Lifestyle habits as a contributor to anti-cancer treatment failure

Lifestyle may have serious consequences for cancer treatment outcome, which is a fact that both physicians and patients are often not explicitly aware of, thereby unwillingly exposing the patient to possible danger. In certain cases, patient behaviour can lead to potentially life-threatening adverse events, whilst in other cases the clinical benefit of anti-cancer therapy can be diminished. In this review, we focus on the role of certain habits (like cigarette smoking, alcohol use and the use of complementary and alternative medicine) and discuss the effects they may have on anti-cancer medication. Also patient compliance to prescribed anti-cancer drugs is a factor frequently overlooked if treatment does not follow the expectations, which gains importance with the increasingly frequent prescription of oral anti-cancer agents. (c) 2007 Elsevier Ltd. All rights reserved

Flat-fixed dosing of irinotecan: influence on pharmacokinetic and pharmacodynamic variability

PURPOSE: In a previous analysis, it was shown that body-surface area (BSA) is not a predictor of irinotecan pharmacokinetic parameters. Here, we prospectively evaluated the effects of administering a flat-fixed irinotecan dose to cancer patients, regardless of BSA. EXPERIMENTAL DESIGN: Twenty-six cancer patients (12 females) received a fixed irinotecan dose of 600 mg, given as a 90-min i.v. infusion. Plasma concentrations of irinotecan and its metabolites SN-38 (7-ethyl-10-hydroxycamptothecin) and SN-38G (SN-38 glucuronide) were measured during the first cycle and analyzed using nonlinear mixed-effect modeling. Data were compared with those obtained in 47 cancer patients (19 females) who received irinotecan at a BSA-normalized dose of 350 mg/m(2). RESULTS: The interindividual variability in irinotecan clearance (25.9% versus 25.1%; P = 0.93), in relative extent of conversion to SN-38 (47.8% versus 42.7%; P = 0.24), and in relative extent of SN-38 glucuronidation (71.2% versus 72.4%; P = 0.95) were not significantly different between the two dose groups. Variance differences in irinotecan-mediated hematological side effects were also similar between the 600 mg and 350 mg/m(2) groups (P > 0.14). CONCLUSIONS: These findings suggest that flat-fixed dosing of irinotecan does not result in increased pharmacokinetic/pharmacodynamic variability and could be safely used to supplant current dosing strategies based on BSA