Overcoming CYP1A1/1A2 mediated induction of metabolism by escalating erlotinib dose in current smokers.

Purpose: Cigarette smoking induces CYP1A1/1A2 and is hypothesized to alter erlotinib pharmacokinetics. This study aimed to determine the maximum tolerated dose (MTD) of erlotinib in advanced non-small-cell lung cancer (NSCLC) patients who smoke and compare the pharmacokinetics of erlotinib at the MTD in current smokers with 150 mg.

Patients And Methods: Cohorts of NSCLC patients currently smoking > or = 10 cigarettes per day for > or = 1 year received escalating doses of erlotinib for 14 days until dose-limiting toxicity (DLT).

Retreatment with pemetrexed-based chemotherapy in malignant pleural mesothelioma (MPM): a second line treatment option.

The role of second line treatment in malignant pleural mesothelioma (MPM) is currently undefined. We present four cases of patients who had durable responses from pemetrexed-based chemotherapy who were retreated with a similar regimen upon progression of their mesothelioma. This case series explores the possible role of retreatment with pemetrexed-based chemotherapy as a second line therapeutic option in MPM.

2-[11C]thymidine positron emission tomography as an indicator of thymidylate synthase inhibition in patients treated with AG337.

Background: Some anticancer drugs inhibit thymidylate synthase (TS), a key enzyme for thymidine nucleotide biosynthesis. Cells can compensate for depleted thymidine levels by taking up extracellular thymidine via a salvage pathway. We investigated the use of 2-[11C]thymidine positron emission tomography (PET) to measure thymidine salvage kinetics in vivo in humans.