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The DDGP (cisplatin, dexamethasone, gemcitabine, and pegaspargase) regimen for treatment of extranodal natural killer (NK)/T-cell lymphoma, nasal type.

ABSTRACT: Extranodal natural killer/T cell lymphoma (ENKL) is a high invasive disease with poor prognosis. Since there is no consensus on standard chemotherapy, we developed an original chemotherapeutic DDGP (cisplatin, dexamethasone, gemcitabine, and pegaspargase) regimen. We retrospectively analyzed 80 patients who received DDGP chemotherapy. The primary end point was progression-free survival (PFS) and secondary end points were overall survival (OS), complete response rate (CRR), and overall response rate (ORR). The one-year PFS and OS rates were 86.0% and 88.6%, and the 2-year PFS and OS rates were 81.40% and 87.1%, respectively. The ORR and CRR of DDGP chemotherapy were 91.3% and 60.0%. The major adverse events were myelosuppression, digestive tract toxicities, and coagulation disorder. No treatment-related deaths were observed. Our results suggest that the DDGP regimen is a high effective and safe treatment for ENKL.

SUBMITTER: Zhang L

PROVIDER: S-EPMC5295438 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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The DDGP (cisplatin, dexamethasone, gemcitabine, and pegaspargase) regimen for treatment of extranodal natural killer (NK)/T-cell lymphoma, nasal type.

Zhang Lei L Li Sucai S Jia Sisi S Nan Feifei F Li Zhaoming Z Cao Jingyu J Fan Shanshan S Zhang Chao C Su Liping L Wang Jinghua J Xue Hongwei H Zhang Mingzhi M

Oncotarget 20160901 36

Extranodal natural killer/T cell lymphoma (ENKL) is a high invasive disease with poor prognosis. Since there is no consensus on standard chemotherapy, we developed an original chemotherapeutic DDGP (cisplatin, dexamethasone, gemcitabine, and pegaspargase) regimen. We retrospectively analyzed 80 patients who received DDGP chemotherapy. The primary end point was progression-free survival (PFS) and secondary end points were overall survival (OS), complete response rate (CRR), and overall response r ...[more]

PMID: 27517317

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Project description: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).

Project description:Extranodal natural killer/T cell lymphoma-nasal type (EN-NK/T-NT) is extremely rare in Western countries; however, it is the most common subtype of peripheral T cell lymphoma in China. Despite this, there are a limited number of clinicopathological research studies on Epstein-Barr virus (EBV)-negative EN-NK/T-NTs. EBV-negative EN-NK/T-NT is a rare disease type, which has not been fully investigated. If other diagnostic criteria are met, such as the lesions being located predominantly in the upper aerodigestive tract, the presence of angiocentricity or angioinvasion, necrosis and expression of NK/T-cell phenotype, EN-NK/T-NT may be diagnosed, even if EBV is negative. In the present study, 99 cases of EN-NK/T-NTs were analyzed retrospectively, among which seven cases were EBV-negative EN-NK/T-NTs and selected for further investigation. In addition, the present study reviewed previously published research into EN-NK/T-NT, highlighting that EBV-negative EN-NK/T-NT is rare and that its geographical distribution is mainly in countries in Asia, Central America and South America. Patients with EBV-negative EN-NK/T-NT were all of Chinese ethnicity, with a median age of 32 years and primarily female. Furthermore, these patients shared similar clinicopathological characteristics (such as the tumor occurring mainly in the upper aerodigestive tract, the presence of vascular destruction, necrosis and cytotoxic phenotypes) to patients with EBV-positive EN-NK/T-NT. Immunohistochemistry and molecular analysis results indicated that tumor cells were primarily of NK or cytotoxic T origin; however, EBV-encoded small RNAs were not detected in any of these cases. Among the immunochemistry markers, T-bet was statistical significantly different between EBV-positive and -negative cases. Fluorescence in situ hybridization was also performed in two EBV-negative cases, including one case with a co-deletion of 6q21 and PR/SET domain 1 genes. There was only available follow-up data in 3/5 patients who survived for 37–113 months (median, 40 months). As EN-NK/T-NT can be diagnosed, even when EBV is negative, awareness of this subtype may prevent misdiagnosis or delayed diagnosis.

Project description:Extranodal natural killer (NK)/T-cell lymphoma, nasal type (NNKTL) has very unique epidemiological, etiologic, histologic, and clinical characteristics. It is commonly observed in Eastern Asia, but quite rare in the United States and Europe. The progressive necrotic lesions mainly in the nasal cavity, poor prognosis caused by rapid local progression with distant metastases, and angiocentric and polymorphous lymphoreticular infiltrates are the main clinical and histologic features. Phenotypic and genotypic studies revealed that the lymphoma is originated from either NK- or ?? T-cell, both of which express CD56. In 1990, the authors first reported the presence of Epstein-Barr virus (EBV)-DNA and EBV-oncogenic proteins, and EBV has now been recognized to play an etiological role in NNKTL. in vitro studies revealed that a wide variety of cytokines, chemokines, and micro RNAs, which may be produced by EBV-oncogenic proteins in the lymphoma cells, play important roles for tumor progression in NNKTL, and could be therapeutic targets. In addition, it was revealed that the interaction between NNKTL cells and immune cells such as monocytes and macrophages in NNKTL tissues contribute to lymphoma progression. For diagnosis, monitoring the clinical course and predicting prognosis, the measurements of EBV-DNAs and EBV-micro RNAs in sera are very useful. For treatment with early stage, novel concomitant chemoradiotherapy such as DeVIC regimen with local radiotherapy and MPVIC-P regimen using intra-arterial infusion developed with concomitant radiotherapy and the prognosis became noticeably better. However, the prognosis of patients with advanced stage was still poor. Establishment of novel treatments such as the usage of immune checkpoint inhibitor or peptide vaccine with molecular targeting therapy will be necessary. This review addresses recent advances in the molecular understanding of NNKTL to establish novel treatments, in addition to the epidemiologic, clinical, pathological, and EBV features.

Dataset Information

The DDGP (cisplatin, dexamethasone, gemcitabine, and pegaspargase) regimen for treatment of extranodal natural killer (NK)/T-cell lymphoma, nasal type.

Publications

The DDGP (cisplatin, dexamethasone, gemcitabine, and pegaspargase) regimen for treatment of extranodal natural killer (NK)/T-cell lymphoma, nasal type.

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