Gefitinib (ZD1839) combined with gemcitabine or vinorelbine as single-agent in elderly patients with advanced non-small cell lung cancer (NSCLC)

Abstract

7081 Background: The activity and tolerability of either gemcitabine or vinorelbine given with gefitinib ('Iressa', ZD1839), an Epidermal Growth Factor Receptor-Tyrosine Kinase inhibitor was evaluated in an Italian multicentre randomised non-comparative phase II study in elderly patients with chemo-naive stage IIIB/IV NSCLC using a Fleming's single stage method. Methods: Fiftynine patients aged >=70 with measurable disease were randomised to receive gefitinib (250 mg/die orally until progression) plus either vinorelbine (30 mg/m2 iv) (armA) or gemcitabine (1200 mg/m2 iv) (arm B) both given on days 1 and 8 every 21 days for 6 cycles. Primary end-point was the assessment of tumour response rate measured by RECIST criteria. Results: Main patients' characteristics are (Arm A/B): median age 72/74 yrs.; males 58%/80%; WHO PS 0–1: 96%/91%; squamous histology 17%/31%. Arm A was prematurely closed after 87,5% of 24 randomised patients with grade 3–4 adverse events (AEs), 72% grade 3–4 neutropenia and 3 deaths treatment-related (one sudden cardiac arrest, one grade IV neutropenia with septic shock and cerebral infarction, one grade IV diarrhea followed by cardiac arrest). Arm B completed the planned accrual. Preliminary efficacy data are as follows : Arm A : 1 CR, 3 PR, 7 SD, 6 PD, 7 NE; median duration of response 36 days, median TTPD 91 days, MST 371 days; % of patients alive at 6 months 63%; Arm B : 3 PR, 13 SD, 9 PD, 10 NE, median duration of response 139 days, median TTPD 94 days, MST 275 days, % of patients alive at 6 months 61%. In both arms the most commonest gefitinib-related AE was skin toxicity (mainly grade 1–2) . In the arm B grade 3–4 neutropenia was 11.4% and thrombocitopenia 8.6% (0% in the arm A).Asthenia grade 3–4 was 5.7 in the arm B and 12% in the arm A. Diarrhea grade 3–4 occurred in 12% in arm A and 5.7 in arm B. Conclusions: In elderly patients with advanced NSCLC vinorelbine plus gefitinib was active but toxicity was unacceptable while gemcitabine plus gefitinib was safe, and a remarkable percentage of patients achieved disease control. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly AstraZeneca; Eli Lilly Italian Research Council