Safety and efficacy of thalidomide in patients with POEMS syndrome: a multicentre, randomised, double-blind, placebo-controlled trial

Misawa, Sonoko; Sato, Yasunori; Katayama, K.; Nagashima, Kengo; Aoyagi, Reiko; Sekiguchi, Yukari; Sobue, Gen; Koike, Haruki; Yabe, Ichiro; Sasaki, Hidenao; Watanabe, Osamu; Takashima, Hiroshi; Nishizawa, Masatoyo; Kawachi, Izumi; Kusunoki, Susumu; Mitsui, Yosuke; Kikuchi, Seiji; Nakashima, Ichiro; Ikeda, Shu Ichi; Kohara, Nobuo; Kanda, Takashi; Kira, Jun Ichi; Hanaoka, Hideki; Kuwabara, Satoshi

doi:10.1016/s1474-4422(16)30157-0

Cited by 70 publications

(62 citation statements)

References 28 publications

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“…Similar to other angiogenic factors, GDF15 induced the pro-angiogenic effects through the phosphorylation of Src and its downstream pathways of AKT, MAPK, and NF-κB signaling that are reported to be the important pathways in regulation of angiogenesis [15][16][17][18]. Thalidomide has anti-inflammatory, immunomodulatory, and antiangiogenic activities [19][20][21]. In this study, we demonstrated that thalidomide could suppress the in vitro and in vivo chemotherapy-damaged HCC-induced angiogenesis through targeting GDF15-induced activation of Src and its downstream pathways.…”

Section: Discussionmentioning

confidence: 99%

Angiogenesis enhanced by treatment damage to hepatocellular carcinoma through the release of GDF15

Dong

Zheng

et al. 2018

Cancer Medicine

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Transarterial chemoembolization (TACE) is the standard treatment for unresectable hepatocellular carcinoma (HCC). Hypoxia‐induced angiogenesis by TACE is linked to treatment failure; however, whether the chemotherapeutic damage of TACE to HCC could increase tumor angiogenesis has not been explored. The molecular effects of chemotherapy‐damaged HCC cells on the neo‐angiogenesis were investigated in vitro and in vivo. The expression of growth differentiation factor 15 (GDF15) was significantly upregulated in HCC cells exposed to chemotherapeutic agents. GDF15 from chemotherapy‐damaged HCC cells promoted the in vitro proliferation, migration, and tube formation of endothelial cells. The pro‐angiogenic effect of GDF15 was through the activation of Src and its downstream AKT, MAPK, and NF‐κB signaling, which was blocked by thalidomide. The use of thalidomide significantly attenuated the in vivo chemotherapy‐damaged HCC cells‐promoted angiogenesis in nude mice. In conclusion, the chemotherapeutic damage in TACE to HCC could promote tumor angiogenesis via the increased release of GDF15. Thalidomide could reverse these pro‐angiogenic effects.

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Section: Discussionmentioning

confidence: 99%

Angiogenesis enhanced by treatment damage to hepatocellular carcinoma through the release of GDF15

Dong

Zheng

et al. 2018

Cancer Medicine

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“…The primary objective was to reduce VEGF levels by post-treatment week 24; a greater reduction was observed in the thalidomide treatment group. However, this study has been criticized for not having a clinical outcome and for the low number of patients included therein, and it is not possible to consider thalidomide-based treatment as appropriate standard treatment for this condition [16].…”

Section: Discussionmentioning

confidence: 99%

POEMS Syndrome: A Multidisciplinary Diagnostic Challenge

Enciso¹,

Aponte²,

Rodríguez³

et al. 2017

J Clin Case Rep

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POEMS syndrome is a paraneoplastic phenomenon associated with polyneuropathy and paraproteinemia that arises out of the clonal expansion of plasma tumor cells. Its other distinguishing features include sclerotic bone lesions, increased vascular endothelial growth factor levels, Castleman disease alterations in lymph node biopsy and association with organomegaly, endocrinopathy, cutaneous lesions, papilledema, extravascular volume overload and thrombocytosis. Although established diagnostic criteria exist, the fact that the disease is rare and shares similar clinical manifestations with non-neoplastic conditions means that in most cases patients are diagnosed at latestage, when multiple complications have appeared and treatments for other conditions have already been given. Therefore, a high degree of suspicion combined with a multidisciplinary approach are requisites for attaining precise diagnosis and providing timely treatment. Due to the wide differential diagnosis that the syndrome´s clinical features encompass as well as its subsequent favourable responses to bone marrow transplant and diverse chemotherapy treatments, clinicians from diverse fields should include the POEMS syndrome within polyneuropathy differential diagnoses that require specific diagnostic tests. Herein, we present our case study in which we emphasize diagnosis and treatment of patients treated at our institution.

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“…In the first RCT in POEMS syndrome, 25 patients eligible for systemic therapy but not ASCT, were randomised to either thalidomide + dexamethasone or placebo + dexamethasone for 24 weeks, before proceeding to a 48-month open-label safety study where all patients received thalidomide [51]. At 24-weeks, reduction rate of VEGF (the primary endpoint) was significantly greater in the treatment group.…”

Section: Managementmentioning

confidence: 99%

POEMS syndrome: clinical update

Brown

Ginsberg

2018

J Neurol

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POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) is a rare paraneoplastic syndrome, caused by a plasma cell proliferative disorder, which is most commonly lambda restricted. The neurological hallmark, which forms one of the mandatory criteria for diagnosis, is a subacute onset demyelinating neuropathy, which can be rapidly disabling and painful. A number of multi-system features are also characteristic of this disorder, and certainly not restricted to those included in its acronym, which though limited, remains a useful and memorable name, helping distinguish POEMS syndrome from other paraproteinaemic neuropathies. The discovery of vascular endothelial growth factor (VEGF) in association with POEMS syndrome has been extremely useful in aiding clinical diagnosis, and monitoring response to treatment, as well as helping understand the underlying mechanism of disease. Interestingly, however, treatment targeting VEGF has been disappointing, suggesting other disease mechanisms or inflammatory processes are also important. Current understanding of the pathogenesis of POEMS syndrome is outlined in detail in the accompanying article by Cerri et al. Here, we review the clinical features of POEMS syndrome, differential diagnosis and available treatment options, based on current literature.

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Safety and efficacy of thalidomide in patients with POEMS syndrome: a multicentre, randomised, double-blind, placebo-controlled trial

Cited by 70 publications

References 28 publications

Angiogenesis enhanced by treatment damage to hepatocellular carcinoma through the release of GDF15

Angiogenesis enhanced by treatment damage to hepatocellular carcinoma through the release of GDF15

POEMS Syndrome: A Multidisciplinary Diagnostic Challenge

POEMS syndrome: clinical update

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