TY - JOUR
T1 - Erlotinib 'dosing-to-rash': a phase II intrapatient dose escalation and pharmacologic study of erlotinib in previously treated advanced non-small cell lung cancer
AU - Mita, AC
AU - Papadopoulos, K
AU - de Jonge, Maja
AU - Schwartz, G
AU - Verweij, Jaap
AU - Mita, MM
AU - Ricart, A
AU - Chu, QC
AU - Tolcher, AW
AU - Wood, L
AU - McCarthy, S
AU - Hamilton, M
AU - Iwata, K
AU - Wacker, B
AU - Witt, K
AU - Rowinsky, EK
PY - 2011
Y1 - 2011
N2 - 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 www.bjcancer.com Published online 30 August 2011 (C) 2011 Cancer Research UK
AB - 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 www.bjcancer.com Published online 30 August 2011 (C) 2011 Cancer Research UK
U2 - 10.1038/bjc.2011.332
DO - 10.1038/bjc.2011.332
M3 - Article
C2 - 21878940
SN - 0007-0920
VL - 105
SP - 938
EP - 944
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 7
ER -