We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Phase I and pharmacokinetic study of irinotecan in combination with raltitrexed.
- Authors
Lewis, Nancy L.; Scher, Richard; Gallo, James M.; Engstrom, Paul F.; Szarka, Christine E.; Litwin, Samuel; Adams, Andrea L.; Kilpatrick, Deborah; Brady, Diane; Weiner, Louis M.; Meropol, Neal J.
- Abstract
<bold>Purpose: </bold>To determine the maximum tolerated dose (MTD) of raltitrexed when given with irinotecan and to evaluate the pharmacokinetics of these two agents when given in combination.<bold>Methods: </bold>Patients with advanced solid tumors received irinotecan intravenously over 90 min on days 1 and 8 of each 21-day cycle, with raltitrexed given intravenously over 15 min after irinotecan either on day 1 (cohorts 1-7) or day 2 (cohorts 8-9). The 39 patients received irinotecan and raltitrexed in cohorts of three to six patients at the following dose levels (mg/m(2)): 100/1.0, 100/1.5, 100/2.0, 100/2.5, 100/3.0, 100/3.5, 125/3.0, 75/3.0, 100/3.0. Pharmacologic monitoring of irinotecan and raltitrexed was carried out during cycle 1.<bold>Results: </bold>A total of 39 patients received irinotecan and raltitrexed in cohorts of three to six patients at nine dose levels. The MTD with dosing of irinotecan on days 1 and 8 and raltitrexed on day 1 was 100 mg/m(2) and 3.0 mg/m(2), respectively, every 21 days, with dose-limiting toxicities (DLTs) of fatigue, neutropenia and diarrhea. When raltitrexed was administered 24 h after irinotecan, these doses exceeded the MTD. No pharmacologic interactions were observed between these agents, and no correlations between pharmacokinetic parameters and toxicity were noted. Of 26 patients with colorectal cancer, 6 had objective partial responses (23%). Four of these patients had previously received a 5-FU-based regimen, two for metastatic disease.<bold>Conclusions: </bold>Irinotecan can be safely administered with raltitrexed on a day-1 and day-8 schedule at 100 mg/m(2) and 3.0 mg/m(2), respectively, every 21 days. When raltitrexed was given on day 2, these doses were not tolerated, necessitating a dose reduction of the irinotecan to 75 mg/m(2). This regimen possesses clinical activity in patients with colorectal cancer.
- Subjects
CANCER patients; COLON cancer; DRUG metabolism; CHEMICAL kinetics; INTESTINAL diseases; CHEMICAL affinity
- Publication
Cancer Chemotherapy & Pharmacology, 2002, Vol 50, Issue 4, p257
- ISSN
0344-5704
- Publication type
journal article
- DOI
10.1007/s00280-002-0500-0