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

Kurt 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

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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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irinotecan
Carmustine
Anticonvulsants
Alleles
Area Under Curve
Radiation-Sensitizing Agents

All Science Journal Classification (ASJC) codes

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Cite this

Jaeckle, K., Ballman, K. V., Giannini, C., Schomberg, P. J., Ames, M. M., Reid, J. M., ... 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
Jaeckle, Kurt ; Ballman, Karla V. ; Giannini, Caterina ; Schomberg, Paula J. ; Ames, Matthew M. ; Reid, Joel M. ; McGovern, Renee M. ; Safgren, Stephanie L. ; Galanis, Evanthia ; Uhm, Joon H. ; Brown, Paul D. ; Hammack, Julie E. ; Arusell, Robert ; Nikcevich, Daniel A. ; Morton, Roscoe F. ; Wender, Donald B. ; Buckner, Jan C. / Phase II NCCTG trial of RT + irinotecan and adjuvant BCNU plus irinotecan for newly diagnosed GBM. In: Journal of Neuro-Oncology. 2010 ; Vol. 99, No. 1. pp. 73-80.
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title = "Phase II NCCTG trial of RT + irinotecan and adjuvant BCNU plus irinotecan for newly diagnosed GBM",
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.",
author = "Kurt Jaeckle and Ballman, {Karla V.} and Caterina Giannini and Schomberg, {Paula J.} and Ames, {Matthew M.} and Reid, {Joel M.} and McGovern, {Renee M.} and Safgren, {Stephanie L.} and Evanthia Galanis and Uhm, {Joon H.} and Brown, {Paul D.} and Hammack, {Julie E.} and Robert Arusell and Nikcevich, {Daniel A.} and Morton, {Roscoe F.} and Wender, {Donald B.} and Buckner, {Jan C.}",
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Jaeckle, K, Ballman, KV, Giannini, C, Schomberg, PJ, Ames, MM, Reid, JM, McGovern, RM, Safgren, SL, Galanis, E, Uhm, JH, Brown, PD, Hammack, JE, Arusell, R, Nikcevich, DA, Morton, RF, Wender, DB & Buckner, JC 2010, 'Phase II NCCTG trial of RT + irinotecan and adjuvant BCNU plus irinotecan for newly diagnosed GBM', Journal of Neuro-Oncology, vol. 99, no. 1, pp. 73-80. https://doi.org/10.1007/s11060-009-0103-2

Phase II NCCTG trial of RT + irinotecan and adjuvant BCNU plus irinotecan for newly diagnosed GBM. / Jaeckle, Kurt; Ballman, Karla V.; Giannini, Caterina; Schomberg, Paula J.; Ames, Matthew M.; Reid, Joel M.; McGovern, Renee M.; Safgren, Stephanie L.; Galanis, Evanthia; Uhm, Joon H.; Brown, Paul D.; Hammack, Julie E.; Arusell, Robert; Nikcevich, Daniel A.; Morton, Roscoe F.; Wender, Donald B.; Buckner, Jan C.

In: Journal of Neuro-Oncology, Vol. 99, No. 1, 01.08.2010, p. 73-80.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase II NCCTG trial of RT + irinotecan and adjuvant BCNU plus irinotecan for newly diagnosed GBM

AU - Jaeckle, Kurt

AU - Ballman, Karla V.

AU - Giannini, Caterina

AU - Schomberg, Paula J.

AU - Ames, Matthew M.

AU - Reid, Joel M.

AU - McGovern, Renee M.

AU - Safgren, Stephanie L.

AU - Galanis, Evanthia

AU - Uhm, Joon H.

AU - Brown, Paul D.

AU - Hammack, Julie E.

AU - Arusell, Robert

AU - Nikcevich, Daniel A.

AU - Morton, Roscoe F.

AU - Wender, Donald B.

AU - Buckner, Jan C.

PY - 2010/8/1

Y1 - 2010/8/1

N2 - 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.

AB - 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.

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