Phase I and pharmacokinetic (PK) study of irinotecan (CPT-11) and amrubicin (AMR) in non-small cell Lung Cancer (NSCLC)

Abstract

2070 Background: CPT-11 (topoisomerase I inhibitor) and AMR (topoisomerase II inhibitor) are active against several solid tumors including NSCLC. Based on the preclinical data, this phase I trial was conducted to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), anti-tumor activity, and PK assessments of this combination. Methods: Previously untreated patients (Pts) with stage IIIB/IV disease were treated with AMR iv, days 1–3 with a fixed dose of CPT-11 (60 mg/m2 iv, days 1 and 8) every 3 weeks (wks). The starting dose of AMR was 25 mg/m2. Three pts were treated at each dose level, with expansion to 6 pts in the event of DLT. Results: Eight pts were enrolled: 4 males, 4 females; median age was 61 years (range, 46–63). No pt had DLT at the first dose level. The MTD was reached at the second cohort (AMR 30 mg/m2): 3 DLTs were observed in 5 pts, which consisted of diarrhea (1 pt) and more than 1 wk delay for WBC recovery (2 pts). No significant interactions on the plasma pharmacokinetics between AMR, its active metabolite 13 OH-AMR, CPT-11, SN-38 and SN-38 glucuronide (G) were observed. There were 3 partial responses (37.5%). Conclusion: The recommended dose with this schedule is 60 mg/m2 of CPT-11, days 1 and 8, and 25 mg/m2 of AMR, days 1–3 every 3 wks. No significant financial relationships to disclose.