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CEOP/IVE/GDP alternating regimen compared with CEOP as the first-line therapy for newly diagnosed patients with peripheral T cell lymphoma: results from a phase 2, multicenter, randomized, controlled clinical trial
- Source :
- Genome Medicine, Vol 12, Iss 1, Pp 1-13 (2020), Genome Medicine
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- Background Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)/CHOP-like chemotherapy is widely used in peripheral T cell lymphoma (PTCL). Here we conducted a phase 2, multicenter, randomized, controlled trial, comparing the efficacy and safety of CEOP/IVE/GDP alternating regimen with CEOP in newly diagnosed PTCL. Methods PTCL patients, except for anaplastic large cell lymphoma-anaplastic lymphoma kinase positive, were 1:1 randomly assigned to receive CEOP/IVE/GDP (CEOP, cyclophosphamide 750 mg/m2, epirubicin 70 mg/m2, vincristine 1.4 mg/m2 [maximum 2 mg] on day 1, and prednisone 60 mg/m2 [maximum 100 mg] on days 1–5 every 21 days, at the first and fourth cycle; IVE, ifosfamide 2000 mg/m2 on days 1–3, epirubicin 70 mg/m2 on day 1, and etoposide 100 mg/m2 on days 1–3 every 21 days, at the second and fifth cycle; and GDP, gemcitabine 1000 mg/m2 on days 1 and 8, cisplatin 25 mg/m2 on days 1–3, and dexamethasone 40 mg on days 1–4 every 21 days, at the third and sixth cycle) and CEOP (every 21 days for 6 cycles). Analysis of efficacy and safety was of the intent-to-treatment population. The primary endpoint was a complete response rate at the end of treatment. Meanwhile, whole exome sequencing and targeted sequencing were performed in 62 patients with available tumor samples to explore prognostic biomarkers in this cohort as an exploratory post hoc analysis. Results Among 106 patients, 53 each were enrolled to CEOP/IVE/GDP and CEOP. With 51 evaluable patients each in two groups, a complete response rate of the CEOP/IVE/GDP group was similar to that of the CEOP group (37.3% vs. 31.4%, p = 0.532). There was no difference in median progression-free survival (PFS; 15.4 months vs. 9.2 months, p = 0.122) or overall survival (OS; 24.3 months vs. 21.9 months, p = 0.178). Grade 3–4 hematological and non-hematological adverse events were comparable. Histone modification genes were most frequently mutated (25/62, 40.3%), namely KMT2D, KMT2A, SETD2, EP300, and CREBBP. Multivariate analysis indicated that CREBBP and IDH2 mutations were independent factors predicting poor PFS and OS (all p KMT2D predicting poor PFS (p = 0.002). Conclusions CEOP/IVE/GDP alternating regimen showed no remission or survival advantage to standard chemotherapy. Future clinical trials should aim to develop alternative regimen targeting disease biology as demonstrated by recurrent mutations in epigenetic factors. Trial registration The study was registered on ClinicalTrial.gov (NCT02533700) on August 27, 2015.
- Subjects :
- Male
0301 basic medicine
Oncology
medicine.medical_treatment
lcsh:Medicine
CHOP
Deoxycytidine
Dexamethasone
Alternating regimen
0302 clinical medicine
Antineoplastic Combined Chemotherapy Protocols
Genetics (clinical)
Etoposide
education.field_of_study
Ifosfamide
Middle Aged
Prognosis
Vincristine
030220 oncology & carcinogenesis
Peripheral T cell lymphoma
Molecular Medicine
Female
medicine.drug
Epirubicin
medicine.medical_specialty
Prognostic biomarker
lcsh:QH426-470
Population
Overall response rate
Drug Administration Schedule
03 medical and health sciences
Internal medicine
Exome Sequencing
Genetics
medicine
Humans
education
Cyclophosphamide
Molecular Biology
Aged
Chemotherapy
business.industry
Research
lcsh:R
Lymphoma, T-Cell, Peripheral
Gemcitabine
lcsh:Genetics
Regimen
030104 developmental biology
Prednisone
Cisplatin
business
Subjects
Details
- ISSN :
- 1756994X
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Genome Medicine
- Accession number :
- edsair.doi.dedup.....ca5539b85ec842d75dc1c00a4353860e