Cancer Research and Treatment

Original Article

Hematologic malignancy

Role of Roflumilast Combined with ESHAP Chemotherapy in Relapsed/Refractory Patients with Diffuse Large B-Cell Lymphoma: Do Young Kim, Jehyun Nam, Joo-seop Chung, Sang-Woo Kim, Ho-Jin Shin; Cancer Res Treat. 2022;54(1):301-313. Published online April 27, 2021; DOI: https://doi.org/10.4143/crt.2020.1371

Purpose
There are unmet needs associated with the current treatment strategies for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) due to the poor treatment outcomes of these strategies. Roflumilast, a selective phosphodiesterase-4 inhibitor used for treating chronic obstructive pulmonary disease, is effective against B-cell malignancy via phosphoinositide 3-kinase (PI3K)–activity suppression. We analyzed the effects of roflumilast combined with ESHAP (etoposide, cisplatin, methylprednisolone, and cytarabine) chemotherapy in experimental and clinical settings.
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.

Citations

Citations to this article as recorded by

Roflumilast attenuates doxorubicin and cyclophosphamide combination-induced chemobrain in rats through modulation of NLRP3/ASC/caspase-1/GSDMD axis
Georgette Eskander, Sherihan G. Abdelhamid, Sara A. Wahdan, Sara M. Radwan
Life Sciences.2025; 362: 123378. CrossRef
The multifaceted role of phosphodiesterase 4 in tumor: from tumorigenesis to immunotherapy
Huili-li Ren, Shao-hui Zhang, Pei-yuan Li
Frontiers in Immunology.2025;[Epub] CrossRef
Roflumilast tópico y oral en dermatología. Una revisión narrativa
M. Mansilla-Polo, E. Gimeno, D. Morgado-Carrasco
Actas Dermo-Sifiliográficas.2024; 115(3): 265. CrossRef
cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment
Hongying Zhang, Yongliang Liu, Jieya Liu, Jinzhu Chen, Jiao Wang, Hui Hua, Yangfu Jiang
Journal of Hematology & Oncology.2024;[Epub] CrossRef
[Translated aticle] Topical and Oral Roflumilast in Dermatology: A Narrative Review
M. Mansilla-Polo, E. Gimeno, D. Morgado-Carrasco
Actas Dermo-Sifiliográficas.2024; 115(3): T265. CrossRef
Advances in diagnosis, treatment and prognostic factors of gastrointestinal DLBCL
Qinqiao Lai, Yan Zhao, Haiqing Yan, Hongling Peng
Leukemia Research.2023; 135: 107406. CrossRef

7,505 View
218 Download
5 Web of Science
6 Crossref

Case Report

Primary Histiocytic Sarcoma of the Central Nervous System: Hoonsub So, Sun A Kim, Dok Hyun Yoon, Shin Kwang Khang, Jihye Hwang, Chong Hyun Suh, Cheolwon Suh; Cancer Res Treat. 2015;47(2):322-328. Published online August 29, 2014; DOI: https://doi.org/10.4143/crt.2013.163

Abstract PDF PubReader ePub

Histiocytic sarcoma is a type of lymphoma that rarely involves the central nervous system (CNS). Its rarity can easily lead to a misdiagnosis. We describe a patient with primary CNS histocytic sarcoma involving the cerebral hemisphere and spinal cord, who had been initially misdiagnosed as demyelinating disease. Two biopsies were necessary before a correct diagnosis was made. A histologic examination showed bizarre shaped histiocytes with larger nuclei and nuclear atypia. The cells were positive for CD68, CD163, and S-100 protein. As a resection was not feasible due to multifocality, he was treated with highdose methotrexate, but showed no response. As a result, he was switched to high dose cytarabine; but again, showed no response. The patient died 2 months from the start of chemotherapy and 8 months from the onset of symptoms. Since few patients with this condition have been described and histopathology is difficult to diagnose, suspicion of the disease is essential.

Citations

Citations to this article as recorded by

Monocytic meningitis complicating histiocytosis and response to MEK-inhibitor: a case series
Tom Abrassart, Ahmed Idbaih, Damien Roos-Weil, Damien Galanaud, Fleur Cohen-Aubart, Jean-François Emile, Pierre Boncoeur, Zahir Amoura, Danielle Seilhean, Julien Haroche, Matthias Papo
Annals of Hematology.2025; 104(4): 2551. CrossRef
Diagnostic challenges of primary central nervous system histiocytic sarcoma: case report and literature review
Na Liang, Changxian Chen, Dan Yuan, Qiang Xu, Yali Zhan, Yi Zhao, Di Wu, Cheng Yang, Chunming Li
Frontiers in Oncology.2025;[Epub] CrossRef
Transdifferentiation of Hairy Cell Leukemia to Lytic and Mass-Producing Histiocytic Sarcoma: A Novel Head and Neck Example and Review of the Literature
Austin J. Davies, Parnaz Daneshpajouhnejad, Mugdha Patwardhan, Zaizhen Xu, Darren P. Cox
Head and Neck Pathology.2025;[Epub] CrossRef
18FDG PET/MRI in Histiocytic Sarcoma of the Spinal Canal
Kohei Hirota, Feibi Zeng, Junko Inoue Inukai, Munenobu Nogami, Takamichi Murakami
Clinical Nuclear Medicine.2025;[Epub] CrossRef
A rare case of primary central nervous system histiocytic sarcoma harboring a novel ARHGAP45::BRAF fusion: a case report and literature review
Luyi Zhang, Gang Zhang, Han Zheng, Bin Jiang, Yongzhi Ju, Qianqian Duan, Lu An, Hangyu Shi
Brain Tumor Pathology.2024; 41(1): 18. CrossRef
Primary Histiocytic Sarcoma of the Breast: A Case Report and Review of the Literature
Hind Althomali, Haneen Al-Maghrabi, Nora Trabulsi, Jaudah Al-Maghrabi
Cureus.2024;[Epub] CrossRef
Primary CNS histiocytic sarcoma: Two case reports highlighting a novel MIGA2::BRAF gene fusion and genome-wide DNA methylation profiling results
Ryan Cecchi, Doré Guptil, Nicholas Haslett, Alexandra Hristov, Jacob R Bledsoe, Harrison Tsai, John DeWitt, Sean P Ferris
Journal of Neuropathology & Experimental Neurology.2024; 83(10): 882. CrossRef
Case report: Treatment of a rare primary cerebellum histiocytic sarcoma with surgery and radiotherapy
Li Yanchu, Zhang Li, Zhang Qiongwen, Duan Jiayu, Wang Feng
Frontiers in Oncology.2024;[Epub] CrossRef
Leptomeningeal and Dural Dissemination after Irradiation of Primary Central Nervous System Histiocytic Sarcoma : A Case Report and Literature Review
Wataru Matsushita, Yasutomo Momii, Nobuhiro Hata, Kouhei Onishi, Yukari Kawasaki, Kunpei Takao, Mitsuhiro Anan, Minoru Fujiki
Japanese Journal of Neurosurgery.2024; 33(5): 356. CrossRef
Primary intracranial histiocytic sarcomas: a report of six cases and a pooled analysis of individual patient data
Pengcheng Zuo, Mingxin Zhang, Wenhao Wu, Yu Wang, Tian Li, Tao Sun, YuJin Wang, Zhen Wu, Junting Zhang, Liwei Zhang
Journal of Cancer Research and Clinical Oncology.2023; 149(13): 12071. CrossRef
A rare neuromyelitis optica mimic: Primary CNS histiocytic sarcoma
David S Rogawski, Jeffrey J Nirschl, Jamie McDonald, Esther Nie, Nicholas U Schwartz, Hannes Vogel, Brian J Scott, Carl A Gold, Lucas B Kipp
Multiple Sclerosis Journal.2022; 28(10): 1651. CrossRef
New onset headache caused by histiocytic sarcoma of the spinal cord and leptomeninges: a case report
Matthew Silsby, Winny Varikatt, Steve Vucic, Parvathi Menon
BMJ Neurology Open.2021; 3(1): e000147. CrossRef
Clinical Reasoning: A 42-Year-Old Woman With Mysterious Monocytic Meningitis
Meghan E. Nothem, Ryan M. Lee, Jonathan M. Katz, Paul A. Bergl, Ahmed Z. Obeidat
Neurology.2021; 97(9): 449. CrossRef
Primary histiocytic sarcoma in the brain with renal metastasis causing internal ophthalmoparesis and external ophthalmoplegia in a Maine Coon cat
Susana Monteiro, Katherine Hughes, Marie-Aude Genain, Lisa Alves
Journal of Feline Medicine and Surgery Open Reports.2021;[Epub] CrossRef
Clinicopathological characteristics of histiocytic sarcoma affecting the central nervous system in dogs
Izumi Toyoda, William Vernau, Beverly K. Sturges, Karen M. Vernau, John Rossmeisl, Kurt Zimmerman, Chelsea M. Crowe, Kevin Woolard, Michelle Giuffrida, Robert J. Higgins, Peter J. Dickinson
Journal of Veterinary Internal Medicine.2020; 34(2): 828. CrossRef
Nonepithelial Tumors of the Larynx: Single-Institution 13-Year Review with Radiologic-Pathologic Correlation
Andrew C. Ong, Eric H. Huh, Anna J. Moreland, Lisa M. Rooper, Nafi Aygun, Lee M. Akst, Simon R. Best, Majid A. Khan
RadioGraphics.2020; 40(7): 2011. CrossRef
Primary histiocytic sarcoma of the central nervous system: a case report with platelet derived growth factor receptor mutation and PD-L1/PD-L2 expression and literature review
Jackson M. May, Mark R. Waddle, Daniel H. Miller, William C. Stross, Tasneem A. Kaleem, Byron C. May, Robert C. Miller, Liuyan Jiang, Gerald W. Strong, Daniel M. Trifiletti, Kaisorn L. Chaichana, Ronald Reimer, Han W. Tun, Jennifer L. Peterson
Radiation Oncology.2018;[Epub] CrossRef
Primary central nervous system histiocytic sarcoma
Shuang Ma, Michael Schild, Diana Tran, Xuefeng Zhang, Wan-Lin Zhang, Shuai Shen, Hong-Tao Xu, Lian-He Yang, Endi Wang
Medicine.2018; 97(26): e11271. CrossRef
Case of primary central nervous system histiocytic sarcoma with prominent proliferation of histiocytic cells between the trabeculae of reactive glial cells
Emiko Takahashi, Ayako Sakakibara, Toyonori Tsuzuki, Shigeo Nakamura
Neuropathology.2018; 38(6): 609. CrossRef
Primary histiocytic sarcoma presenting as diffuse leptomeningeal disease: Case description and review of the literature
Magda Zanelli, Moira Ragazzi, Giovanni Marchetti, Alessandra Bisagni, Massimo Principi, Daniela Fanni, Elisabetta Froio, Silvia Serra, Eleonora Zanetti, Loredana De Marco, Felice Giangaspero, Stefano Ascani
Neuropathology.2017; 37(6): 517. CrossRef
Pediatric intracerebral histiocytic sarcoma with rhabdoid features: Case report and literature review
Young Hye Kim, Gie‐Taek Yie, Na Rae Kim, In‐Sang Jeon, Hyun Yee Cho, Jae Yeon Seok, Eung Yeop Kim, Kyu Chan Lee
Neuropathology.2017; 37(6): 560. CrossRef
Looking for a Rarity: Histiocytic Sarcoma
Joana de Castro Rocha, Isabel Paiva, Ana Rita Cruz
Journal of Cancer Therapy.2016; 07(02): 79. CrossRef
A Case of Histiocytic Sarcoma Arising in Head and Neck Region with Rhabdoid Differentiation
Jeong Marn Kim, Yun Seok Oh, Dong Wook Lee
Korean Journal of Otorhinolaryngology-Head and Neck Surgery.2016; 59(9): 672. CrossRef
A 43‐Year‐Old Female with Multifocal Cerebral Lesions
Marieke B.B. Nieuwenhuis, Sandra M.A. van der Salm, Joost J.C. Verhoeff, Anneke J. van der Kooi, Ivana Slavujecvic‐Letic, Steven T. Pals, Josephine M.I. Vos
Brain Pathology.2015; 25(3): 371. CrossRef

17,196 View
208 Download
23 Web of Science
24 Crossref

Original Articles

Intrapleural Chemotherapy with Cisplatin and Cytarabine in the Management of Malignant Pleural Effusion: Kee Won Kim, Suk Young Park, Myung Sook Kim, Seok Chan Kim, Eun Hee Lee, So Young Shin, Jong Ho Lee, Jong Bum Kweon, Kuhn Park; Cancer Res Treat. 2004;36(1):68-71. Published online February 29, 2004; DOI: https://doi.org/10.4143/crt.2004.36.1.68

Abstract PDF PubReader ePub

Purpose

The purpose of this study was to evaluate the efficacy of intrapleural chemotherapy (IPC) with cisplatin and cytarabine in the management of malignant pleural effusion (MPE) from non-small-cell lung cancer (NSCLC).

Materials and Methods

A prospective analysis was carried out on 40 patients with pathologically proven MPE from NSCLC who had received IPC. A single dose of cisplatin 100 mg/m² plus cytarabine 1200 mg/m² in 250 ml normal saline was instilled into the pleural space via a chest tube and drained 4 hours later. Patients were evaluated for toxicities and responses at 1, 2, & 3 weeks and then at monthly intervals if possible. Systemic chemotherapy was administered, if the patient agreed to receive it, after achieving complete control (CC) of MPE.

Results

The median duration of chest tube insertion for drainage was 7 (3~32) days. Among the assessable 37 patients, CC and partial control (PC) were 32 (86.5%) and 4 (10.8%) patients, respectively (overall response rate 97.3%). The median duration of response was 12 months (2~23) and there were only two relapses of IPC after achieving CC. Among the 35 patients who were assessable until they died, 28 patients (80.0%) maintained CC until the last follow-up. There was only one toxic death and the toxicities of IPC, versus the results obtained, were deemed acceptable.

Conclusion

The procedures were tolerable to the patients and chemotherapy-induced complications were at an acceptable level. The outcome of this trial indicates that IPC has a superior and long lasting treatment response in the management of patients with MPE from NSCLC.

Citations

Citations to this article as recorded by

Efficacy of hyperthermic intrathoracic chemotherapy for initially diagnosed lung cancer with symptomatic malignant pleural effusion
Zihui Li, Jie Deng, Fei Yan, Li Liu, Yanling Ma, Jianhai Sun
Scientific Reports.2023;[Epub] CrossRef
Survival Benefits for Pulmonary Adenocarcinoma With Malignant Pleural Effusion After Thoracoscopic Surgical Treatment: A Real-World Study
Xin Li, Mingbiao Li, Jinshuang Lv, Jinghao Liu, Ming Dong, Chunqiu Xia, Honglin Zhao, Song Xu, Sen Wei, Zuoqing Song, Gang Chen, Hongyu Liu, Jun Chen
Frontiers in Oncology.2022;[Epub] CrossRef
Modified indwelling pleural catheter versus silver nitrate pleurodesis for the management of malignant pleural effusion
Mohammed F. Abdelghany, Khaled Essmat, Atef Farouk El-Karn, Sahar Farghly Youssif
The Egyptian Journal of Chest Diseases and Tuberculosis.2022; 71(2): 248. CrossRef
Chinese herbal injections versus intrapleural cisplatin for lung cancer patients with malignant pleural effusion: A Bayesian network meta-analysis of randomized controlled trials
Yi-Fang Xu, Yun-Ru Chen, Fan-Long Bu, Yu-Bei Huang, Yu-Xin Sun, Cheng-Yin Li, Jodi Sellick, Jian-Ping Liu, Dan-Mei Qin, Zhao-Lan Liu
Frontiers in Oncology.2022;[Epub] CrossRef
Making cold malignant pleural effusions hot: driving novel immunotherapies
Pranav Murthy, Chigozirim N. Ekeke, Kira L. Russell, Samuel C. Butler, Yue Wang, James D. Luketich, Adam C. Soloff, Rajeev Dhupar, Michael T. Lotze
OncoImmunology.2019; 8(4): e1554969. CrossRef
Efficacy and safety of intrapleural cisplatin versus silver nitrate in treatment of malignant pleural effusion
Mohammad K. El Badrawy, Raed El-Metwally Ali, Asem A. Hewidy, Mohamed A. El-Layeh, Fatma M. F. Akl, Abdelhadi Shebl
Egyptian Journal of Bronchology.2018; 12(1): 98. CrossRef
Biodegradable drug-eluting pellets provide steady and sustainable cisplatin release in the intrapleural cavity: In vivo and in vitro studies
Yin-Kai Chao, Yu-Wen Wen, Kuo-Sheng Liu, Yi-Chuan Wang, Chih-Wei Wang, Shih-Jung Liu
International Journal of Pharmaceutics.2015; 484(1-2): 38. CrossRef

9,271 View
58 Download
7 Crossref

Prognostic Implications of Cytarabine Dose in Consolidation Chemotherapy for the Patients with Acute Myelogenous Leukemia: Jung Hee Lee, Je Hwan Lee, Kyoo Hyung Lee, Hyeseung Bahng, Jin Hee Ahn, Jung Shin Lee, Sang Hee Kim, Woo Kun Kim; J Korean Cancer Assoc. 2000;32(5):954-961.

Abstract PDF: PURPOSE
Increasing the dose of cytarabine in consolidation chemotherapy has been suggested to improve treatment outcome of the patients with acute myelogenous leukemia (AML) in complete remission (CR). We studied an effect of cytarabine dose in consolidation chemotherapy on the survival times.
MATERIALS AND METHODS
From 1989 to 1998, AML patients in CR who received two or more courses of consolidation chemotherapy were included. At the first course of consolidation chemo therapy, all patients received standard dose of cytarabine (100 or 200 mg/m2/day by a continuous infusion for 5 days) plus anthracyclines. At the second or third course, one of three dose levels of cytarabine was given with anthracyclines. Three dose levels of cytarabine were standard dose (SD), intermediate dose (ID, 1 or 2 g/m2/day by a 3-hour infusion for 5 days), and high dose (HD, 3 g/m2 in a 3-hour infusion every 12 hours for total six doses). We retrospectively reviewed clinical records of study patients.
RESULTS
64 patients were included. The median follow-up duration of alive patients was 1,143 days. Estimated 3-year overall survival times were 24% in SD group, 41% in ID group and 56% in HD group (P=0.737). Estimated 3-year disease free survival times were 18%, 16% and 44% in each group (P=0.592). There was no significant difference in toxicity of consolidation chemotherapy between three groups.
CONCLUSION
Although the survival times showed a trend to be longer in the patients who received higher dose of cytarabine as consolidation chemotherapy, there were no statistically significant differences.

3,130 View
22 Download

Treatment of Relapsed ro Refractory Acute leukemia with High / Intermediate - dose Cytarabine and Idarubicin: Seong Chul Kim, Yoo Hong Min, Hyun Jin Noh, Seung Tae Lee, Bo Yong Chung, Jee Sook Hahn, Yun Woong Ko; J Korean Cancer Assoc. 1996;28(2):301-308.

Abstract PDF: Background
The therapeutic outcome for relapsed or refractory adults with acute leukemia is so poor, and it is difficult to expect the long-term disease-free survival in these patients. We evaluated the therapeutic outcome of a salvage chemotherapy consisting of high- or intermediate-dose(HD or ID) cytarabine and a new daunorubicin analogue, idarubicin. Material and method: Twenty one patients with refractory or relapsed acute lymphocytic leukemia(ALL) and 13 patients with acute myeloid leukemia(AML) were treated with a regimen that included idarubicin 12 mg/§³ intravenously daily for 3 days plus HD cytara- bine(3,000 mg/§³ by infusion over 2 hours daily for 3 days) or ID cytarabine(1,000 mg/§³ every 12 hours for six doses). Results: 1) Complete remission(CR) was achieved in thirteen of 34 patients (38%; 10 of relapsed and 3 of refractory): 16 patients(47%) did not respond to the treatment and 5 patients(15%) died during chemotherapy. 2) The median days to the neutrophils over 500/ul was 23 from the initiation of chemotherapy (range 12-39). The significant non-hematologic taxicities were not observed. 3) Two of 13 patients who achieved CR relapsed within 2 months, four relapsed 2 months after CR. Remaining seven patients have been in continuous CR(CCR). 4) For all complete responders, the median CR duration was 6 months, and the projected actuarial disease-free survival rate was 32% at 9 months. For the all patients, the projected overall survival was 15% at 18 months. Conclusion: We found that HD or ID cytarabine and idarubicin can be one of the effective salvage regimens for patients with relapsed acute leukemia. To improve remission rate of refractory cases, the modification of administration and combination therapy with other non-cross resistant drug will be designed.

2,396 View
19 Download

First
Prev
Page of 1
Next
Last

Search