title: Erlotinib 'dosing-to-rash': a phase II intrapatient dose escalation and pharmacologic study of erlotinib in previously treated advanced non-small cell lung cancer.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: 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
authors: A C
authors: AC
authors: Mita
authors: K
authors: K
authors: Papadopoulos
authors: M J A
authors: MJ
authors: de Jonge
authors: G
authors: G
authors: Schwartz
authors: J
authors: J
authors: Verweij
authors: M M
authors: MM
authors: Mita
authors: A
authors: A
authors: Ricart
authors: Q S-C
authors: QS
authors: Chu
authors: A W
authors: AW
authors: Tolcher
authors: L
authors: L
authors: Wood
authors: S
authors: S
authors: McCarthy
authors: M
authors: M
authors: Hamilton
authors: K
authors: K
authors: Iwata
authors: B
authors: B
authors: Wacker
authors: K
authors: K
authors: Witt
authors: E K
authors: EK
authors: Rowinsky
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D000069347:Erlotinib Hydrochloride; D005076:Exanthema / Q000139:chemically induced*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011799:Quinazolines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride