Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Nov 2008
Multicenter StudyUse of the folinic acid/5-fluorouracil/irinotecan (FOLFIRI 1) regimen in elderly patients as a first-line treatment for metastatic colorectal cancer: a Phase II study.
The aim of this study was to evaluate the effects of a combination of folinic acid, 5-fluorouracil (5FU) and irinotecan (FOLFIRI 1) administered every 2 weeks in a population of elderly subjects with advanced colorectal cancer. ⋯ The FOLFIRI 1 regimen is a valid therapeutic option for elderly patients in good clinical condition.
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Cancer Chemother. Pharmacol. · Aug 2008
Multicenter StudyTopotecan and carboplatin in patients with platinum-sensitive recurrent ovarian cancer. Results of a multicenter NOGGO: phase I/II study.
Second-line treatment with paclitaxel and carboplatin enhances survival of women with platinum-sensitive recurrent ovarian cancer (ROC). However, because of its cumulative neurotoxicity, there is a strong demand for platinum-combinations with better therapeutic index. Because of its pharmacological properties, topotecan is a good adjunct to carboplatin in this setting, but its safety and efficacy remains to be defined. ⋯ Topotecan and carboplatin is a well tolerated novel doublet option for women with platinum sensitive ROC. We encourage further studies on this approach, but to limit the doses of topotecan to 0.75 mg/m(2)/d1-3 and carboplatin AUC 5/d3.
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Cancer Chemother. Pharmacol. · Jun 2008
Multicenter StudyPharmacokinetics of a HER2 tyrosine kinase inhibitor CP-724,714 in patients with advanced malignant HER2 positive solid tumors: correlations with clinical characteristics and safety.
CP-724,714 is an orally available, small molecule, potent HER-2 tyrosine kinase inhibitor under development for the treatment of advanced HER2-overexpressing cancers. In this study, the influence of baseline clinical characteristics and pathophysiological variables on the pharmacokinetics (PK) of CP-724,714, and the correlation between PK exposure and safety were examined in patients treated in the First-in-Human trial. PK and safety were also simulated for a Phase 2 trial at the recommended Phase 2 dose (RP2D) to assess if the simulated PK exposures of CP-724,714 covered the preclinically predicted efficacious concentrations, and if the predicted incidence of hepatic toxicities (>or=CTC grade 3) was acceptable. ⋯ CP-724,714 demonstrates linear single-dose and multiple-dose PK. Both CL/F and V (dss)/F correlate with body size. Elevations of ALT, AST, and total bilirubin positively correlate with the steady-state AUC0-24 h. The Phase 2 trial simulation suggests that CP-724,714 will be well tolerated and that PK exposures will exceed the preclinically predicted efficacious level at the recommended Phase 2 dose (250 mg BID), supporting further evaluation of CP-724,714 in the Phase 2 trial.
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Cancer Chemother. Pharmacol. · Apr 2008
Multicenter StudyA phase-I study evaluating the combination of pegylated liposomal doxorubicin and paclitaxel as salvage chemotherapy in metastatic breast cancer previously treated with anthracycline.
The two main goals of this phase-I study were to determine the maximum-tolerated dose (MTD) and to characterize the toxicity of the combination of pegylated liposomal doxorubicin (PLD; Lipo-Dox) and paclitaxel (PTX) administered on a 3-week schedule in patients with metastatic breast cancer (MBC) who had previously been treated with anthracycline-based therapy. ⋯ The maximal tolerated doses of PLD and PTX are 35 and 160 mg/m2, respectively, administered every 3 weeks. The combination of PLD (30-35 mg/m2) and PTX (150-160 mg/m2) constitutes an active regimen with mild toxicity that merits further study.
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Cancer Chemother. Pharmacol. · Jan 2008
Multicenter Study Clinical TrialProspective validation of a novel IV busulfan fixed dosing for paediatric patients to improve therapeutic AUC targeting without drug monitoring.
Oral busulfan clearance is age-dependent and children experience a wide variability in plasma exposure. BSA- or age-based dosing is used with therapeutic drug monitoring (TDM) to reduce this variability. ⋯ No difference in AUC values was observed between weight strata (mean +/- SD 1248 +/- 205 micromol.min), whereas a significant difference in Bu clearance was demonstrated. This new dosing enabled to achieve a mean exposure comparable to that in adults. At dose 1, 91% of patients achieved the targeted AUC range (900-1500 micromol.min) while no patients were underexposed. At doses 9 and 13, over 75% of patients remained within that target whilst most of the others were slightly above. Successful engraftment was achieved in all patients. In conclusion, from infants to adults this new dosing enabled, without TDM and dose adjustment, to successfully target a therapeutic AUC window.