Bortezomib in combination with CHOP as first-line treatment for patients with stage III/IV peripheral T-cell lymphomas: A multicentre, single-arm, phase 2 trial

Seok Jin Kim, Dok Hyun Yoon, Hye Jin Kang, Jin Seok Kim, Seong Kyu Park, Hyo Jung Kim, Jeeyun Lee, Baek Yeol Ryoo, Young Hyeh Ko, Jooryung Huh, Woo Ick Yang, Hee Kyung Kim, Soo Kee Min, Seung Sook Lee, In Gu Do, Cheolwon Suh, Won Seog Kim

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Abstract

Background: We performed a phase II study to evaluate the efficacy of bortezomib in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) as first-line treatment for patients with stage III/IV peripheral T-cell lymphomas (PTCLs) based on our phase I study results. Methods: Patients received bortezomib on days 1 and 8 at a dose of 1.6 mg/m2 in addition to CHOP every 3 weeks for a total of six cycles. Results: Forty-six patients were enrolled: PTCL, not otherwise specified (PTCL-NOS, n = 16), extranodal NK/T-cell lymphoma, nasal type (ENKTL, n = 10), angioimmunoblastic T-cell lymphoma (AITL, n = 8), ALK-negative anaplastic large-cell lymphoma (ALCL, n = 6), cutaneous T-cell lymphoma (CTCL, n = 5) and hepatosplenic T-cell lymphoma (n = 1). Thirty patients achieved complete response (CR, 65%) and the overall response rate was 76% (35/46). Although the CR rate of ENKTL was only 30% (3/10), three subtypes of PTCLs (PTCL-NOS, AITL and ALCL) showed 87% of overall response rate (ORR) (26/30) and 73% of CR rate (22/30). However, the 3-year overall survival and progression-free survival were 47% and 35%, respectively due to frequent relapse after remission. Grade 3/4 leucopenia was the most frequent toxicity whereas neurotoxicity was tolerable: grade 1 or 2 of peripheral neuropathy. Conclusions: The combined treatment of bortezomib and CHOP is an effective and feasible regimen for advanced-stage PTCLs other than ENKTL, with acceptable toxicity. However, future studies exploring new drug combinations are warranted to overcome relapse after remission.

Original languageEnglish
Pages (from-to)3223-3231
Number of pages9
JournalEuropean Journal of Cancer
Volume48
Issue number17
DOIs
Publication statusPublished - 2012 Nov 1

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Peripheral T-Cell Lymphoma
T-Cell Lymphoma
Extranodal NK-T-Cell Lymphoma
Therapeutics
Anaplastic Large-Cell Lymphoma
Recurrence
Cutaneous T-Cell Lymphoma
Leukopenia
Vincristine
Peripheral Nervous System Diseases
Drug Combinations
Prednisone
Doxorubicin
Cyclophosphamide
Disease-Free Survival
Bortezomib
Survival

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kim, Seok Jin ; Yoon, Dok Hyun ; Kang, Hye Jin ; Kim, Jin Seok ; Park, Seong Kyu ; Kim, Hyo Jung ; Lee, Jeeyun ; Ryoo, Baek Yeol ; Ko, Young Hyeh ; Huh, Jooryung ; Yang, Woo Ick ; Kim, Hee Kyung ; Min, Soo Kee ; Lee, Seung Sook ; Do, In Gu ; Suh, Cheolwon ; Kim, Won Seog. / Bortezomib in combination with CHOP as first-line treatment for patients with stage III/IV peripheral T-cell lymphomas : A multicentre, single-arm, phase 2 trial. In: European Journal of Cancer. 2012 ; Vol. 48, No. 17. pp. 3223-3231.
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title = "Bortezomib in combination with CHOP as first-line treatment for patients with stage III/IV peripheral T-cell lymphomas: A multicentre, single-arm, phase 2 trial",
abstract = "Background: We performed a phase II study to evaluate the efficacy of bortezomib in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) as first-line treatment for patients with stage III/IV peripheral T-cell lymphomas (PTCLs) based on our phase I study results. Methods: Patients received bortezomib on days 1 and 8 at a dose of 1.6 mg/m2 in addition to CHOP every 3 weeks for a total of six cycles. Results: Forty-six patients were enrolled: PTCL, not otherwise specified (PTCL-NOS, n = 16), extranodal NK/T-cell lymphoma, nasal type (ENKTL, n = 10), angioimmunoblastic T-cell lymphoma (AITL, n = 8), ALK-negative anaplastic large-cell lymphoma (ALCL, n = 6), cutaneous T-cell lymphoma (CTCL, n = 5) and hepatosplenic T-cell lymphoma (n = 1). Thirty patients achieved complete response (CR, 65{\%}) and the overall response rate was 76{\%} (35/46). Although the CR rate of ENKTL was only 30{\%} (3/10), three subtypes of PTCLs (PTCL-NOS, AITL and ALCL) showed 87{\%} of overall response rate (ORR) (26/30) and 73{\%} of CR rate (22/30). However, the 3-year overall survival and progression-free survival were 47{\%} and 35{\%}, respectively due to frequent relapse after remission. Grade 3/4 leucopenia was the most frequent toxicity whereas neurotoxicity was tolerable: grade 1 or 2 of peripheral neuropathy. Conclusions: The combined treatment of bortezomib and CHOP is an effective and feasible regimen for advanced-stage PTCLs other than ENKTL, with acceptable toxicity. However, future studies exploring new drug combinations are warranted to overcome relapse after remission.",
author = "Kim, {Seok Jin} and Yoon, {Dok Hyun} and Kang, {Hye Jin} and Kim, {Jin Seok} and Park, {Seong Kyu} and Kim, {Hyo Jung} and Jeeyun Lee and Ryoo, {Baek Yeol} and Ko, {Young Hyeh} and Jooryung Huh and Yang, {Woo Ick} and Kim, {Hee Kyung} and Min, {Soo Kee} and Lee, {Seung Sook} and Do, {In Gu} and Cheolwon Suh and Kim, {Won Seog}",
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Kim, SJ, Yoon, DH, Kang, HJ, Kim, JS, Park, SK, Kim, HJ, Lee, J, Ryoo, BY, Ko, YH, Huh, J, Yang, WI, Kim, HK, Min, SK, Lee, SS, Do, IG, Suh, C & Kim, WS 2012, 'Bortezomib in combination with CHOP as first-line treatment for patients with stage III/IV peripheral T-cell lymphomas: A multicentre, single-arm, phase 2 trial', European Journal of Cancer, vol. 48, no. 17, pp. 3223-3231. https://doi.org/10.1016/j.ejca.2012.06.003

Bortezomib in combination with CHOP as first-line treatment for patients with stage III/IV peripheral T-cell lymphomas : A multicentre, single-arm, phase 2 trial. / Kim, Seok Jin; Yoon, Dok Hyun; Kang, Hye Jin; Kim, Jin Seok; Park, Seong Kyu; Kim, Hyo Jung; Lee, Jeeyun; Ryoo, Baek Yeol; Ko, Young Hyeh; Huh, Jooryung; Yang, Woo Ick; Kim, Hee Kyung; Min, Soo Kee; Lee, Seung Sook; Do, In Gu; Suh, Cheolwon; Kim, Won Seog.

In: European Journal of Cancer, Vol. 48, No. 17, 01.11.2012, p. 3223-3231.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Bortezomib in combination with CHOP as first-line treatment for patients with stage III/IV peripheral T-cell lymphomas

T2 - A multicentre, single-arm, phase 2 trial

AU - Kim, Seok Jin

AU - Yoon, Dok Hyun

AU - Kang, Hye Jin

AU - Kim, Jin Seok

AU - Park, Seong Kyu

AU - Kim, Hyo Jung

AU - Lee, Jeeyun

AU - Ryoo, Baek Yeol

AU - Ko, Young Hyeh

AU - Huh, Jooryung

AU - Yang, Woo Ick

AU - Kim, Hee Kyung

AU - Min, Soo Kee

AU - Lee, Seung Sook

AU - Do, In Gu

AU - Suh, Cheolwon

AU - Kim, Won Seog

PY - 2012/11/1

Y1 - 2012/11/1

N2 - Background: We performed a phase II study to evaluate the efficacy of bortezomib in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) as first-line treatment for patients with stage III/IV peripheral T-cell lymphomas (PTCLs) based on our phase I study results. Methods: Patients received bortezomib on days 1 and 8 at a dose of 1.6 mg/m2 in addition to CHOP every 3 weeks for a total of six cycles. Results: Forty-six patients were enrolled: PTCL, not otherwise specified (PTCL-NOS, n = 16), extranodal NK/T-cell lymphoma, nasal type (ENKTL, n = 10), angioimmunoblastic T-cell lymphoma (AITL, n = 8), ALK-negative anaplastic large-cell lymphoma (ALCL, n = 6), cutaneous T-cell lymphoma (CTCL, n = 5) and hepatosplenic T-cell lymphoma (n = 1). Thirty patients achieved complete response (CR, 65%) and the overall response rate was 76% (35/46). Although the CR rate of ENKTL was only 30% (3/10), three subtypes of PTCLs (PTCL-NOS, AITL and ALCL) showed 87% of overall response rate (ORR) (26/30) and 73% of CR rate (22/30). However, the 3-year overall survival and progression-free survival were 47% and 35%, respectively due to frequent relapse after remission. Grade 3/4 leucopenia was the most frequent toxicity whereas neurotoxicity was tolerable: grade 1 or 2 of peripheral neuropathy. Conclusions: The combined treatment of bortezomib and CHOP is an effective and feasible regimen for advanced-stage PTCLs other than ENKTL, with acceptable toxicity. However, future studies exploring new drug combinations are warranted to overcome relapse after remission.

AB - Background: We performed a phase II study to evaluate the efficacy of bortezomib in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) as first-line treatment for patients with stage III/IV peripheral T-cell lymphomas (PTCLs) based on our phase I study results. Methods: Patients received bortezomib on days 1 and 8 at a dose of 1.6 mg/m2 in addition to CHOP every 3 weeks for a total of six cycles. Results: Forty-six patients were enrolled: PTCL, not otherwise specified (PTCL-NOS, n = 16), extranodal NK/T-cell lymphoma, nasal type (ENKTL, n = 10), angioimmunoblastic T-cell lymphoma (AITL, n = 8), ALK-negative anaplastic large-cell lymphoma (ALCL, n = 6), cutaneous T-cell lymphoma (CTCL, n = 5) and hepatosplenic T-cell lymphoma (n = 1). Thirty patients achieved complete response (CR, 65%) and the overall response rate was 76% (35/46). Although the CR rate of ENKTL was only 30% (3/10), three subtypes of PTCLs (PTCL-NOS, AITL and ALCL) showed 87% of overall response rate (ORR) (26/30) and 73% of CR rate (22/30). However, the 3-year overall survival and progression-free survival were 47% and 35%, respectively due to frequent relapse after remission. Grade 3/4 leucopenia was the most frequent toxicity whereas neurotoxicity was tolerable: grade 1 or 2 of peripheral neuropathy. Conclusions: The combined treatment of bortezomib and CHOP is an effective and feasible regimen for advanced-stage PTCLs other than ENKTL, with acceptable toxicity. However, future studies exploring new drug combinations are warranted to overcome relapse after remission.

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