Showing papers by "Thomas W. Flaig published in 2006"

A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients.

Abstract: Silibinin is a polyphenolic flavonoid isolated from milk thistle with anti-neoplastic activity in several in vitro and in vivo models of cancer, including prostate cancer Silybin-phytosome is a commercially available formulation containing silibinin This trial was designed to assess the toxicity of high-dose silybin-phytosome and recommend a phase II dose Silybin-phytosome was administered orally to prostate cancer patients, giving 25-20 g daily, in three divided doses Each course was 4 weeks in duration Thirteen patients received a total of 91 courses of silybin-phytosome Baseline patient characteristics included: median age of 70 years, median baseline prostate specific antigen (PSA) of 43 ng/ml, and a median ECOG performance status of 0 The most prominent adverse event was hyperbilirubinemia, with grade 1-2 bilirubin elevations in 9 of the 13 patients The only grade 3 toxicity observed was elevation of alanine aminotransferase (ALT) in one patient; no grade 4 toxicity was noted No objective PSA responses were observed We conclude that 13 g of oral silybin-phytosome daily, in 3 divided doses, appears to be well tolerated in patients with advanced prostate cancer and is the recommended phase II dose Asymptomatic liver toxicity is the most commonly seen adverse event

A phase II trial of dexamethasone, vitamin D, and carboplatin in patients with hormone-refractory prostate cancer.

Abstract: BACKGROUND. A Phase II prospective trial was performed to study the efficacy of combination therapy with dexamethasone, calcitriol (1,25-dihydroxyvitamin D3), and carboplatin in patients with hormone-refractory prostate cancer (HRPC). Preclinical data from prostate cancer cell lines suggested a synergistic effect of these therapies. METHODS. All patients had pathologically confirmed prostate cancer with at least 2 consecutive increases in prostate-specific antigen (PSA). Treatment started with 1 mg of oral dexamethasone given daily with 0.5 mcg of daily calcitriol added at the start of Week 5. Carboplatin (area under the concentration time curve = 2) was started at the beginning of Week 7. Initially, carboplatin was given weekly; however, the protocol was changed later to give carboplatin for the first 4 weeks of a 6-week cycle. Of 40 patients who consented to participate, 6 patients were ineligible or declined to start therapy, leaving 34 treated patients. The median follow-up was 80.7 weeks (range, 11.5–260 weeks). RESULTS. A formal PSA response was seen in 13 of 34 treated patients (38.2%; 95% confidence interval [95% CI], 22.2–56.4%). The median overall survival was 97.7 weeks (95% CI, 61–114 weeks). Significant adverse events that were observed during the trial period included 2 deaths (myocardial infarction and cardiogenic shock), 4 patients with Grade 3 neutropenia (according to the National Cancer Institute Common Toxicity Criteria, version 2.0), 2 patients with thrombosis, 2 patients with inflammatory bowel symptoms, and 2 patients with new-onset diabetes mellitus. CONCLUSIONS. The novel combination of dexamethasone, calcitriol, and carboplatin for patients with HRPC produced a PSA response in 13 of 34 patients and had an acceptable side-effect profile. Cancer 2006. © 2006 American Cancer Society.

Mitoxantrone-Associated Acute Myelogenous Leukemia in a Patient with High-Risk Adenocarcinoma of the Prostate: A Case Report and Brief Review

Abstract: Background: Mitoxantrone, a topoisomerase II-targeted drug, is used to treat several conditions and is a Food and Drug Administration approved chemotherapeutic agent for the treatment of advanced carcinoma of the prostate. Case Report: A 64-year-old male with high-risk prostate cancer was treated with adjuvant mitoxantrone (12 mg/meter2) every 3 weeks for 6 cycles. Approximately 10 months after finishing therapy, he was diagnosed with an inv [] Acute Myelogenous Leukemia (AML). Despite aggressive treatment and support, the patient had a rapidly fatal clinical course. Conclusion: Despite its regular use in this setting, this is the first reported case of treatment-associated AML after mitoxantrone in prostate cancer.