J Korean Med Sci.  2018 Jun;33(24):e167. 10.3346/jkms.2018.33.e167.

Procarbazine and CCNU Chemotherapy for Recurrent Glioblastoma with MGMT Promoter Methylation

Affiliations
  • 1Department of Neurosurgery, Ajou University School of Medicine, Suwon, Korea.
  • 2Neuro-Oncology Clinic, National Cancer Center, Goyang, Korea.
  • 3Department of Neurosurgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
  • 4Department of Neurosurgery, Seoul National University Bundang Hospital, Seongnam, Korea.
  • 5Department of Neurosurgery, The Catholic University of Korea, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea.
  • 6Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
  • 7Department of Pathology, Seoul National University Hospital, Seoul, Korea.
  • 8Department of Hospital Pathology, The Catholic University of Korea, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 9Department of Neurosurgery, The Catholic University of Korea, St. Vincent's Hospital, Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Suwon, Korea. 72ysh@catholic.ac.kr

Abstract

BACKGROUND
While procarbazine, CCNU (lomustine), and vincristine (PCV) has been an alternative chemotherapy option for malignant gliomas, it is worth investigating whether the combination of only procarbazine and CCNU is comparable because vincristine adds toxicity with uncertain benefit. The purpose of this study was to evaluate the feasibility of procarbazine and CCNU chemotherapy for recurrent glioblastoma multiforme (GBM) with O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation.
METHODS
Eight patients with recurrent GBM following concurrent chemoradiotherapy and temozolomide (TMZ) adjuvant therapy were enrolled in this trial; they received no other chemotherapeutic agents or target therapy. They received CCNU (75 mg/m²) on day 1 and procarbazine (60 mg/m²) through days 11 and 24 every 4 weeks. The median cycle of CCNU and procarbazine was 3.5 (range: 2-6).
RESULTS
One patient achieved stable disease. The median progression-free survival (PFS) with procarbazine and CCNU chemotherapy was eight weeks (range: 5-73), and the PFS rates were 25% and 12.5% at 16 and 30 weeks, respectively. The median overall survival (OS) from the initial diagnosis to death was 40 months, and the median OS from the administration of procarbazine and CCNU chemotherapy to death was 9.7 months (95% confidence interval: 6.7-12.7). Serious adverse events were found at six visits, and two cases were considered to be grade 3 toxicities.
CONCLUSION
The efficacy of procarbazine and CCNU chemotherapy is not satisfactory. This study suggests the need to develop other treatment strategies for recurrent and TMZ-refractory GBM. Trial registry at ClinicalTrials.gov, NCT017337346.

Keyword

Glioblastoma; Nitrosourea; Recurrent; Procarbazine; CCNU

MeSH Terms

Chemoradiotherapy
Diagnosis
Disease-Free Survival
Drug Therapy*
Glioblastoma*
Glioma
Humans
Lomustine*
Methylation*
Procarbazine*
Vincristine
Lomustine
Procarbazine
Vincristine
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