OBJECTIVES:: Preclinical studies have demonstrated anticancer synergism with the combination of inhibitors of topoisomerases I and II. A population-based phase I trial was conducted to determine a population-based maximum tolerated dose (pMTD) for combining 2 topoisomerase inhibitors, irinotecan and epirubicin. METHODS:: Two cohorts of patients with advanced solid tumors were enrolled: 27 patients had and 22 patients had not received prior chemotherapy. In each cohort, irinotecan and epirubicin were administered beginning at a predetermined dose level. The dose for each subsequent 21-day cycle was escalated or de-escalated within each patient based on the dose-limiting toxicity observed in the previous cycle and according to a predetermined schema of dose levels. An MTD was determined for each patient (iMTD) and the iMTDs were used to determine a pMTD for each cohort of patients. RESULTS:: The most common dose-limiting toxicity included neutropenia (51%), asthenia (10%), diarrhea (8%), and nausea/emesis (4%). The iMTDs ranged from dose level -3 to dose level 6. For previously chemotherapy-treated patients, the pMTD was 100 mg/m of irinotecan and 50 mg/m of epirubicin. For chemonaive patients, the pMTD was 150 mg/m of irinotecan and 50 mg/m of epirubicin. CONCLUSIONS:: We have determined the pMTD of irinotecan and epirubicin administered every 3 weeks using a population-based approach. The pMTD is recommended for conducting phase II trials.
|Original language||English (US)|
|Number of pages||5|
|Journal||American Journal of Clinical Oncology: Cancer Clinical Trials|
|State||Published - Jun 2008|
- Population-based phase I trial
ASJC Scopus subject areas
- Cancer Research