Phase II NCCTG trial of RT + irinotecan and adjuvant BCNU plus irinotecan for newly diagnosed GBM

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

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Irinotecan has radiosensitizing effects and shows synergism with nitrosoureas. We performed a Phase II study of RT and irinotecan, followed by BCNU plus irinotecan in newly-diagnosed GBM. The MTD for patients receiving enzyme-inducing anticonvulsants (EIAC) was as follows: irinotecan 400 mg/m 2/week on Days 1, 8, 22 and 29 during RT, followed by BCNU 100 mg/m2 Day 1, and irinotecan, 400 mg/m2 on Days 1, 8, 22 and 29, every 6 weeks. The MTD for non-EIAC patients was as follows: irinotecan 125 mg/m2/week on Days 1, 8, 22 and 29 during RT, followed by BCNU 100 mg/m2 Day 1 and irinotecan 75 mg/m2 Days 1, 8, 22 and 29, every 6 weeks. Median OS was 10.8 mos. (95% CI: 7.7-14.9); OS at 12 months was 44.6% (95% CI: 33.3-59.8) and PFS 6 was 28.6% (95% CI: 18.9-43.2). Patients went off treatment due to adverse events (7%), refusal (11%), progressive disease (48%), death (9%), and other (9%); 16% completed protocol treatment. Survival was similar in patients with variant (6/7 or 7/7) and wild-type (6/6) UGT1A1*28 genotypic alleles. Grade 3-4 toxicity was more common in non-EIAC patients with variant alleles. SN-38 Cmax and AUC in EIAC patients receiving 400 mg/m2 irinotecan were 20.9 ng/ml and 212 ng/ml h, and in non-EIAC patients receiving 125 mg/m2, 15.5 ng/ml and 207 ng/ml h. SN-38 AUC varied by UGT1A1*28 status in non-EIAC patients. This regimen was not significantly active and radiosensitization was not observed. Non-EIAC patients with UGT1A1*28 variant alleles appear particularly sensitive to toxicity from irinotecan.

Original languageEnglish (US)
Pages (from-to)73-80
Number of pages8
JournalJournal of neuro-oncology
Volume99
Issue number1
DOIs
StatePublished - Aug 1 2010

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Keywords

  • BCNU
  • Enzyme-inducing anticonvulsant
  • Glioblastoma
  • Irinotecan
  • NCCTG
  • Nitrosourea
  • UGT1A1

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Cite this

Jaeckle, K. A., Ballman, K. V., Giannini, C., Schomberg, P. J., Ames, M. M., Reid, J. M., McGovern, R. M., Safgren, S. L., Galanis, E., Uhm, J. H., Brown, P. D., Hammack, J. E., Arusell, R., Nikcevich, D. A., Morton, R. F., Wender, D. B., & Buckner, J. C. (2010). Phase II NCCTG trial of RT + irinotecan and adjuvant BCNU plus irinotecan for newly diagnosed GBM. Journal of neuro-oncology, 99(1), 73-80. https://doi.org/10.1007/s11060-009-0103-2