Abstract | PURPOSE: MATERIALS AND METHODS: An in vitro study using lymphoma cell lines and a pilot study on relapsed/refractory DLBCL patients were conducted to investigate the effects and mechanism of the combination of roflumilast and chemotherapy. The complete response (CR), overall response rate (ORR), and 1-year progression-free survival (PFS) were analyzed. RESULTS: We found that roflumilast is efficient when combined with other chemotherapy drugs, especially cytarabine. Synergistic effects between these two drugs influence the translation of mammalian target of rapamycin and myeloid cell leukemia 1, resulting in apoptosis and inhibition of B-cell lymphoma proliferation. In clinical setting, the roflumilast group showed better rates of CR (46.2% vs. 34.6%), ORR (76.9% vs. 53.8%), and 1-year PFS (50.0% vs. 25.9%) compared with the control group, though not statistically significant. The roflumilast group showed a higher incidence of asthenia and gastrointestinal adverse events. However, grade 3 or 4 adverse events were similar in both groups. CONCLUSION: We found that roflumilast, when combined with ESHAP chemotherapy, for relapsed/refractory DLBCL was clinically active and well tolerated. This combined treatment was able to suppress PI3K activity, which is correlated with the degree of clinical response.
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Authors | Do Young Kim, Jehyun Nam, Joo-Seop Chung, Sang-Woo Kim, Ho-Jin Shin |
Journal | Cancer research and treatment
(Cancer Res Treat)
Vol. 54
Issue 1
Pg. 301-313
(Jan 2022)
ISSN: 2005-9256 [Electronic] Korea (South) |
PMID | 33940789
(Publication Type: Journal Article)
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Chemical References |
- Aminopyridines
- Benzamides
- Cyclopropanes
- Phosphodiesterase 4 Inhibitors
- Cytarabine
- Roflumilast
- Etoposide
- Cisplatin
- Methylprednisolone
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Topics |
- Aged
- Aminopyridines
(administration & dosage)
- Antineoplastic Combined Chemotherapy Protocols
(administration & dosage)
- Benzamides
(administration & dosage)
- Cisplatin
(administration & dosage)
- Cyclopropanes
(administration & dosage)
- Cytarabine
(administration & dosage)
- Etoposide
(administration & dosage)
- Female
- Humans
- Lymphoma, Large B-Cell, Diffuse
(drug therapy, mortality)
- Male
- Methylprednisolone
(administration & dosage)
- Middle Aged
- Phosphatidylinositol 3-Kinases
(drug effects)
- Phosphodiesterase 4 Inhibitors
(administration & dosage)
- Pilot Projects
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