This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Buckner, J. C. Articles by Jenkins, R. Search for Related Content PubMed PubMed Citation Articles by Buckner, J. C. Articles by Jenkins, R. Social Bookmarking                            What's this?

Phase II Trial of Procarbazine, Lomustine, and Vincristine as Initial Therapy for Patients With Low-Grade Oligodendroglioma or Oligoastrocytoma: Efficacy and Associations With Chromosomal Abnormalities

Jan C. Buckner, Dean Gesme, Jr, Judith R. O’Fallon, Julie E. Hammack, Scott Stafford, Paul D. Brown, Roland Hawkins, Bernd W. Scheithauer, Bradley J. Erickson, Ralph Levitt, Edward G. Shaw, Robert Jenkins

From the Mayo Clinic and Mayo Foundation, Rochester, MN; Cedar Rapids Oncology Project CCOP, Cedar Rapids, IA; Ochsner CCOP, New Orleans, LA; Meritcare Hospital CCOP, Fargo, ND; Wake Forest University, Winston-Salem, NC.

Address reprint requests to Jan C. Buckner, MD, Mayo Clinic, 200 First Street SW, Rochester, MN 55905; email: buckner.jan{at}mayo.edu.

Purpose: The purpose of this article is to determine the response rate and toxicity of PCV administered before radiation therapy in patients with newly diagnosed LGO/LGOA and to explore correlations between response with 1p/19q deletions and aberrant p53 expression.

Background: Despite prolonged survival of patients with low-grade oligodendroglioma (LGO) and oligoastrocytoma (LGOA), the majority will succumb to progressive disease. Because procarbazine, lomustine (CCNU), and vincristine (PCV) is active in patients with recurrent LGO/LGOA, we hypothesized that it would be beneficial as primary therapy.

Methods: Adult patients with residual tumor on magnetic resonance imaging scan following biopsy or subtotal resection of LGO/LGOA received up to six cycles of PCV. Radiation therapy (59.4 or 54.0 Gy) began within 10 weeks of completing chemotherapy or immediately if there was evidence of tumor progression on PCV. Tumor tissue was analyzed by fluorescent in situ hybridization for 1p and 19q deletion and by immunohistochemistry for p53 expression.

Results: Eight of 28 (29%) and 13 of 25 (52%) eligible patients demonstrated tumor regression as assessed by the treating physician and a blinded central neuroradiology reviewer, respectively. Myelosuppression was the predominant toxicity. Loss of 1p and 19q were associated with LGO but not LGOA (P = .009), were inversely associated with p53 detection, and were not associated with response to PCV (possibly because of the small sample size).

Conclusion: PCV produces tumor regressions in a meaningful proportion of patients with LGO/LGOA. Toxicity, especially myelosuppression, is significant. Loss of 1p and 19q seems limited to patients with pure LGO and is inversely related to p53 alterations.

This study was conducted as a collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic

Supported in part by Public Health Service grants CA-15083, CA-25224, CA-37404, CA-35101, CA-52352, CA-35195, CA-37417, CA-35448, CA-63848, and CA-50905 from the National Cancer Institute, Department of Health and Human Services, Bethesda, MD, and the Linse-Bock Foundation.

None of the authors has a financial conflict of interest concerning the agents used in this study.

Additional participating institutions include Iowa Oncology Research Association CCOP, Des Moines, IA (Roscoe F. Morton, MD); Geisinger Clinic and Medical Center CCOP, Danville, PA (Suresh Nair, MD); Altru Health Systems, Grand Forks, ND (Daniel J. Walsh, MD); Ann Arbor Regional CCOP, Ann Arbor, MI (Philip J. Stella, MD).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				J. E. C. Bromberg and M. J. van den Bent Oligodendrogliomas: Molecular Biology and Treatment Oncologist, February 1, 2009; 14(2): 155 - 163. [Abstract] [Full Text] [PDF]

				S. Kesari, D. Schiff, J. Drappatz, D. LaFrankie, L. Doherty, E. A. Macklin, A. Muzikansky, S. Santagata, K. L. Ligon, A. D. Norden, et al. Phase II Study of Protracted Daily Temozolomide for Low-Grade Gliomas in Adults Clin. Cancer Res., January 1, 2009; 15(1): 330 - 337. [Abstract] [Full Text] [PDF]

				W. P. Mason and J. G. Cairncross Invited Article: The expanding impact of molecular biology on the diagnosis and treatment of gliomas Neurology, July 29, 2008; 71(5): 365 - 373. [Abstract] [Full Text] [PDF]

				J. C. Buckner, P. D. Brown, B. P. O'Neill, F. B. Meyer, C. J. Wetmore, and J. H. Uhm Central Nervous System Tumors Mayo Clin. Proc., October 1, 2007; 82(10): 1271 - 1286. [Abstract] [Full Text] [PDF]

				D. Schiff, P. D. Brown, and C. Giannini Outcome in adult low-grade glioma: The impact of prognostic factors and treatment Neurology, September 25, 2007; 69(13): 1366 - 1373. [Abstract] [Full Text] [PDF]

				P. Y. Wen and L. M. DeAngelis Chemotherapy for low-grade gliomas: Emerging consensus on its benefits Neurology, May 22, 2007; 68(21): 1762 - 1763. [Full Text] [PDF]

				G. Kaloshi, A. Benouaich-Amiel, F. Diakite, S. Taillibert, J. Lejeune, F. Laigle-Donadey, M.-A Renard, W. Iraqi, A. Idbaih, S. Paris, et al. Temozolomide for low-grade gliomas: Predictive impact of 1p/19q loss on response and outcome Neurology, May 22, 2007; 68(21): 1831 - 1836. [Abstract] [Full Text] [PDF]

				R. B. Jenkins, H. Blair, K. V. Ballman, C. Giannini, R. M. Arusell, M. Law, H. Flynn, S. Passe, S. Felten, P. D. Brown, et al. A t(1;19)(q10;p10) Mediates the Combined Deletions of 1p and 19q and Predicts a Better Prognosis of Patients with Oligodendroglioma. Cancer Res., October 15, 2006; 66(20): 9852 - 9861. [Abstract] [Full Text] [PDF]

				S. A. Grossman, K. A. Carson, T. T. Batchelor, G. Lesser, T. Mikkelsen, J. B. Alavi, S. Phuphanich, T. Hammour, J. D. Fisher, and J. G. Supko The Effect of Enzyme-Inducing Antiseizure Drugs on the Pharmacokinetics and Tolerability of Procarbazine Hydrochloride Clin. Cancer Res., September 1, 2006; 12(17): 5174 - 5181. [Abstract] [Full Text] [PDF]

				C. Walker, B. Haylock, D. Husband, K. A. Joyce, D. Fildes, M. D. Jenkinson, T. Smith, J. Broome, D. G. du Plessis, and P. C. Warnke Clinical use of genotype to predict chemosensitivity in oligodendroglial tumors Neurology, June 13, 2006; 66(11): 1661 - 1667. [Abstract] [Full Text] [PDF]

				F. F. Lang and M. R. Gilbert Diffusely Infiltrative Low-Grade Gliomas in Adults J. Clin. Oncol., March 10, 2006; 24(8): 1236 - 1245. [Abstract] [Full Text] [PDF]

				K. A. Jaeckle, K. V. Ballman, R. D. Rao, R. B. Jenkins, and J. C. Buckner Current Strategies in Treatment of Oligodendroglioma: Evolution of Molecular Signatures of Response J. Clin. Oncol., March 10, 2006; 24(8): 1246 - 1252. [Abstract] [Full Text] [PDF]

				R. Stupp, M. E. Hegi, M. J. van den Bent, W. P. Mason, M. Weller, R. O. Mirimanoff, J. G. Cairncross, and on behalf of the European Organisation for Researc Changing paradigms--an update on the multidisciplinary management of malignant glioma. Oncologist, February 1, 2006; 11(2): 165 - 180. [Abstract] [Full Text] [PDF]

				F. M. Boyle, S. L. Eller, and S. A. Grossman Penetration of intra-arterially administered vincristine in experimental brain tumor Neuro-oncol, October 1, 2004; 6(4): 300 - 306. [Abstract] [PDF]

				K. Hoang-Xuan, L. Capelle, M. Kujas, S. Taillibert, H. Duffau, J. Lejeune, M. Polivka, E. Criniere, Y. Marie, K. Mokhtari, et al. Temozolomide As Initial Treatment for Adults With Low-Grade Oligodendrogliomas or Oligoastrocytomas and Correlation With Chromosome 1p Deletions J. Clin. Oncol., August 1, 2004; 22(15): 3133 - 3138. [Abstract] [Full Text] [PDF]

				M. Sanson, S. Cartalat-Carel, S. Taillibert, M. Napolitano, L. Djafari, J. Cougnard, H. Gervais, F. Laigle, A. Carpentier, K. Mokhtari, et al. Initial chemotherapy in gliomatosis cerebri Neurology, July 27, 2004; 63(2): 270 - 275. [Abstract] [Full Text] [PDF]

				C. Lebrun, D. Fontaine, A. Ramaioli, F. Vandenbos, S. Chanalet, M. Lonjon, J. F. Michiels, V. Bourg, P. Paquis, M. Chatel, et al. Long-term outcome of oligodendrogliomas Neurology, May 25, 2004; 62(10): 1783 - 1787. [Abstract] [Full Text] [PDF]

				M. Brada, L. Viviers, C. Abson, F. Hines, J. Britton, S. Ashley, S. Sardell, D. Traish, A. Gonsalves, P. Wilkins, et al. Phase II study of primary temozolomide chemotherapy in patients with WHO grade II gliomas Ann. Onc., December 1, 2003; 14(12): 1715 - 1721. [Abstract] [Full Text] [PDF]

				A. Pace, A. Vidiri, E. Galie, M. Carosi, S. Telera, A. M. Cianciulli, P. Canalini, D. Giannarelli, B. Jandolo, and C. M. Carapella Temozolomide chemotherapy for progressive low-grade glioma: clinical benefits and radiological response Ann. Onc., December 1, 2003; 14(12): 1722 - 1726. [Abstract] [Full Text] [PDF]

				E. G. Shaw Presidential Symposium on Low-Grade Glioma Neuro-oncol, July 1, 2003; 5(3): 151 - 152. [PDF]

				W. A. Weiss, M. J. Burns, C. Hackett, K. Aldape, J. R. Hill, H. Kuriyama, N. Kuriyama, N. Milshteyn, T. Roberts, M. F. Wendland, et al. Genetic Determinants of Malignancy in a Mouse Model for Oligodendroglioma Cancer Res., April 1, 2003; 63(7): 1589 - 1595. [Abstract] [Full Text] [PDF]