P = .005) and overall survival (hazard ratio, 0.40; 95% CI, 0.22 to 0.72; P = .002). CONCLUSION: Late chemotherapy-induced amenorrhea seems to be associated with improved outcome in patients with premenopausal, receptor-positive breast cancer.     

Summer Research Training for Medical Students: Impact on Research Self‐Efficacy

There is a well‐documented shortage of physician researchers, and numerous training programs have been launched to facilitate development of new physician scientists. Short‐term research training programs are the most practical form of research exposure for most medical students, and the summer between their first and second years of medical school is generally the longest period they can devote solely to research. The goal of short‐term training programs is to whet the students’ appetite for research and spark their interest in the field. Relatively little research has been done to test the effectiveness of short‐term research training programs. In an effort to examine short‐term effects of three different NIH‐funded summer research training programs for medical students, we assessed the trainees’ (N = 75) research self‐efficacy prior to and after the programs using an 11‐item scale. These hands‐on training programs combined experiential, didactic, and mentoring elements. The students demonstrated a significant increase in their self‐efficacy for research. Trainees’ gender, ranking of their school, type of research, and specific content of research project did not predict improvement. Effect sizes for different types of items on the scale varied, with the largest gain seen in research methodology and communication of study findings.     

Health Care Utilization by Patients with Temporomandibular Joint Disorders

The claims data base of a large New England managed care organization was used to compare the health care utilization patterns of patients with TMJ disorders to non-TMJ subjects. Inpatient, outpatient and psychiatric claims data were examined over a wide range of diagnostic categories. Age and sex adjusted results showed that, overall, patients with TMJ disorders were greater utilizers of health care services and had higher associated costs than non-TMJ subjects. For some of the major diagnostic categories, such as nervous, respiratory, circulatory, and digestive, the inpatient and outpatient claims differences in utilization and costs were as large as 3 to 1. For only one diagnostic category, pregnancy and childbirth, were utilization and costs greater for non-TMJ subjects than TMJ patients. The psychiatric claims for TMJ patients exhibited differences that were at least twice as large as those for the non-TMJ subjects.