Erlotinib 'dosing-to-rash': a phase II intrapatient dose escalation and pharmacologic study of erlotinib in previously treated advanced non-small cell lung cancer

AC Mita, K Papadopoulos, Maja de Jonge, G Schwartz, Jaap Verweij, MM Mita, A Ricart, QC Chu, AW Tolcher, L Wood, S McCarthy, M Hamilton, K Iwata, B Wacker, K Witt, EK Rowinsky

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BACKGROUND: To evaluate the anticancer activity of erlotinib in patients with previously treated, advanced non-small cell lung cancer (NSCLC) whose dose is increased to that associated with a maximal level of tolerable skin toxicity (i.e., target rash (TR)); to characterise the pharmacokinetics (PK) and pharmacodynamics (PD) of higher doses of erlotinib. METHODS: Patients initially received erlotinib 150 mg per day. The dose was successively increased in each patient to that associated with a TR. Anticancer activity was evaluated. Plasma, skin, and hair were sampled for PK and PD studies. RESULTS: Erlotinib dose escalation to 200-475 mg per day was feasible in 38 (90%) of 42 patients. Twenty-four (57%) patients developed a TR, but 19 (79%) did so at 150 mg per day. Five (12%) patients, all of whom developed a TR, had a partial response. Median progression-free survival (PFS) was 2.3 months (95% CI: 1.61, 4.14); median PFS was 3.5 months and 1.9 months, respectively, for patients who did and did not experience a TR (hazard ratio, 0.51; P = 0.051). Neither rash severity nor response correlated with erlotinib exposure. CONCLUSION: Intrapatient dose escalation of erlotinib does not appreciably increase the propensity to experience a maximal level of tolerable skin toxicity, or appear to increase the anticancer activity of erlotinib in NSCLC. British Journal of Cancer (2011) 105, 938-944. doi:10.1038/bjc.2011.332 Published online 30 August 2011 (C) 2011 Cancer Research UK
Original languageUndefined/Unknown
Pages (from-to)938-944
Number of pages7
JournalBritish Journal of Cancer
Issue number7
Publication statusPublished - 2011

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  • EMC MM-03-86-08

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