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Medline ® Abstract for Reference 93

of 'Dosing of anticancer agents in adults'

93
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Erlotinib 'dosing-to-rash': a phase II intrapatient dose escalation and pharmacologic study of erlotinib in previously treated advanced non-small cell lung cancer.
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Mita AC, Papadopoulos K, de Jonge MJ, Schwartz G, Verweij J, Mita MM, Ricart A, Chu QS, Tolcher AW, Wood L, McCarthy S, Hamilton M, Iwata K, Wacker B, Witt K, Rowinsky EK
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Br J Cancer. 2011 Sep;105(7):938-44. Epub 2011 Aug 30.
 
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 aTR, 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.
AD
Institute for Drug Development, Cancer Therapy and Research Center, University of Texas Health Science Center, 4th Floor, 7979 Wurzbach Road, Zeller Building, San Antonio, TX 78229, USA. Alain.Mita@gmail.com
PMID