PCV Chemotherapy Plus Radiation Improves Survival in Low-Grade Glioma

Jan C. Buckner, MD

In a phase III study, a combination of radiation therapy and procarbazine, CCNU, and vincristine (PCV) prolonged both overall survival (OS) and progression-free survival (PFS) compared with radiation therapy (RT) alone for patients with grade 2 glioma, said Jan C. Buckner, MD, chair of oncology, Mayo Clinic, Rochester, Minnesota.¹ The benefit appeared strongest for patients with oligodendroglioma (O) and oligo-astrocytoma (OA).

Buckner reported the results during the initial Plenary Session at the 2014 Society for Neuro-Oncology’s (SNO) Annual Meeting in Miami. The study results build on Buckner and colleagues’ previous work presented earlier this year at the 2014 ASCO Annual Meeting. The report at ASCO focused on the long-term results of PCV given with RT,² and found that grade 2 glioma patients with less than gross total tumor resection or who were aged ≥40 years experienced a prolonged OS and PFS compared with RT alone. In that report, males and patients with A or A-dominant OA had worse outcomes.

A 2012 report from the same group found an improvement in OS but not PFS in the patient group receiving RT and PCV versus RT alone.³

The data reported at SNO focused on the treatment impact of RT alone versus RT and PCV combination therapy according to histologic type. The 251 patients included in the study were either aged <40 years with a subtotal resection or biopsy or aged >40 years with some type of resection and supratentorial grade 2 O, OA, or astrocytoma (A). Patients were accrued for the study between 1998 and 2002; 107 had O, 79 had OA, and 65 had A.

Patients were divided by age, histology, Karnofsky Performance Status, and the presence or absence of contrast enhancement on the preoperative imaging study. Patients were then randomized to RT alone (54 Gy in 30 fractions) or RT followed by 6 cycles of PCV chemotherapy. A log rank test was used to compare survival and PFS distributions for each histologic type.

Median OS for the PCV versus control arms was 13.3 versus 7.8 years (P = .002) overall, and not reached versus 10.8 years (P = .008), 11.4 years versus 5.9 years (P = .05), and 7.7 versus 4.4 years (P = .31), in the O, OA, and A cohorts, respectively. Median PFS was 10.4 versus 4 years overall (P <.001), and not reached versus 6 years (P <.001), 8.9 versus 3 years (P = .01), and 3.7 versus 1.8 years (P = .06), respectively.

This is the first prospective study to show treatment-related survival as it relates to PCV and RT, Buckner said.

There were no treatment-related deaths. The most common side effects in the study were fatigue, anorexia, nausea, and vomiting. Nausea was more common with the RT and PCV combination. “The toxicity level was acceptable and similar to many chemotherapy options,” Buckner said.

Researchers next plan to assess RT versus the RT and PCV combination according to the molecular markers 1p/19q codeletion, IDH mutations, and genomic analyses. The hypothesis is that patients with 1p/19q deletion and IDH mutations will likely benefit from PCV, Bucker said.

Buckner et al’s study involved a collaboration of researchers from around the United States and Canada, including Wake Forest University, The University of Texas MD Anderson Cancer Center, Wayne State University School of Medicine, and Barrow Neurological Institute.

References

1. Buckner J, Shaw E, Pugh S, et al. R9802: Phase III study of radiation therapy (RT) with or without procarbazine, CCNU, and vincristine (PCV) in low-grade qlioma: results by histologic type. Presented at: 19th Annual Meeting of the Society for Neuro-Oncology; November 13-16, 2014; Miami, FL. Abstract AT-13.
2. Buckner J et al. J Clin Oncol. 32:5s, 2014 (suppl; abstr 2000).
3. Shaw EG, Wang M, Coons SW, et al. Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: initial results of RTOG 9802. J Clin Oncol. 2012;30:3065-70.

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