Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Apr 2008
Pharmacokinetics of decitabine administered as a 3-h infusion to patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).
In this study, pharmacokinetics (PK) of decitabine administered as a 3-h intravenous infusion of 15 mg/m2 every 8 h for 3 days (cycles repeated every 6 weeks) was evaluated in patients with MDS or AML. ⋯ Decitabine dosed at 15 mg/m2 iv every 8 h for 3 days resulted in a predictable and manageable toxicity profile in patients with MDS/AML. The repeated dosing did not result in systemic accumulation of the drug, and decitabine PK remained unchanged from cycle to cycle.
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Cancer Chemother. Pharmacol. · Mar 2008
Improvement in intraperitoneal intraoperative cisplatin exposure based on pharmacokinetic analysis in patients with ovarian cancer.
Ovarian cancer is the leading cause of gynecological cancer-related death in Western countries. The present treatment standards for ovarian cancer are based on the association of debulking surgery with platinum-based chemotherapy. Another strategy that could be further investigated is intraperitoneal chemotherapy (IP). ⋯ However, this improvement is associated with an increase in serum Pt levels and resulting renal toxicities. An attractive solution would be to decrease Pt transfer from peritoneum to bloodstream. A phase 1 study using intraoperative IP epinephrine in order to decrease this transfer is presently being carried out.
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Cancer Chemother. Pharmacol. · Mar 2008
A phase II study of trastuzumab and capecitabine for patients with HER2-overexpressing metastatic breast cancer: Japan Breast Cancer Research Network (JBCRN) 00 Trial.
To determine the response rate and toxicity profile of trastuzumab and capecitabine in women with HER2-overexpressing advanced breast cancer. ⋯ Trastuzumab in combination with capecitabine is highly active in women with HER2-overexpressing metastatic breast cancer and is well tolerated.
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Cancer Chemother. Pharmacol. · Feb 2008
Pharmacokinetics of gemcitabine in tumor and non-tumor extracellular fluid of brain: an in vivo assessment in rats employing intracerebral microdialysis.
Gemcitabine is a pyrimidine nucleoside analogue anticancer agent that has shown promising anti-tumor activity in several experimental models of brain tumor. However, the pharmacokinetic behavior of gemcitabine in the central nervous system, especially in brain tumors is currently not well understood. In this study we evaluated the gemcitabine brain extracellular fluid (ECF) in normal rats and in ECF obtained from tumor- and tumor-free regions of glioma-bearing rats, to better understand the availability of the drug to brain and brain tumors. ⋯ Our findings suggest that the overall brain exposure to gemcitabine is likely to be low as evident from the relative brain distribution coefficient of <0.1. However, the exposure is likely to be considerably higher in the brain tumor relative to tumor-free regions of the brain. The higher drug levels in brain tumor compared to the non-tumor region may facilitate selectively higher cytotoxicity against brain tumor cells.
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Cancer Chemother. Pharmacol. · Jan 2008
A phase II trial of modified weekly irinotecan and cisplatin for chemotherapy-naïve patients with metastatic or recurrent squamous cell carcinoma of the esophagus.
This phase II study assessed the efficacy and toxicity profile of a modified weekly irinotecan and cisplatin for chemotherapy-naïve patients with metastatic/recurrent esophageal squamous cell carcinoma (SQCC). ⋯ This modified weekly irinotecan and cisplatin failed to ameliorate hematologic toxicity and to improve efficacy. However, easy administration and favorable non-hematologic toxicity as well as modest anti-tumor activity against metastatic or recurrent esophageal SQCC can make this regimen a potential treatment option, given the complexity of administration and toxicity of conventional infusional 5-FU and cisplatin.