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• W2044952801 abstract "The anti-tumor activity of irinotecan (CPT-11), a DNA-topoisomerase I inhibitor, was evaluated in 5 advanced stage subcutaneous medulloblastoma xenografts in nude mice, using different schedules of administration. With a 5-day schedule, the highest i.v. dose tested (40 mg kg−1 day−1) induced complete regressions in all xenografts but 1, and delays in tumor growth always exceeded 30 days. Two xenografts, IGRM11 and IGRM33, were highly sensitive, and animals survived tumor-free beyond 120 days after treatment. CPT-11 clearly retained its anti-tumor activity at a lower dosage (27 mg kg−1 day−1). CPT-11 was significantly more active than cyclophosphamide, thiotepa and etoposide against the 3 xenografts evaluated. To study the schedule dependency of its anti-tumor activity, CPT-11 was given i.v. at the same total doses over the same period (33 days) using either a protracted or a sequential schedule in IGRM34-bearing mice. With a dose of 10 mg kg−1 day−1 given on days 0–4, days 7–11, days 21–25 and days 28–32 (total dose, 200 mg kg−1), 3 of 6 animals were tumor free on day 378. The same total dose given with a sequential schedule, i.e., 20 mg kg−1 day−1 on days 0–4 and days 28–32, failed to induce complete regression. The plasma pharmacokinetics of CPT-11 and SN-38 were studied in IGRM34-bearing animals after a single i.v. dose of 10 and 40 mg kg−1. The plasma clearance rate of CPT-11 was dose dependent. The ratio between the SN-38 and CPT-11 area under the curve in plasma was 0.4–0.65, i.e., significantly higher than that observed in humans at the maximum tolerated dose (0.01–0.05). Conversely, this ratio was 10-fold lower in tumor than in plasma. Clinical development of irinotecan is warranted in pediatric malignancies. Int. J. Cancer 73:156–163, 1997. © 1997 Wiley-Liss, Inc." @default.
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• W2044952801 date "1997-09-26" @default.
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• W2044952801 title "Potent therapeutic activity of irinotecan (CPT-11) and its schedule dependency in medulloblastoma xenografts in nude mice" @default.
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• W2044952801 doi "https://doi.org/10.1002/(sici)1097-0215(19970926)73:1<156::aid-ijc24>3.0.co;2-d" @default.
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