Purpose: We conducted a phase I trial of irinotecan (CPT-11), a topoisomerase I inhibitor, combined with amrubicin, a topoisomerase II inhibitor, with recombinant human granulocyte colony-stimulating factor (rhG-CSF) support to overcome the neutropenia associated with this particular combination. The aim was to determine the maximum tolerated dose (MTD) of amrubicin combined with a fixed dose of CPT-11 and the dose-limiting toxicities (DLTs) of this combination in extensive-stage small-cell lung cancer (ED-SCLC) patients.
Methods: Fifteen patients with ED-SCLC were treated at 3-week intervals with amrubicin on days 1-3 plus 60 mg/m(2) CPT-11 on days 1 and 8. In addition, prophylactic rhG-CSF (50 μg/m(2)) was given from day 4 to day 21, except on the day of CPT-11 administration. Amrubicin was started at 30 mg/m(2) and then escalated in 5 mg/m(2) increments until MTD was reached.
Results: The MTD of amrubicin was 35 mg/m(2), since 2 of 4 patients experienced DLTs during the first cycle of treatment at the 40 mg/m(2) dose level. Neutropenia, neutropenic fever, ileus, and diarrhea were the DLTs. There were 13 partial responses among the 13 assessable patients, yielding an overall response rate of 100 %. Median progression-free survival and overall survival were 7.4 months and 13.4 months, respectively.
Conclusion: The combination of amrubicin and CPT-11 showed high activity against ED-SCLC with acceptable toxicity. Use of rhG-CSF allowed the dose of amrubicin to be raised 40 % above that in the original regimen (60 mg/m(2) CPT-11 and 25 mg/m(2) amrubicin).