Raynaud's phenomenon after combination chemotherapy of testicular cancer, measured by laser Doppler flowmetry. A pilot study

Heier, Mona Skard; Nilsen, Trude; Graver, Vibeke; Aass, Nina; Fosså, Sophie D.

doi:10.1038/bjc.1991.129

Cited by 19 publications

(10 citation statements)

References 14 publications

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“…Some studies showed an exaggerated response to cold not only in patients with RP but also in patients without finger symptoms before testicular chemotherapy [74,98]. An increased central sympathetic vasoconstrictor reflex and an impaired non-neurogenic vasomuscular, auto-regulation was highlighted in patients suffering from RP syndrome after chemotherapy when compared with the control group (patients without RP after chemotherapy) [99].…”

Section: Drugs Enhancing Vasoconstrictionmentioning

confidence: 99%

“…A study in 1995 that included 90 patients treated with cisplatin-based chemotherapy for more than 1 year after testicular cancer found that 37% of them had developed RP after four cycles of chemotherapy combining cisplatin, bleomycin and vinblastine [73]. RP typically appeared 3 to 6 months after the start of chemotherapy and often persisted for several years [74]. The risk factors identified for the development of RP were high cumulative doses of bleomycin and a combination of bleomycin with vinblastine rather than etoposide.…”

Section: Endothelium Damage And/or Neurotoxicitymentioning

confidence: 99%

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Drug‐induced Raynaud's phenomenon: beyond β‐adrenoceptor blockers

Khouri

Blaise

Carpentier

et al. 2016

Brit J Clinical Pharma

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AIMDrug-induced Raynaud's phenomenon (RP) has long been associated with the use of different drugs, including cancer chemotherapy or β-adrenoceptor blockers. However, sources report extremely variable prevalence and the level of evidence for each class is heterogeneous. Moreover, new signals are emerging from case reports and small series. Our objective was therefore to review available evidence about this adverse drug effect and to propose a mechanistic approach of drug-induced RP. METHODSA systematic review of English and French language articles was performed through Medline (1946Medline ( -2015 and Embase (1974Embase ( -2015. Further relevant papers were identified from the reference lists of retrieved articles. RESULTSWe identified 12 classes of drugs responsible for RP, with a variety of underlying mechanisms such as increased sympathetic activation, endothelial dysfunction, neurotoxicity or decreased red blood cell deformability. Cisplatin and bleomycin were associated with the highest risk, followed by β-adrenoceptor blockers. Recent data suggest a possible involvement of tyrosine kinase inhibitors (TKI), through an unknown mechanism. CONCLUSIONDrug-induced RP is a probably underestimated adverse drug event, with limited available evidence regarding its prevalence. Although rare, serious complications like critical digital ischaemia have been reported. When these treatments are started in patients with a history of RP, careful monitoring must be made and, if possible, alternative therapies that do not alter peripheral blood flow should be considered. IntroductionRaynaud's phenomenon (RP) is characterized by transient ischaemia of the extremities in response to environmental stress or emotions [1]. It typically manifests as changes to the fingers, with pallor (vasospasm and decreased blood flow), cyanosis (deoxygenation of the static venous blood) and rubor (reperfusion), often accompanied by pain. RP can be primary (i.e. idiopathic) or secondary to an underlying cause. In both cases, abnormalities of the cutaneous microcirculation are primarily involved in the pathophysiology of RP [2]. The prevalence of RP in the general population varies between 0.5 and 19%, with major geographic variability [3][4][5][6]. While primary RP is the most frequent form (80-90%) [7], RP may also be secondary to various auto-immune diseases (such as systemic sclerosis (SSc), systemic lupus erythematosus, vasculitis, etc.), or other systemic diseases [1]. Several drugs with peripheral vascular effects leading to decreased microvascular perfusion may induce or aggravate RP. Drug-induced RP probably goes unrecognized because of the limited knowledge of this side effect. British Journal of Clinical PharmacologyLiterature reviews and textbooks usually have comprehensively reviewed drugs that have long been known to be responsible for RP [8]. However, new signals are emerging from numerous case reports. Yet, to our knowledge, no systematic review has been performed and little is known about the prevalence and the level of evidence ...

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Section: Drugs Enhancing Vasoconstrictionmentioning

confidence: 99%

Section: Endothelium Damage And/or Neurotoxicitymentioning

confidence: 99%

Drug‐induced Raynaud's phenomenon: beyond β‐adrenoceptor blockers

Khouri

Blaise

Carpentier

et al. 2016

Brit J Clinical Pharma

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“…The clinical features of Raynaud's phenomenon include bilateral or unilateral digital ischemia on cold exposure. Whereas Vogel zang et al [3] found trophic changes of the fingertips in some patients, no trophic skin changes were observed by other in vestigators [11,15]. Digital ischemia led to life-style alterations in 12 of 20 patients of the above-mentioned report [3], Gangrene of the fingers or deterioration with time were not reported.…”

Section: Raynaud' S Phenomenonmentioning

confidence: 87%

“…Since bleomycin is known to cause structural alterations in the small blood ves sels, a minor contribution of anatomical changes cannot be excluded. In a study using laser Doppler flowmetry [15] an exaggerated and prolonged vasoconstrictor response to cold, with a mean flux reduction of 61%, was found. Moreover, the mean restitution time exceeded 7 min.…”

Section: Raynaud' S Phenomenonmentioning

confidence: 99%

Acute and Late Vascular Complications Following Chemotherapy for Germ Cell Tumors

Gerl¹,

Clemm²,

Wilmanns³

1993

Oncol Res Treat

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Side effects of cisplatin-based chemotherapy for germ cell tumors include myelosup-pression, nephro-, neuro- and ototoxicity. These side effects as well as the pulmonary toxicity of bleomycin are dose-dependent. On the contrary, chemotherapy-associated vascular complications are unpredictable. Whereas Raynaud’s phenomenon is observed in a considerable proportion of patients, myocardial infarction, stroke, and pulmonary embolism appear to occur infrequently. The fact that some patients have been in complete remission at the time of myocardial infarction or cerebrovascular accident argues against a tumor-induced complication and is an argument in favor of a possible causative role of chemotherapy. An alteration of the clotting system and vascular smooth muscle tone as well as an endothelial cell damage are discussed to be pathogenetic mechanisms. Pulmonary embolism, on the contrary, seems to be more frequently associated with inferior vena caval obstruction by tumor masses. Presently there is a debate whether, apart from rare acute vascular events, chemotherapy for testicular cancer leads to a long-term alteration of lipid profile and thereby eventually increases cardiovascular risk.

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“…However, it has been shown that disturbed innervations of blood vessels in ª 2006 European Society for Medical Oncology the legs and disturbed perceptions of temperature are longterm complications after RPLND in TCSs [17].…”

Section: Secondary Malignancymentioning

confidence: 99%