Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Dec 2009
Phase II and pharmacokinetic trial of rebeccamycin analog in advanced biliary cancers.
Advanced cancers of the bile duct and gallbladder carry an ominous prognosis. Rebeccamycin analogue (RA) is a novel antitumor antibiotic where phase I trials suggested clinical efficacy in patients with biliary cancers. ⋯ Although RA has a response rate of 5% in advanced biliary cancers, it is associated with significant numbers of patients experiencing prolonged stable disease. Biliary concentrations of RA are significantly greater than plasma concentrations.
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Cancer Chemother. Pharmacol. · Dec 2009
Phase I and pharmacokinetic study of cisplatin and troxacitabine administered intravenously every 28 days in patients with advanced solid malignancies.
To assess the feasibility of administering troxacitabine, an L-nucleoside analog that is not a substrate for deoxycytidine deaminase, in combination with cisplatin, to identify pharmacokinetic interactions, and to seek preliminary evidence of antitumor activity. ⋯ The combination of cisplatin and troxacitabine produces dose-limiting myelosuppression at lower doses of troxacitabine than single agent doses. The recommended phase II doses of cisplatin/troxacitabine are 75/6.4 and 50/4.8 mg/m(2), every 4 weeks, for MP and HP patients, respectively. The addition of cisplatin did not substantially alter the pharmacokinetic behavior of troxacitabine.
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Cancer Chemother. Pharmacol. · Nov 2009
Enhancement of cisplatin cytotoxicity by SAHA involves endoplasmic reticulum stress-mediated apoptosis in oral squamous cell carcinoma cells.
The histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), enhances cisplatin [cis-diammine dichloroplatinum (II)] (CDDP)-induced apoptosis in the oral squamous cell carcinoma (OSCC) cell line by complex, multifunctional mechanisms. We investigated the role of endoplasmic reticulum (ER) stress in the enhancing effect of SAHA on CDDP, compared with the ER stressor thapsigargin. ⋯ These data indicate that up-regulation of specific-ER stress-associated events is an integral part of the mechanism by which SAHA enhances CDDP-induced apoptosis, and PP1 up-regulation followed by Akt dephosphorylation plays an important role in SAHA-enhanced CDDP apoptosis.
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Cancer Chemother. Pharmacol. · Sep 2009
ReviewTemozolomide in malignant gliomas: current use and future targets.
Temozolomide (TMZ) is an oral alkylating agent that is regarded as a tolerable and effective drug. When combined with radiotherapy in patients with newly diagnosed glioblastoma, survival is significantly prolonged. This finding has led to widespread use of TMZ for patients with this disease. We summarize developing concerns regarding the use of TMZ, imaging of malignant gliomas, and the pharmacology of TMZ-mechanism of action, scheduling and strategies for overcoming resistance.
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Cancer Chemother. Pharmacol. · Aug 2009
Multicenter StudyPegylated liposomal doxorubicin (CAELYX) in patients with advanced ovarian cancer: results of a German multicenter observational study.
Pegylated liposomal doxorubicin (PLD, CAELYX) has demonstrated activity in several phase-III trials and has been approved for the therapy of relapsed ovarian cancer after platinum treatment. Aim of this observational study was to analyze the efficacy and toxicity profile of PLD under routine clinical conditions and without the general restrictions of defined inclusion and exclusion criteria of clinical trials. ⋯ PLD is safe and effective in patients with relapsed ovarian cancer, even after numerous previous treatment regimens. A dose of 40 mg/m(2) every 28 days seems to be an effective and well-tolerated therapeutic option in advanced ovarian cancer with a low incidence of hematological toxicities and acceptable non-hematological toxicities.