Synergistic Anticancer Effect of a Combination of Chidamide and Doxorubicin Against Peripheral T-Cell Lymphoma

Background: Patients with relapsed or refractory PTCL have a poor overall prognosis. Chidamide, an oral novel histone deacetylase inhibitor, has been approved to be used in patients diagnosed with relapsed or refractory peripheral T cell lymphoma（PTCL）in China.

Patients and methods: 42 patients with different subtypes of relapsed or refractory PTCL were enrolled. They were treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or combination chidamide. The primary end point was overall response rate (ORR). We investigated the effect of chidamide and/or Doxorubicin in PTCL cell lines HUT78 and H9, and explored the molecular mechanism for the cytotoxicity. In addition, we further validated the combined effect of the two drugs through an immunodeficient mouse model.

Results: Compared with patients in CHOP group, those in the combined group had superior progression-free survival (PFS). Monotherapy in PTCL showed a limited response and considerable toxicity. Here, we examined the effects of the combination of low dose Chidamide and Doxorubicin in PTCL cell lines in vivo and in vitro. The synergistic cytotoxic effect of chidamide plus Doxorubicin was confirmed in PTCL cell lines. The cell cycle distribution results showed that combination caused G2/M cell cycle arrest. Moreover, combined treatment in a murine xenograft model resulted in increased apoptosis in tumor tissues and reduced tumor growth.

Conclusion: Overall, the combination of Chidamide and CHOP may be a promising therapeutic strategy for PTCL and provides an effective approach to suppress this lymphoma. Yet further clinical evaluations are required to substantiate the conclusion.

No relevant conflicts of interest to declare.