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

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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/m2/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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Authors and Affiliations

  1. Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL, 32224, USA

    Kurt A. Jaeckle

  2. Mayo Clinic Rochester, Rochester, MN, 55905, USA

    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 & Jan C. Buckner

  3. Meritcare Hospital CCOP, Fargo, ND, 58122, USA

    Robert Arusell

  4. Duluth CCOP, Duluth, MN, 55805, USA

    Daniel A. Nikcevich

  5. Iowa Oncology Research Association CCOP, Des Moines, IA, 50309-1014, USA

    Roscoe F. Morton

  6. Siouxland Hematology-Oncology Associates, Sioux City, IA, 51105, USA

    Donald B. Wender

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  1. Kurt A. Jaeckle
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  2. Karla V. Ballman
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  3. Caterina Giannini
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  4. Paula J. Schomberg
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  6. Joel M. Reid
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  9. Evanthia Galanis
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  17. Jan C. Buckner
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Corresponding author

Correspondence to Kurt A. Jaeckle.

Additional information

This study was conducted as a collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic and was supported in part by Public Health Service grants CA-25224, CA-37404, CA-35269, CA-35101, CA-35103, CA-35113, CA-35431, CA-35267, CA-52352, CA-37417, CA-63848, and by grants from Pharmacia and Upjohn.

The content is solely the responsibility of the authors and does not necessarily represent the views of the National Cancer Institute or the National Institute of Health.

Additional participating institutions include in Appendix.

Appendix

Appendix

Additional participating institutions include: Rapid City Regional Oncology Group, Rapid City, SD 59709 (Richard Tenglin, M.D.); Mayo Clinic Arizona, Scottsdale, AZ 85259 (Tom R. Fitch, M.D.); CentraCare Clinic, St. Cloud, MN 56301 (Donald Jurgens, M.D.); Illinois Oncology Research Assn. CCOP, Peoria, IL 61602 (John W. Kugler, M.D.); Cedar Rapids Oncology Project CCOP, Cedar Rapids, IA 52403 (Martin Wiesenfeld, M.D.); Michigan Cancer Research Consortium, Ann Arbor, MI 48106 (Philip J. Stella, M.D.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, MN 55416 (Patrick J. Flynn, M.D.); Sioux Community Cancer Consortium, Sioux Falls, SD 57105 (Loren K. Tschetter, M.D.); Wichita Community Clinical Oncology Program, Wichita, KS 67214-3882 (Shaker R. Dakhil, M.D.).

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Jaeckle, K.A., Ballman, K.V., Giannini, C. et al. Phase II NCCTG trial of RT + irinotecan and adjuvant BCNU plus irinotecan for newly diagnosed GBM. J Neurooncol 99, 73–80 (2010). https://doi.org/10.1007/s11060-009-0103-2

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