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James F Cleary

Publications and source records attributed to James F Cleary.

6 recordsLinked to original sources
PubMed2005

Effect of exemestane on tamoxifen pharmacokinetics in postmenopausal women treated for breast cancer.

PURPOSE: Rodent models of human breast cancer suggest that the combination of the steroidal aromatase inhibitor exemestane with tamoxifen may have additive activity. Clinical trials combining tamoxifen with letrozole or anastrazole have shown minor pharmacokinetic drug interactions. We did an open-label crossover clinical trial of the effect of exemestane on tamoxifen pharmacokinetics. DESIGN: Thirty-two postmenopausal women who were clinically disease-free following primary treatments for breast cancer receiving tamoxifen for at least 3 months were studied. Blood was collected for pharmacokinetic analysis after at least 4 months of receiving 20 mg tamoxifen daily. Subjects then began 8 weeks of oral exemestane (25 mg daily), followed by another set of blood samples. RESULTS: There were no serious toxicities noted when the two drugs were combined. There was no significant effect of exemestane on the area under the plasma concentration versus time curve (AUC) of tamoxifen at steady state before [3.04 mg h/L; 90% confidence interval (90% CI), 2.71-3.44] and during exemestane treatment (3.05 mg h/L; 90% CI, 2.72-3.41). There were no significant changes in the formation of primary tamoxifen metabolites. Oral clearance of exemestane averaged 602 L/h based on an average plasma exemestane AUC of 41.5 microg h/L (90% CI, 36.7-62.6). Plasma concentrations of estradiol, estrone, and estrone sulfate decreased when exemestane was begun; estradiol concentrations consistently decreased below the limit of quantitation. CONCLUSIONS: There is no pharmacokinetic interaction between tamoxifen and exemestane. No modification in the standard regimen of either drug seems to be indicated if they are used in combination. The combination of the two drugs was well tolerated during the 8-week evaluation period.

Adult↗
PubMed2005

Endocrine effects of tamoxifen plus exemestane in postmenopausal women with breast cancer.

PURPOSE: In some specific circumstances, combined hormonal therapies for breast cancer seem to be more effective than single maneuvers. In two laboratory mammary cancer models, the combination of the aromatase inactivator exemestane plus tamoxifen gives a higher response rate than is found with either agent alone. To evaluate the endocrine effects of the combination of exemestane and tamoxifen, we studied 33 postmenopausal women disease-free following primary treatments for breast cancer who were taking tamoxifen for at least 3 months. DESIGN: After observation for symptoms on tamoxifen for 4 weeks, blood samples were taken and patients were begun additionally on exemestane 25 mg p.o. qd. Eight weeks later, blood samples were again taken, and exemestane was discontinued. RESULTS: A decrease in alkaline phosphatase was found with exemestane treatment (P = 0.06), whereas no change in osteocalcin level was observed. A decrease in high-density lipoprotein cholesterol level was found (P = 0.0025), whereas total cholesterol, low-density lipoprotein cholesterol and triglyceride levels showed no changes with exemestane treatment. Estradiol, estrone, and estrone sulfate levels decreased to immeasurable or very low levels with exemestane treatment (all P < 0.001). No significant changes in frequencies of common drug-associated side effects, such as vasomotor symptoms or weight change, were found. CONCLUSIONS: Based on the absence of adverse endocrine effects with the addition of exemestane to tamoxifen therapy observed in this study, further clinical evaluation of the efficacy of this combination is warranted.

Adult↗
PubMed2005

Incident pain.

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Activities of Daily Living↗
PubMed2004

Consensus statement: Palliative and supportive care in advanced heart failure.

BACKGROUND: A consensus conference was convened to define the current state and important gaps in knowledge and needed research on "Palliative and Supportive Care in Advanced Heart Failure." EVIDENCE: Evidence was drawn from expert opinion and from extensive review of the medical literature, evidence-based guidelines, and reviews. CONCLUSIONS: The conference identified gaps in current knowledge, practice, and research relating to prognostication, symptom management, and supportive care for advanced heart failure (HF). Specific conclusions include: (1) although supportive care should be integrated throughout treatment of patients with advanced HF, data are needed to understand how to best decrease physical and psychosocial burdens of advanced HF and to meet patient and family needs; (2) prognostication in advanced HF is difficult and data are needed to understand which patients will benefit from which interventions and how best to counsel patients with advanced HF; (3) research is needed to identify which interventions improve quality of life and best achieve the outcomes desired by patients and family members; (4) care should be coordinated between sites of care, and barriers to evidence-based practice must be addressed programmatically; and (5) more research is needed to identify the content and technique of communicating prognosis and treatment options with patients with advanced HF; physicians caring for patients with advanced HF must develop skills to better integrate the patient's preferences into the goals of care.

Counseling↗
PubMed2002

Phase I clinical and pharmacokinetic trial of the cyclin-dependent kinase inhibitor flavopiridol.

PURPOSE: Flavopiridol (NSC 649890) is a synthetic flavone possessing significant antitumor activity in preclinical models. Flavopiridol is capable of inducing cell cycle arrest and apoptosis, presumably through its potent, specific inhibition of cyclin-dependent kinases. We conducted a phase I trial and pharmacokinetic study of flavopiridol given as a 72-h continuous intravenous infusion repeated every 2 weeks. METHODS: A total of 38 patients were treated at dose levels of 8, 16, 26.6, 40, 50 and 56 mg/m(2)/24 h. During the first infusion, plasma was sampled at 24, 48 and 72 h to determine steady-state concentrations, and peripheral blood lymphocytes were assessed by flow cytometry for evidence of apoptosis. Additional postinfusion pharmacokinetic sampling was done at the 40 and 50 mg/m(2)/24 h dose levels. RESULTS: Gastrointestinal toxicity was dose limiting, with diarrhea being the predominant symptom. Symptomatic orthostatic hypotension was also frequently noted. Several patients experienced tumor-specific pain during their infusions. The maximum tolerated dose (MTD) was determined to be 40 mg/m(2)/24 h. A patient with metastatic gastric cancer at this dose level had a complete response and remained disease-free for more than 48 months after completing therapy. Plasma concentrations at 24 h into the infusion were 94% of those achieved at steady state. Steady-state plasma flavopiridol concentrations at the MTD were 416.6+/-98.9 micro M. These concentrations are at or above those needed to see cell cycle arrest and apoptosis in vitro. The mean clearance of flavopiridol over the dose range was 11.3+/-3.9 l/h per m(2), similar to values obtained preclinically. Elimination was biphasic. The terminal half-life at the MTD was 26.0 h. No significant differences in pharmacokinetic parameters were noted between males and females. Patients taking cholestyramine to ameliorate flavopiridol-induced diarrhea had lower steady-state plasma concentrations. There was no significant change in the cell cycle parameters of peripheral blood lymphocytes analyzed by flow cytometry. CONCLUSIONS: The MTD and recommended phase II dose of flavopiridol given by this schedule is 40 mg/m(2)/24 h. The manageable gastrointestinal toxicity, early signs of clinical activity and lack of hematologic toxicity make further exploration in combination trials warranted.

Adult↗