Phase I-II study of irinotecan (CPT-11) and gefitinib in patients (pts) with gefitinib failure for non-small cell lung cancer (NSCLC)

Abstract

19014 Background: Currently, there are no effective treatment options for NSCLC after failure of gefitinib. Pre-clinical studies demonstrated that gefitinib resistant NSCLC cells were more sensitive to CPT-11 than parental cells, and the combination of CPT-11 and gefitinib had a synergistic effect. We conducted a phase I-II study to evaluate the combination of CPT-11 and gefitinib as a therapeutic option in NSCLC patients with progressive disease after treatment with gefitinib. Methods: Eligibility criteria included histologically confirmed NSCLC, age 20–74 years, refractory to or relapsed after gefitinib, one or more prior chemotherapy regimens, ECOG performance status (PS) 0- 2, adequate organ function and informed consent. Pts were treated with CPT-11 on days 1 and 15 every 4 weeks, and daily gefitinib from day 2. The treatment was continued until disease progression. The Gefitinib dose was fixed at 250 mg. The starting dose of CPT-11 was 50 mg/m2, and then was escalated in different pts at 25 mg/m2 increments up to 150 mg/m2. Results: 25 pts were enrolled: Male/female =14/11; Median age = 60 (45–74); Histology, adeno/non-adeno= 23/2; PS 0–1/2= 19/6; Prior gefitinib response, PR/SD/PD = 19/2/4. Toxicities and efficacy for each dose level are shown in the table. Dose limiting toxicities were observed in only 2 pts at level 3, and the full dose of CPT-11 could be combined with the full dose of gefitinib. The disease control rate (DCR) and response rate (RR) for all 25 pts were 72.0% and 28.0%. For 10 pts at level 5, the DCR and RR were 80.0% and 60.0%. Conclusion: The combination of CPT-11 and gefitinib is highly effective and well tolerated in pts with gefitinib failure for NSCLC. Level CPT-11 (mg/m2) Gefitinib (mg) Number of Pts Total Grade 3/4 neutropenia Grade 3/4 diarrhea DLT PR SD 1 50 250 3 0 0 0 0 2 2 75 250 3 0 0 0 0 1 3 100 250 6 1 2 2 0 4 4 125 250 3 0 0 0 1 2 5 150 250 10 3 0 0 6 2 No significant financial relationships to disclose.