Phase II Study of Weekly Vinblastine in Recurrent or Refractory Pediatric Low-Grade Glioma Eric Bouffet, Regina Jakacki, Stewart Goldman, Darren Hargrave, Cynthia Hawkins, Manohar Shroff, Juliette Hukin, Ute Bartels, Nicholas Foreman, Stewart Kellie, Joanne Hilden, Michael Etzl, Beverly Wilson, Derek Stephens, Uri Tabori, and Sylvain Baruchel Eric Bouffet, Cynthia Hawkins, Manohar Shroff, Ute Bartels, Derek Stephens, Uri Tabori, and Sylvain Baruchel, Hospi- tal for Sick Children, University of Toronto, Toronto, Ontario; Juliette Hukin, British Columbia Children’s Hospital, Vancouver, British Columbia; Beverly Wilson, University of Alberta Hospital, Edmonton, Alberta, Canada; Regina Jakacki, Children’s Hospital of Pittsburgh, Pittsburgh, PA; Stewart Goldman, Children’s Memorial Medical Center, Chicago, IL; Nicholas Foreman, The Children’s Hospital, Denver, CO; Joanne Hilden, Peyton Manning Chil- dren’s Hospital at St Vincent, Indianapo- lis, IN; Joanne Hilden, The Children’s Hospital at The Cleveland Clinic, Cleve- land, OH; Michael Etzl, Phoenix Chil- dren’s Hospital, Phoenix, AZ; Darren Hargrave, The Royal Marsden Hospital, Sutton, United Kingdom; and Stewart Kellie, The Children’s Hospital at West- mead, Westmead, New South Wales, Australia. Submitted January 6, 2011; accepted January 11, 2012; published online ahead of print at www.jco.org on March 5, 2012. Supported by the Ontario Institute for Cancer Research (formerly the Ontario Institute Research Network) through funding provided by the Government of Ontario (Grant No. 02-11-0261). Authors’ disclosures of potential con- flicts of interest and author contribu- tions are found at the end of this article. Clinical Trials repository link available on JCO.org. Corresponding author: Eric Bouffet, MD, FRCP(C), Hospital for Sick Chil- dren, 555 University Ave, Toronto, Ontario, Canada M5G 1X8; e-mail: eric.bouffet@sickkids.ca. © 2012 by American Society of Clinical Oncology 0732-183X/12/3099-1/$20.00 DOI: 10.1200/JCO.2011.34.5843 A B S T R A C T Purpose To evaluate the efficacy of single-agent vinblastine in pediatric patients with recurrent or refractory low-grade glioma. Patients and Methods Patients were eligible if they had experienced previous treatment failure (chemotherapy and/or radiation) for incompletely resected or unresectable low-grade glioma (LGG). Vinblastine (6 mg/m 2 ) was administered weekly for 1 year unless unacceptable toxicity or progression (confirmed on two consecutive imaging studies) occurred. Results Fifty-one patients (age range, 1.4 to 18.2 years; median age, 7.2 years) were prospectively enrolled onto this phase II study. Fifty patients had previously received at least one prior regimen of chemotherapy, and 10 patients had previously received radiation treatment. Fifty patients were evaluable for response; 18 patients (36%) had a complete, partial, or minor response, and 31 patients completed 1 year of treatment. At a median follow-up of 67 months, 23 patients had not experienced progression; three patients have died. Five-year overall survival was 93.2%  3.8%, and 5-year progression-free survival was 42.3%  7.2%. Toxicity was manageable and mostly hematologic, although a few patients needed transfusions. Conclusion Weekly vinblastine seems to be a reasonable alternative to radiation for pediatric patients with LGG who have experienced treatment failure with first-line chemotherapy. The 5-year progression- free survival observed in this phase II trial is comparable to results observed with first-line chemotherapy in chemotherapy-naive patients. The role of single-agent vinblastine and other vinca alkaloid in the management of pediatric LGGs deserves further investigation. J Clin Oncol 30. © 2012 by American Society of Clinical Oncology INTRODUCTION The management of pediatric low-grade gliomas (LGGs) that cannot be completely resected has evolved considerably during the last two decades. Although radiation used to be the standard treat- ment for incompletely resected or unresectable LGGs, chemotherapy and observation have now progressively become the most commonly used op- tions after initial diagnosis, depending on several factors including tumor location, amount of resid- ual tumor, age, and/or association with neurofibro- matosis type 1 (NF1). 1 Although no strict guidelines have been implemented regarding first-line therapy, many clinicians currently consider chemotherapy as the first-line treatment option, particularly for the younger population. 1 The results of several proto- cols have been reported, with response rates varying from 13% to 70%. 2-8 However, event-free survival (EFS), defined as the need to consider another inter- vention to control tumor progression, has been consistently less than 50% at 5 years with these regimens. 3,5-9 This calls into question the exact ben- efit of these interventions, and more importantly, this raises the need to better define long-term strate- gic options for these patients rather than limiting reports to short-term results of initial management. Few studies have evaluated the efficacy of interven- tions after failure of initial management. In 2000, a pilot study of weekly vinblastine in patients with recurrent LGG yielded promising results. 10,11 The choice of vinblastine was based on evidence of activ- ity of vinca alkaloids in pediatric LGG in early chem- otherapy studies. 2,12 The objective of this phase II study was to confirm the activity of vinblastine and to evaluate its long-term benefit in patients who had JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T © 2012 by American Society of Clinical Oncology 1 http://jco.ascopubs.org/cgi/doi/10.1200/JCO.2011.34.5843 The latest version is at Published Ahead of Print on March 5, 2012 as 10.1200/JCO.2011.34.5843 Copyright 2012 by American Society of Clinical Oncology Downloaded from jco.ascopubs.org on March 17, 2013. For personal use only. No other uses without permission. Copyright © 2012 American Society of Clinical Oncology. All rights reserved.