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, Shanshan Fan, Yu Chang, Xiyang Liu, Wencai Li, Qianwen Ma, Yang Li, Yan Wang, Lei Zhang, Mingzhi Zhang, Qian Zhao, Shanshan Fan, Yu Chang, Xiyang Liu, Wencai Li, Qianwen Ma, Yang Li, Yan Wang, Lei Zhang, Mingzhi Zhang

Abstract

Objective: 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: Epstein-Barr virus-DNA; extranodal NK/T-cell lymphoma; gemcitabine; pegaspargase; prognosis.

Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
PFS of 64 patients and OS of 55 patients after DDGP regime chemotherapy. (A) The 1-, 2- and 3-year PFS was 77.00%, 67.80% and 62.00%, respectively. (B) The 1-, 2- and 3-year OS was 81.50% 74.9% and 74.90%, respectively. Abbreviations: DDGP, cisplatin, dexamethasone, gemcitabine and pegaspargase; OS, overall survival; PFS, progression-free survival.
Figure 2
Figure 2
Survival curves. (A) PFS is shown for all patients. No significant difference was noted in PFS between the EBV-DNA-positive group and EBV-DNA-negative group. (P=0.812). (B) OS is shown for 55 patients, the EBV-DNA-negative group has a better OS than EBV-DNA-positive group (P=0.046). Abbreviations: DDGP, cisplatin, dexamethasone, gemcitabine and pegaspargase; EPV, Epstein-Barr virus; OS, overall survival; PFS, progression-free survival.
Figure 3
Figure 3
Comparison of PFS and OS curves between patients negative and positive for EBV in the EBV (+) group. (A) Progression-free survival (PFS) is shown for 28 patients negative for EBV (+) group, showing the turned to negative group has a better PFS than remained positive group (P=0.003). (B) OS is shown for 25 patients negative for EBV (+) group, showing the turned to negative group has a better OS than remained positive group (P=0.017). Abbreviations: DDGP, cisplatin, dexamethasone, gemcitabine and pegaspargase; EPV, Epstein-Barr virus; OS, overall survival; PFS, progression-free survival.

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