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Purpose: The standard treatment for peripheral T-cell lymphomas (PTCLs) is undetermined. We designed a CHOPE/G regimen (cyclophosphamide, pirarubicin, vincristine, prednisolone, and etoposide alternating with a gemcitabine-based regimen) as the first-line treatment of PTCLs and compared with CHOP (cyclophosphamide, pirarubicin, vincristine, and prednisolone) and CHOPE (CHOP plus etoposide) regimen to evaluate the optimal chemotherapy regimen.Methods: 116 previously untreated PTCL patients received CHOP (N = 46), CHOPE (N = 46), or CHOPE/G (N = 24) regimen at Peking University Cancer Hospital from 2009 to 2017 and were retrospectively analyzed.Results: The overall response rates (ORRs) of the CHOP, CHOPE, and CHOPE/G groups were 82.6%, 76.1%, and 75.0% (p = 0.673), with complete response (CR) rates of 32.6%, 56.5%, and 45.7% (p = 0.063), respectively. Within a median follow-up time of 35.5 months, the 3-year overall survival (OS) rates of the CHOP, CHOPE, and CHOPE/G groups were 37.0%, 47.0%, and 56.3% (p = 0.107), and the 3-year progression-free survival (PFS) rates were 19.9%, 29.9%, and 5.3% (p = 0.093), respectively. Compared with the CHOP regimen alone, CHOPE had a significantly higher CR rate (p = 0.021) with more favorable OS (p = 0.046). The CHOPE/G regimen did not improve the ORR, CR rate, or OS compared with either the CHOP or CHOPE, with a significantly poorer PFS compared with the CHOPE regimen (p = 0.029). Anemia and thrombocytopenia occurred most frequently in the CHOPE/G group (anemia 83.3%, p = 0.035; thrombocytopenia 50%, p = 0.015).Conclusions: Compared with CHOP alone, CHOPE regimen improved the efficacy and survival; while the addition of gemcitabine in the front-line therapy resulted in more adverse events without benefit of survival. [ABSTRACT FROM AUTHOR]