PURPOSE: To further evaluate the activity of irinotecan (CPT-11) plus 1,3-bis-(chloroethyl)-1-nitrosourea (BCNU) in the treatment of central nervous system tumor-derived xenografts in athymic nude mice. METHODS: We report studies evaluating the schedule-dependence of this regimen in the treatment of the malignant glioma xenograft D-54 MG. RESULTS: The combination of BCNU and CPT-11 showed the highest enhancement index (2.0-3.3) when BCNU was given on day 1 and CPT-11 was given on days 1-5 and 8-12. Delay of CPT-11 administration to day 3 or day 5 substantially decreased activity with enhancement indices of 1.6-1.8 and 0.6-1.0, respectively. Delay of BCNU administration to day 8 also reduced the CPT-11 activity with enhancement indices of 1.2-1.4. CONCLUSIONS: These results suggest that the presence of a BCNU-induced adduct or possibly crosslink prior to administration of CPT-11 is critical for enhanced activity. Although the mechanism of this enhancement is not currently known, a phase I trial of CPT-11 plus BCNU for adults with recurrent malignant glioma based on these results is in progress.
PURPOSE: To further evaluate the activity of irinotecan (CPT-11) plus 1,3-bis-(chloroethyl)-1-nitrosourea (BCNU) in the treatment of central nervous system tumor-derived xenografts in athymic nude mice. METHODS: We report studies evaluating the schedule-dependence of this regimen in the treatment of the malignant glioma xenograft D-54 MG. RESULTS: The combination of BCNU and CPT-11 showed the highest enhancement index (2.0-3.3) when BCNU was given on day 1 and CPT-11 was given on days 1-5 and 8-12. Delay of CPT-11 administration to day 3 or day 5 substantially decreased activity with enhancement indices of 1.6-1.8 and 0.6-1.0, respectively. Delay of BCNU administration to day 8 also reduced the CPT-11 activity with enhancement indices of 1.2-1.4. CONCLUSIONS: These results suggest that the presence of a BCNU-induced adduct or possibly crosslink prior to administration of CPT-11 is critical for enhanced activity. Although the mechanism of this enhancement is not currently known, a phase I trial of CPT-11 plus BCNU for adults with recurrent malignant glioma based on these results is in progress.
Authors: David A Reardon; Annick Desjardins; Katherine B Peters; Sridharan Gururangan; John H Sampson; Roger E McLendon; James E Herndon; Anuradha Bulusu; Stevie Threatt; Allan H Friedman; James J Vredenburgh; Henry S Friedman Journal: J Neurooncol Date: 2011-10-11 Impact factor: 4.130
Authors: W Cai; N V Maldonado; W Cui; N Harutyunyan; L Ji; R Sposto; C P Reynolds; N Keshelava Journal: Br J Cancer Date: 2010-10-05 Impact factor: 7.640
Authors: Jennifer A Quinn; David A Reardon; Allan H Friedman; Jeremy N Rich; John H Sampson; James Vredenburgh; Sridharan Gururangan; James M Provenzale; Amy Walker; Holly Schweitzer; Darell D Bigner; Sandra Tourt-Uhlig; James E Herndon; Mary Lou Affronti; Susanne Jackson; Deborah Allen; Karen Ziegler; Cindy Bohlin; Christy Lentz; Henry S Friedman Journal: Neuro Oncol Date: 2004-04 Impact factor: 12.300
Authors: David A Reardon; Jennifer A Quinn; Jeremy N Rich; Sridharan Gururangan; James Vredenburgh; John H Sampson; James M Provenzale; Amy Walker; Michael Badruddoja; Sandra Tourt-Uhlig; James E Herndon; Jeannette M Dowell; Mary Lou Affronti; Susanne Jackson; Deborah Allen; Karen Ziegler; Steven Silverman; Cindy Bohlin; Allan H Friedman; Darell D Bigner; Henry S Friedman Journal: Neuro Oncol Date: 2004-04 Impact factor: 12.300
Authors: Kurt A Jaeckle; Karla V Ballman; Caterina Giannini; Paula J Schomberg; Matthew M Ames; Joel M Reid; Renee M McGovern; Stephanie L Safgren; Evanthia Galanis; Joon H Uhm; Paul D Brown; Julie E Hammack; Robert Arusell; Daniel A Nikcevich; Roscoe F Morton; Donald B Wender; Jan C Buckner Journal: J Neurooncol Date: 2010-01-09 Impact factor: 4.130
Authors: R C Cornelison; J X Yuan; K M Tate; A Petrosky; G F Beeghly; M Bloomfield; S C Schwager; A L Berr; C A Stine; D Cimini; F F Bafakih; J W Mandell; B W Purow; B J Horton; J M Munson Journal: NPJ Precis Oncol Date: 2022-07-29