Although erlotinib is an approved second-line therapy for lung cancer, its management is complicated by side effects that get worse as the dose increases.
"Increased doses may lead to better outcomes, so we are trying to determine how high we can go with this agent without having to stop," said Lynsay Waller, M.D., a fellow at Wake Forest University, who presented her data at the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer, held here Jan. 11-14, 2010.
Waller and colleagues evaluated 25 patients and put them on a chemotherapy regimen that began with docetaxel, cisplatin and pegfilgrastim growth factor support. The researchers then started administering erlotinib at 150 mg daily for non-smokers and 300 mg daily for smokers. These doses were increased every two weeks until development of grade 2 toxicity, when the doses stabilized. If grade 3 toxicity emerged, the doses were cut back by 75 mg a day.
Doses reached as high as 525 mg for smokers and 225 mg for non-smokers, but by the end of the study most smokers had a maximum tolerated dose of 300 mg compared with 225 mg for non-smokers.
The most common reasons for discontinuation of therapy was grade 2 rash, grade 2 or grade 3 diarrhea or grade 3 dehydration.