Randomized phase II study of pulse erlotinib before or after carboplatin and paclitaxel in current or former smokers with advanced non-small-cell lung cancer Journal Article


Authors: Riely, G. J.; Rizvi, N. A.; Kris, M. G.; Milton, D. T.; Solit, D. B.; Rosen, N.; Senturk, E.; Azzoli, C. G.; Brahmer, J. R.; Sirotnak, F. M.; Seshan, V. E.; Fogle, M.; Ginsberg, M.; Miller, V. A.; Rudin, C. M.
Article Title: Randomized phase II study of pulse erlotinib before or after carboplatin and paclitaxel in current or former smokers with advanced non-small-cell lung cancer
Abstract: Purpose: A prior study demonstrated that addition of continuous daily erlotinib fails to improve response rate or survival in non-small-cell lung cancer (NSCLC) patients treated with carboplatin and paclitaxel. However, preclinical data support the hypothesis that intermittent administration of erlotinib before or after chemotherapy may improve efficacy. We tested this hypothesis in patients with advanced NSCLC. Patients and Methods: Eligible patients were former or current smokers with chemotherapy-naive stage IIIB or IV NSCLC. All patients received up to six cycles of carboplatin (area under the curve = 6) and paclitaxel (200 mg/m<sup>2</sup>), with random assignment to one of the following three erlotinib treatments: erlotinib 150 mg on days 1 and 2 with chemotherapy on day 3 (150 PRE); erlotinib 1,500 mg on days 1 and 2 with chemotherapy on day 3 (1,500 PRE); or chemotherapy on day 1 with erlotinib 1,500 mg on days 2 and 3 (1,500 POST). The primary end point was response rate. Results: Eighty-six patients received treatment. The response rates for the 150 PRE, 1,500 PRE, and 1,500 POST arms were 18% (five of 28 patients), 34% (10 of 29 patients), and 28% (eight of 29 patients), respectively. The median overall survival times were 10, 15, and 10 months for the 150 PRE, 1,500 PRE, and 1,500 POST arms, respectively. The most common grade 3 and 4 toxicities were neutropenia (39%), fatigue (15%), and anemia (12%). Grade 3 and 4 rash and diarrhea were uncommon. Conclusion: Patients treated on the 1,500 PRE arm had the highest response rate and longest survival, with ranges similar to those reported for carboplatin, paclitaxel, and bevacizumab in a more restricted population. Further evaluation of this strategy in a phase III trial is proposed. © 2008 by American Society of Clinical Oncology.
Keywords: adult; controlled study; treatment outcome; treatment response; aged; aged, 80 and over; middle aged; major clinical study; overall survival; genetics; clinical trial; fatigue; neutropenia; erlotinib; diarrhea; drug dose reduction; drug efficacy; paclitaxel; cancer staging; antineoplastic agent; neoplasm staging; carboplatin; controlled clinical trial; multiple cycle treatment; phase 2 clinical trial; anemia; lung non small cell cancer; mucosa inflammation; neuropathy; randomized controlled trial; thrombocytopenia; antineoplastic combined chemotherapy protocols; carcinoma, non-small-cell lung; lung neoplasms; drug administration schedule; epidermal growth factor receptor; smoking; receptor, epidermal growth factor; pathology; dyspnea; rash; syncope; lung tumor; thrombosis; hyperbilirubinemia; genes, ras; drug administration; quinazolines; oncogene ras; quinazoline derivative
Journal Title: Journal of Clinical Oncology
Volume: 27
Issue: 2
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2009-01-10
Start Page: 264
End Page: 270
Language: English
DOI: 10.1200/jco.2008.17.4656
PUBMED: 19047285
PROVIDER: scopus
PMCID: PMC2645610
DOI/URL:
Notes: --- - "Cited By (since 1996): 11" - "Export Date: 30 November 2010" - "CODEN: JCOND" - "Source: Scopus"
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MSK Authors
  1. Venkatraman Ennapadam Seshan
    285 Seshan
  2. Neal Rosen
    363 Rosen
  3. Michelle S Ginsberg
    158 Ginsberg
  4. David Solit
    431 Solit
  5. Christopher G Azzoli
    105 Azzoli
  6. Naiyer A Rizvi
    156 Rizvi
  7. Vincent Miller
    262 Miller
  8. Gregory J Riely
    344 Riely
  9. Mark Kris
    598 Kris
  10. Francis M Sirotnak
    115 Sirotnak