Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Mar 2002
Clinical TrialPhase I and pharmacokinetic study of SPI-77, a liposomal encapsulated dosage form of cisplatin.
To investigate the safety and pharmacokinetics of a new liposomal formulation of cisplatin, SPI-77, in patients with advanced malignancies. ⋯ The results of this phase I trial show that the pharmacokinetic behaviour of cisplatin is significantly altered by its encapsulation in Stealth liposomes. The pharmacokinetics of SPI-77 are mainly dominated by the liposomal properties, resulting in high cholesterol concentrations and relatively low concentrations of (free) platinum in plasma, WBC and tumour tissue, which may explain the observed differences between the toxicity profiles of SPI-77 and cisplatin.
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Cancer Chemother. Pharmacol. · Feb 2002
Entrapment by Cremophor EL decreases the absorption of paclitaxel from the gut.
Recent studies in mice and patients have shown that the low oral bioavailability of paclitaxel can be increased by coadministration of P-glycoprotein blockers. However, in patients an increase in the oral paclitaxel dose from 60 to 300 mg/m(2) does not result in proportionally higher plasma levels. We hypothesized that the surfactant Cremophor EL, present in the formulation of paclitaxel, may be responsible for this nonlinear absorption by entrapping paclitaxel within the intestinal lumen, probably by inclusion in micelles. ⋯ These results show that Cremophor EL prevents efficient uptake of paclitaxel from the gut, probably by entrapment within micelles. Other formulations should be developed for oral therapy with paclitaxel.
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Cancer Chemother. Pharmacol. · Dec 2001
The experimental neuroprotectant leukaemia inhibitory factor (LIF) does not compromise antitumour activity of paclitaxel, cisplatin and carboplatin.
Peripheral neuropathy caused by the anticancer agents cisplatin and paclitaxel is a significant dose-limiting toxicity of these drugs. The growth factor leukaemia inhibitory factor (LIF) has neuroprotectant activity in preclinical models of nerve injury and degeneration and is now in a phase II trial in chemotherapy-induced peripheral neuropathy (CIPN). It is therefore important to ensure that LIF neither inhibits the antitumour activity of these drugs, nor stimulates tumour growth. ⋯ These results suggest that LIF may be safely used in human trials as a neuroprotectant for patients receiving cisplatin, paclitaxel and carboplatin without concern for impairment of antitumour effect.
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Cancer Chemother. Pharmacol. · Nov 2001
Activity of irofulven (6-hydroxymethylacylfulvene) in the treatment of glioblastoma multiforme-derived xenografts in athymic mice.
This study was conducted to define the activity of irofulven in the treatment of a series of xenografts derived from human glioblastoma multiforme growing subcutaneously and intracranially in athymic nude mice. ⋯ Irofulven is active in a spectrum of human glioblastoma multiforme-derived xenografts and evaluation in patients with this neoplasm is warranted.
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Cancer Chemother. Pharmacol. · Oct 2001
ReviewRole of anti-aromatase agents in postmenopausal advanced breast cancer.
Endocrine therapy is a well-recognized approach to the treatment of postmenopausal patients with advanced breast cancer, particularly those with estrogen receptor-positive tumors. The availability of anti-aromatase agents, both reversible (nonsteroidal) and irreversible (steroidal), provides clinicians with additional hormonal treatment options. ⋯ The enhanced tolerability and superior efficacy of anti-aromatase inhibitors compared with megestrol acetate has resulted in these agents becoming the endocrine treatment of choice for women with advanced breast cancer who have progressed after tamoxifen treatment. The increased use of tamoxifen in the adjuvant setting and the demonstrated activity of aromatase inhibitors in first-line therapy will further increase the role of these agents.