Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · May 2005
Clinical TrialA phase I, dose-finding study of irinotecan (CPT-11) short i.v. infusion combined with fixed dose of 5-fluorouracil (5-FU) protracted i.v. infusion in adult patients with advanced solid tumours.
Irinotecan (CPT-11) and 5-fluorouracil (5-FU) are effective cytotoxic agents in the treatment of solid tumours. Continuous i.v. infusion (CI) of 5-FU is significantly more active and better tolerated than bolus i.v. 5-FU. This phase I pharmacokinetic and clinical study evaluated escalating CPT-11 doses administered every 3 weeks combined with a fixed dose of 5-FU CI over 14 days to find the maximum tolerated dose (MTD) of this combined chemotherapy. ⋯ CPT-11 300 mg/m(2) + 5-FU 250 mg/m(2) protracted infusion is the recommended dose for phase II trials, neutropenia and diarrhoea being the dose-limiting toxicities.
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Cancer Chemother. Pharmacol. · Jan 2005
Pharmacokinetics and neutrophil toxicity of paclitaxel orally administered in mice with recombinant interleukin-2.
Intrinsic P-glycoprotein (P-gp) expression in the gut limits paclitaxel uptake and, thus, its bioavailability when administered orally. Interleukin-2 has been reported to be a P-gp modulator in vitro and in vivo in mice. In the work described here, the effects of interleukin-2 pretreatment on pharmacokinetics and toxicity of paclitaxel orally administered were investigated. ⋯ We found that a 3-day pretreatment with rIL2 had some in vivo inhibitory effects on P-gp activity for a short period after oral dosing of paclitaxel. Those results encourage further investigation of the effect of rIL2 on the overall exposure of paclitaxel. On the other hand, it seems that the joint administration of the two drugs did not increase the risk of myelosuppression, which might be worth knowing to treat advanced cancers.
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Cancer Chemother. Pharmacol. · Nov 2004
Randomized Controlled Trial Multicenter Study Comparative Study Clinical TrialA randomized cross-over trial to determine the effect of Cremophor EL on the pharmacodynamics and pharmacokinetics of carboplatin chemotherapy.
Paclitaxel, when combined with carboplatin, exhibits a platelet-sparing effect. Paclitaxel is formulated in Cremophor EL (CrEL), which has been shown in preclinical models to reduce haematological toxicity from radiotherapy and chemotherapy. We sought to determine the effect of a 3-h infusion of 20 ml/m2 (equivalent to 175 mg/m2 paclitaxel) CrEL on myelosuppression following carboplatin chemotherapy, and the effect of CrEL on carboplatin pharmacokinetics. ⋯ CrEL at this dose and schedule does not appear to be a major contributory factor to the platelet-sparing effect of paclitaxel when combined with carboplatin, nor does it alter the pharmacokinetics of carboplatin.
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Cancer Chemother. Pharmacol. · Nov 2004
Clinical TrialPhase II study of doxorubicin and cisplatin in patients with metastatic hepatocellular carcinoma.
The outcome of systemic chemotherapy in metastatic hepatocellular carcinoma (HCC) patients had been disappointing. Based on the demonstrated antitumor activities and different mechanisms of action and toxicity profiles, we designed a phase II trial of combination therapy with doxorubicin and cisplatin in metastatic HCC patients anticipating a synergistic interaction of the combination. ⋯ Combination chemotherapy with doxorubicin and cisplatin in metastatic HCC patients showed modest antitumor activity with relatively tolerable adverse effects. The objective response rate of the regimen was comparable to those found in other phase II trials, but the search for the optimal chemotherapy should be continued.
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Cancer Chemother. Pharmacol. · Nov 2004
Cyclooxygenase inhibitors and thalidomide ameliorate vincristine-induced hyperalgesia in rats.
In this study ibuprofen (50.0 mg/kg, i.p.), rofecoxib (10.0 mg/kg, i.p.) and thalidomide (50.0 mg/kg, oral) were shown to prevent vincristine-induced mechanical hyperalgesia. Sprague-Dawley rats were injected every other day with vincristine (0.1 mg/kg) over 13 days. The animals were cotreated daily with vehicle (saline), ibuprofen, rofecoxib or thalidomide throughout the period of vincristine treatment. ⋯ All three active drugs showed an antihyperalgesic effect on the responses to mechanical stimulation of the hind paw that was significant from day 5 for ibuprofen and thalidomide and from day 7 for rofecoxib. Thermal thresholds increased after the administration of both the NSAIDs and thalidomide. Rofecoxib was the only drug to show any beneficial effect in protecting the animals from failure to gain body weight.