Clinical efficacy of cisplatin, dexamethasone, gemcitabine and pegaspargase (DDGP) in the initial treatment of advanced stage (stage III–IV) extranodal NK/T-cell lymphoma, and its correlation with Epstein-Barr virus

Qian Zhao,1,2 Shanshan Fan,1,2 Yu Chang,1,2 Xiyang Liu,1,2 Wencai Li,2,3 Qianwen Ma,1,2 Yang Li,1,2 Yan Wang,1,2 Lei Zhang,1,2,* Mingzhi Zhang1,2,*1Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, People’s Republic of China; 2Lymphoma Diagnosis and Treatment Center of Henan Province, Zhengzhou, Henan 450000, People’s Republic of China; 3Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Lymphoma Diagnosis and Treatment Center of Henan Province, Zhengzhou, Henan, People’s Republic of China*These authors contributed equally to this workObjective: To evaluate the clinical efficacy and safety of the DDGP regimen in treating extranodal NK/T-cell lymphoma and investigate the correlation between Epstein-Barr virus (EBV)-DNA variation after treatment and the clinical efficacy of NK/T-cell lymphoma.Methods: Sixty-four patients with extranodal NK/T-cell lymphoma received DDGP regimen-based chemotherapy. Short-term and long-term clinical efficacy and adverse reactions were observed. The relationship between EBV-DNA changes before and after therapy and clinical efficacy was investigated.Results: After the DDGP regimen was used as the initial treatment, the short-term clinical efficacy included 39 complete remission (CR) (60.94%), 12 partial remission (PR) (18.75%), 2 stable disease (SD) (3.13%) and 11 progressive disease (PD) (17.18%). Objective response rate (ORR) was 79.69% and 82.82% for disease control rate (DCR). 3-year progression-free survival (PFS) was 62.00% and 3-year overall survive (OS) was 74.90%. Hemocytopenia was the predominant adverse effect. Between EBV-DNA positive group and its negative counterpart, a significant difference was noted in OS (P=0.046), but no difference in ORR, DCR or PFS was observed. In the EBV-DNA positive group, ORR, DCR, PFS and OS were higher for patients whose EBV-DNA copy number decreased within a normal range than patients remained positive (93.33% versus 61.53%, P=0.041 for ORR; 93.33% versus 61.53%, P=0.041 for DCR, P=0.003 for PFS, P=0.017 for OS). The main adverse reactions included bone marrow suppression, gastrointestinal reaction and coagulation dysfunction, which were mitigated and treated after expectant or dose-decrement treatment.Conclusion: DDGP regimen can significantly improve the clinical prognosis of NK/T-cell lymphoma patients with tolerable adverse reactions. The variation in EBV-DNA is correlated with clinical efficacy and prognosis, which provides a theoretical basis for NK/T-cell lymphoma therapy.Clinical trial: In November 2011, this clinical trial was registered on the website: www.ClinicalTrials.gov (No. NCT01501149).Keywords: gemcitabine, pegaspargase, extranodal NK/T-cell lymphoma, Epstein-Barr virus-DNA, prognosis