Procarbazine, CCNU and vincristine (PCV) versus temozolomide chemotherapy for patients with low-grade glioma: a systematic review

// Karim Hafazalla 1, 2 , Arjun Sahgal 3 , Blessing Jaja 2 , James R. Perry 4 and Sunit Das 2, 5 1 Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA 2 Li Ka Shing Knowledge Institute, St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada 3 Department of Radiation Oncology, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada 4 Division of Neurology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada 5 Division of Neurosurgery, University of Toronto, Toronto, ON, Canada Correspondence to: Sunit Das, email: sunit.das@utoronto.ca Keywords: glioma; IDH; low-grade glioma; PCV; temozolomide Received: June 15, 2018      Accepted: July 16, 2018      Published: September 14, 2018 ABSTRACT Low-grade gliomas (LGG) encompass a heterogeneous group of tumors that are clinically, histologically and molecularly diverse. Treatment decisions for patients with LGG are directed toward improving upon the natural history while limiting treatment-associated toxiceffects. Recent evidence has documented a utility for adjuvant chemotherapy with procarbazine, CCNU (lomustine), and vincristine (PCV) or temozolomide (TMZ). We sought to determine the comparative utility of PCV and TMZ for patients with LGG, particularly in context of molecular subtype. A literature search of PubMed was conducted to identify studies reporting patient response to PCV, TMZ, or a combination of chemotherapy and radiation therapy (RT). Eligibility criteria included patients 16 years of age and older, notation of LGG subtype, and report of progression-free survival (PFS), overall survival (OS), and treatment course. Level I, II, and III data were included. Adjuvant therapy with PCV resulted in prolonged PFS and OS in patients with newly diagnosed high-risk LGG. This benefit was accrued most significantly by patients with tumors harboring 1p/19q codeletion and IDH1 mutation. Adjuvant therapy with temozolomide was associated with lower toxicity than therapy with PCV. In patients with LGG with an unfavorable natural history, such as with intact 1p/19q and wild-type IDH1, RT/TMZ plus adjuvant TMZ may be the best option. Patients with biologically favorable high-risk LGG are likely to derive the most benefit from RT and adjuvant PCV.