Chronomodulation of topotecan or X-radiation treatment increases treatment efficacy without enhancing acute toxicity
- Department of Physics, Carleton University, Ottawa, ON (Canada)
- Centre for Cancer Therapeutics, Ottawa Regional Cancer Centre, Ottawa, ON (Canada)
- Department of Medical Physics, Ottawa Regional Cancer Centre, Ottawa, ON (Canada)
- Department of Physics, Carleton University, Ottawa, ON (Canada) and Centre for Cancer Therapeutics, Ottawa Regional Cancer Centre, Ottawa, ON (Canada)
Purpose: Topotecan (TPT), a camptothecin analog, is currently used to treat human ovarian and small-cell lung cancer and is in clinical trials for other tumor sites. However, it is unknown whether chronomodulation of TPT treatment is beneficial. We examined the effects of administering TPT or X-radiation (XR) alone at different times of the day or night. Methods: We treated mice bearing human colorectal tumor xenografts at four different times representing the early rest period (9 AM or 3 HALO [hours after light onset]), late rest period (3 PM or 9 HALO), early active period (9 PM or 15 HALO), and late active period (3 AM or 21 HALO) of the mice. We gave either TPT (12 mg/kg, injected i.p.) or XR (4 Gy, directed to the tumor) twice weekly on Days 0, 4, 7, 10 within 2 weeks. Results: Treatment with either TPT or XR at 3 AM demonstrated the greatest efficacy (measured by a tumor regrowth assay) without significantly increasing acute toxicity (assessed by a decrease in leukocyte counts or body weight). Conversely, treatment at 3 PM, in particular, showed increased toxicity without any enhanced efficacy. Conclusions: Our study provided the first evidence that chronomodulation of TPT treatments, consistent with the findings of other camptothecin analogs, is potentially clinically beneficial. Additionally, our findings suggest that chronomodulation of fractionated XR treatments is also potentially clinically beneficial.
- OSTI ID:
- 20698432
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 62, Issue 1; Other Information: DOI: 10.1016/j.ijrobp.2004.12.084; PII: S0360-3016(05)00142-2; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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