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Investigational New Drugs

, Volume 24, Issue 3, pp 177–180 | Cite as

Pre-irradiation 9-Amino [20s] camptothecin (9-AC) in patients with newly diagnosed glioblastoma multiforme

  • Daniel Farray
  • Manmeet S. Ahluwalia
  • Josette Snyder
  • Gene H. Barnett
  • Bruce H. Cohen
  • John H. Suh
  • David M. PeereboomEmail author
Preclinical Studies

Summary

Purpose: To evaluate the efficacy of 9-amino [20s] camptothecin (9-AC) given before radiation therapy to patients with newly diagnosed glioblastoma multiforme (GBM). Methods: Eligible patients had newly diagnosed GBM who had residual measurable contrast-enhancing tumor. The trial was a phase 2 trial of 9-AC at 1100 μg/m2 /24 h infused over 72 h every two weeks for up to six cycles in patients with newly diagnosed GBM before radiation therapy. Results: Fourteen patients entered the study and all were evaluable. All of the patients had progressive disease by imaging criteria after at least two cycles of 9-AC (1 month). The median overall survival was 7.5 months (range 1.5–18 months). The most common adverse event was transient lymphopenia (grade 3–4). One patient developed grade 4 neutropenic fever that resolved after three days of diagnosis. Conclusions: 9-AC lacks activity against glioblastoma multiforme (GBM). Further studies looking at the efficacy of 9-AC in GBM may be futile.

Key Words

camptothecin glioblastoma multiforme high grade astrocytomas chemotherapy 

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References

  1. 1.
    Greenlee RT, Murray T, Bolden S, Wingo PA: Cancer statistics. CA Cancer J Clin 50(1): 7, 2000PubMedGoogle Scholar
  2. 2.
    Stupp R, Mason WP, Van Der Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10): 987–996, 2005Google Scholar
  3. 3.
    Rubin E, Wood V, Bharti A, Trites D, Lynch C, Hurwitz S, Bartel S, Levy S, Rosowsky A, Toppmeyer D, et al: A phase I and pharmacokinetic study of a new camptothecin derivative, 9-aminocamptothecin. Clin Cancer Res 1(3): 269, 1995PubMedGoogle Scholar
  4. 4.
    Wang JC: DNA topoisomerases. Annu Rev Biochem 54: 665–697, 1985 (Review)CrossRefPubMedGoogle Scholar
  5. 5.
    Hsiang Y, Hertyzberg R, Hecht S, Liu LF: Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I.J Biol Chem 260(27): 14873–14878, 1985Google Scholar
  6. 6.
    Hertzberg RP, Carafana MJ, Hecht SM: On the mechanism of topoisomerase I inhibition by camptothecin: Evidence for binding to an enzyme-DNA complex. Biochemistry 28(11): 4629–4638, 1989Google Scholar
  7. 7.
    Giovanella BC, Stehlin JS, Wall ME, Wani MC, Nicholas AW, Liu LF, Silber R, Potmesil M: DNA topoisomerase I–targeted chemotherapy of human colon cancer in xenografts. Science 246(4933): 1046–1048, 1989Google Scholar
  8. 8.
    Pantazis P, Hinz HR, Mendoza JT, Kozielski AJ, Williams LJ Jr, Stehlin JS Jr, Giovanella BC: Complete inhibition of growth followed by death of human malignant melanoma cells in vitro and regression of human melanoma xenografts in immunodeficient mice induced by camptothecins. Cancer Res 52(14): 3980–3987, 1992Google Scholar
  9. 9.
    Dahut W, Harold N, Takimoto C, Allegra C, Chen A, Hamilton JM, Arbuck S, Sorensen M, Grollman F, Nakashima H, Lieberman R, Liang M, Corse W, Grem J: Phase I and pharmacologic study of 9-aminocamptothecin given by 72-hour infusion in adult cancer patients. J Clin Oncol 14(4): 1236, 1996PubMedGoogle Scholar
  10. 10.
    Dancey J, Eisenhauer EA: Current perspectives on camptothecins in cancer treatment. Br J Cancer 74(3): 327, 1996PubMedGoogle Scholar
  11. 11.
    Hochberg F, Grossman SA, Mikkelsen T, Glantz M, Fisher JD, Piantadosi S: Lack of efficacy of 9-aminocamptothecin in adults with newly diagnosed glioblastoma multiforme and recurrent high-grade astrocytoma. NABTT CNS Consortium. Neuro-Oncol 2(1): 29, 2000CrossRefPubMedGoogle Scholar
  12. 12.
    Grossman SA, Fisher JD, Piantadosi, Brem H: The new approaches to brain tumor therapy (NABTT) CNS consortium: Organization, objectives, and activities. Cancer Control 5: 107–114, 1998PubMedGoogle Scholar
  13. 13.
    Friedman HS, Petros WP, Friedman AH et al: Irinotecan therapy in adults with recurrent or progressive malignant glioma. Journal of Clinical Oncology 17(5): 1516–1525, 1999Google Scholar
  14. 14.
    Gruber ML, Buster WP: Temozolomide in combination with irinotecan for treatment of recurrent malignant glioma. Am J Clin Oncol 27(1): 33–38 2004Google Scholar
  15. 15.
    Crews KR, Stewart CF, Jones-Wallace D, Thompson SJ, Houghton PJ, Heideman RL, Fouladi M, Bowers DC, Chintagumpala MM, Gajjar A: Altered irinotecan pharmacokinetics in pediatric high-grade glioma patients receiving enzyme-inducing anticonvulsant therapy. Clin Cancer Res 8(7): 2202–2209, 2002Google Scholar
  16. 16.
    Macdonald D, Cairncross G, Stewart D, Forsyth P, Sawka C, Wainman N, Eisenhauer E: Phase II study of topotecan in patients with recurrent malignant glioma. National clinical Institute of Canada Clinical Trials Group. Ann Oncol 7(2): 205–207, 1996Google Scholar
  17. 17.
    Burch PA, Bernath AM, Cascino TL et al: A north central cancer treatment group phase II trial of topotecan in relapsed gliomas. Invest New Drugs 18(3): 275–280, 2000CrossRefPubMedGoogle Scholar
  18. 18.
    Friedman HS, Kerby T, Fields S et al: Topotecan treatment of adults with primary malignant glioma. The brain tumor center at duke. Cancer 85(5): 1160–1165, 1999CrossRefGoogle Scholar
  19. 19.
    Keir ST, Hausheer F, Lawless AA, Bigner DD, Friedman HS: Therapeutic activity of 7-[(2-trimethylsilyl)ethyl]-20 (S)-Camptothecin against central nervous tumor-derived xenografts in athymic mice. Cancer Chemother Pharmcol 48(1): 83–87, 2001CrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2005

Authors and Affiliations

  • Daniel Farray
    • 1
  • Manmeet S. Ahluwalia
    • 2
  • Josette Snyder
    • 3
  • Gene H. Barnett
    • 3
  • Bruce H. Cohen
    • 3
  • John H. Suh
    • 3
  • David M. Peereboom
    • 3
    Email author
  1. 1.Loyola University Medical CenterMaywood
  2. 2.Roswell Park Cancer CenterBuffalo
  3. 3.Cleveland Clinic Brain Tumor InstituteCleveland

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