Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Sep 2010
Randomized Controlled TrialRandomized controlled phase II comparison study of concurrent chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil versus CCRT with cisplatin, 5-fluorouracil, methotrexate and leucovorin in patients with locally advanced squamous cell carcinoma of the head and neck.
We compared concurrent chemoradiotherapy (CCRT) with docetaxel, cisplatin (CDDP), and 5-fluorouracil (5-FU) (TPF) with CCRT with CDDP, 5-FU, methotrexate and leucovorin (PFML) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) in terms of safety and efficacy on survival. A total of 100 patients were enrolled. The TPF group received CCRT with the TPF regimen [docetaxel (50 mg/m(2): day 1), CDDP (60 mg/m(2): day 4), and continuous 5-FU infusion (600 mg/m(2)/day: days 1-5)]. ⋯ The overall response rates after CCRT were 98 with 90% of a pathologically complete response (pCR) in the TPF group and 94 with 77% in the PFML group. For grade 3/4 adverse events, mucositis was more frequent in the PMFL group, and the TPF group showed a higher incidence of hematological toxicity. CCRT with TPF or PMFL for advanced SCCHN was tolerable and produced excellent survival rates.
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Cancer Chemother. Pharmacol. · May 2009
Randomized Controlled Trial Multicenter StudyMechanistic population pharmacokinetics of total and unbound paclitaxel for a new nanodroplet formulation versus Taxol in cancer patients.
Our objectives were (1) to compare the disposition and in vivo release of paclitaxel between a tocopherol-based Cremophor-free formulation (Tocosol Paclitaxel) and Cremophor EL-formulated paclitaxel (Taxol) in human subjects, and (2) to develop a mechanistic model for unbound and total paclitaxel pharmacokinetics. ⋯ Population pharmacokinetic analysis indicated linear disposition and a potentially higher bioavailability of unbound paclitaxel following Tocosol Paclitaxel administration due to direct release at the target site. The prolonged release of Tocosol Paclitaxel supports 15 min paclitaxel infusions. This mechanistic model may be important for development of prolonged release formulations that distribute in and from the systemic circulation.
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Cancer Chemother. Pharmacol. · Jul 2008
Randomized Controlled TrialTritherapy with fluorouracil/leucovorin, irinotecan and oxaliplatin (FOLFIRINOX): a phase II study in colorectal cancer patients with non-resectable liver metastases.
To assess the rate of R(0) resection of liver metastases achieved after chemotherapy with FOLFIRINOX. ⋯ FOLFIRINOX, with an acceptable toxicity profile, shows a high response rate in liver metastases from colorectal cancer. The rate of hepatic resection in patients initially not resectable, is attractive and warrants further assessment of this regimen in randomized studies compared to standard regimens.
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Cancer Chemother. Pharmacol. · Apr 2008
Randomized Controlled TrialAn open-label study to evaluate dose and cycle dependence of the pharmacokinetics of pegylated liposomal doxorubicin.
There are no definitive data in humans on the dose dependence and/or cycle dependence of the pharmacokinetics (PK) of pegylated liposomal doxorubicin (PLD). This study examined the PK of PLD across a twofold dose variation and along 3 cycles. ⋯ While the PK of PLD is not dose-dependent within the dose range of 30-60 mg/m(2), there is evidence of a cycle-dependent effect that results in inhibition of clearance when patients receive successive cycles of PLD. These results suggest the need for dose adjustments of PLD upon retreatment to minimize the risk of toxicity.
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Cancer Chemother. Pharmacol. · May 2006
Randomized Controlled TrialClinical and pharmacokinetic study evaluating the effect of food on the disposition of 9-nitrocamptothecin and its 9-aminocamptothecin metabolite in patients with solid tumors.
9-Nitrocamptothecin (9NC) is an orally administered camptothecin analogue that has completed phase III trials for pancreatic cancer. In biological matrices, camptothecin analogues exist in equilibrium between the active-lactone (LAC) and inactive-hydroxy acid (HA) forms. 9NC has been administered on an empty stomach; however, it is unclear if food alters the absorption and disposition of 9NC and its 9-aminocamptothecin (9AC) active-metabolite. Thus, we evaluated the disposition of 9NC and 9AC after administration of 9NC under fasting conditions and after a standard meal. ⋯ Co-administration of 9NC with food reduces the oral absorption of 9NC; however, there was no difference in the exposure of 9AC. The is high interpatient variability in the effect of food on the absorption of 9NC and the interpatient variability in the effect of food on the disposition of 9AC is even greater when compared to 9NC.