Pilot trial of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib plus carboplatin and paclitaxel in patients with stage IIIB or IV non-small-cell lung cancer Journal Article


Authors: Miller, V. A.; Johnson, D. H.; Krug, L. M.; Pizzo, B.; Tyson, L.; Perez, W.; Krozely, P.; Sandler, A.; Carbone, D.; Heelan, R. T.; Kris, M. G.; Smith, R.; Ochs, J.
Article Title: Pilot trial of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib plus carboplatin and paclitaxel in patients with stage IIIB or IV non-small-cell lung cancer
Abstract: Purpose: Gefitinib is an oral agent that inhibits the tyrosine kinase of the epidermal growth factor receptor. In phase I trials gefitinib was well tolerated and antitumor activity was seen in pretreated non-small-cell lung cancer (NSCLC) patients. Preclinical studies indicated enhanced effects when gefitnib was added to carboplatin or paclitaxel. This pilot trial combined gefitinib with carboplatin and paclitaxel to define the toxicities of the combination and assess drug-drug interactions in untreated advanced NSCLC patients. Patients and Methods: Initially (part 1) patients were randomly assigned to receive intermittent gefitinib with cycle 1 or 2 of chemotherapy. Thereafter (part 2), the highest dose of gefitinib that was given without dose-limiting toxicity (DLT) from part 1 was administered continuously beginning with the first cycle of chemotherapy. Three sequentially enrolled cohorts received gefitinib 250 and 500 mg (intermittently) and 500 mg (continuously). Results: We treated 24 patients; nine patients with 250 mg and 15 patients with 500 mg (nine patients continuous). Two occurrences of DLT were observed. One patient (500 mg, part 1) developed grade 3 rash and another patient (part 2) developed prolonged neutropenia. Steady-state gefitinib levels did not affect exposure to chemotherapy. In a limited sample, chemotherapy modestly increased the gefitinib area under concentration-time curve at steady-state and minimum steady-state trough concentration. Partial responses were observed in five of 24 patients. The median survival was 8 months. Conclusion: The gefitinib with carboplatin and paclitaxel regimen was generally well tolerated and no unanticipated toxicities or clinically relevant pharmacokinetic interactions were observed. Both doses of gefitinib were believed to be safe for further study with chemotherapy. This regimen was thus tested in a completed randomized phase III trial. © 2003 by American Society of Clinical Oncology.
Keywords: epidermal growth factor; adult; cancer survival; clinical article; controlled study; treatment response; aged; middle aged; survival rate; clinical trial; disease course; mortality; neutropenia; advanced cancer; area under the curve; dose response; united states; paclitaxel; cancer staging; antineoplastic agent; carboplatin; controlled clinical trial; multiple cycle treatment; steady state; lung non small cell cancer; randomized controlled trial; antineoplastic combined chemotherapy protocols; carcinoma, non-small-cell lung; lung neoplasms; cohort analysis; pathology; dose-response relationship, drug; protein tyrosine kinase; rash; lung tumor; drug antagonism; pilot study; pilot projects; gefitinib; area under curve; protein-tyrosine kinases; drug blood level; quinazolines; quinazoline derivative; epidermal growth factor receptor kinase inhibitor; humans; human; male; female; priority journal; article
Journal Title: Journal of Clinical Oncology
Volume: 21
Issue: 11
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2003-06-01
Start Page: 2094
End Page: 2100
Language: English
DOI: 10.1200/jco.2003.12.008
PUBMED: 12775734
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 12 September 2014 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Lee M Krug
    211 Krug
  2. Vincent Miller
    263 Miller
  3. Mark Kris
    612 Kris
  4. Robert T Heelan
    85 Heelan
  5. Leslie Tyson
    55 Tyson
  6. Barbara Pizzo
    31 Pizzo
  7. Wendy Perez
    4 Perez