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

Mita, A C; Papadopoulos, K; de Jonge, M J A; Schwartz, G; Verweij, J; Mita, M M; Ricart, A; Chu, Q S-C; Tolcher, A W; Wood, L; McCarthy, S; Hamilton, M; Iwata, K; Wacker, B; Witt, K; Rowinsky, E K

<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>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.

SMALL cell lung cancer; ANTINEOPLASTIC agents; EPIDERMAL growth factor; PHARMACOKINETICS; PHARMACODYNAMICS; LUNG cancer

British Journal of Cancer, 2011, Vol 105, Issue 7, p938

0007-0920

Academic Journal

10.1038/bjc.2011.332