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Cardiac tamponade induced by dabrafenib and trametinib combination therapy for melanoma: Case report.

ABSTRACT: RATIONALE:BRAF and MEK inhibitors (BRAF/MEKi) are targeted therapy for proto-oncogene BRAF mutated metastatic unresectable melanoma. Compared to monotherapy, an increased cardiovascular toxicity is reported with the combination of Dabrafenib and Trametinib. This case report documents Grade 4 cardiac treatment emergent adverse effect of pericardial effusion and cardiac tamponade induced by this combination therapy. PATIENT CONCERNS:A 52 year old man presented with clinical stage II unresectable melanoma with BRAF mutation, was initiated on treatement with Dabrafenib and Trametinib. He complained of generalised edema and increased his weight by 27 kg. This progressed to shortness of breath and he underwent echocardiogram which revealed cardiac tamponade. DIAGNOSES:Emergent pericardiocentesis was performed. No definited pathology was demonstrated in laboratory analysis of pericardial fluid. Re- initiating treatment resulted in cardiac tamponade and pericardiotomy was performed by video-assisted thoracic surgical (VATS). Pericardial biopsy revealed nonspecific chronic inflammation. INTERVENTIONS:Discontinuation of treatment with Dabrafenib and Trametinib and diuretics resolved peripheral edema. Cardiac function normalized after pericardiocentesis and pericardiotomy. OUTCOMES:Treatment with Dabrafenib and Trametinib caused significant peripheral edema and pericardial effusion resulting in cardiac tamponade. Naranjo score suggests probable association of treatment induced pericardial effusion and cardiac tamponade. LESSONS:This is the first documented report of pericardial effusion and cardiac tamponade induced by Dabrafenib and Trametinib. Cardiac toxicity of BRAF/MEK inhibitors is rare but clinicans must monitor for treatment emergent adverse effects.

SUBMITTER: Sundaram VR

PROVIDER: S-EPMC6221704 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Cardiac tamponade induced by dabrafenib and trametinib combination therapy for melanoma: Case report.

Sundaram Vinita Ruth VR Abbas Tahir T

Medicine 20181101 44

<h4>Rationale</h4>BRAF and MEK inhibitors (BRAF/MEKi) are targeted therapy for proto-oncogene BRAF mutated metastatic unresectable melanoma. Compared to monotherapy, an increased cardiovascular toxicity is reported with the combination of Dabrafenib and Trametinib. This case report documents Grade 4 cardiac treatment emergent adverse effect of pericardial effusion and cardiac tamponade induced by this combination therapy.<h4>Patient concerns</h4>A 52 year old man presented with clinical stage II ...[more]

PMID: 30383630

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Project description:Melanoma is a frequent neoplasm in young adult males in reproductive age, 10% of them degenerating into regional and/or distant metastases (MM). The use of BRAF inhibitors (BRAFi) vemurafenib and dabrafenib is effective in MM patients harboring BRAF V600E/K/D mutations. Despite the increased life expectancy in MM patients treated with BRAFi, concerns are raised by the possible side effects and increased risk of gonado- and/or genotoxicity associated with these drugs. However, these aspects are currently under-investigated. Here we report the different fertility outcome in two cases of MM patients, harboring BRAF V600E mutation, that received vemurafenib and dabrafenib respectively. The first patient, 36 years at recruitment in 2015 and seeking fatherhood, had an history of relapsing melanoma since 2002 and undergone to numerous interventions and chemotherapy cycles. In November 2011, following detection of BRAF V600E mutation, a daily treatment with vemurafenib (1,440 mg) was prescribed with preventive gamete cryopreservation. BRAFi was effective in the clinical stabilization of the disease. In 2015, semen evaluation at follow-up showed sperm parameters within the normal range and no signs of alteration of either sperm function or sperm-DNA. On these bases, no contraindications for fatherhood were given. After a month of free intercourses, the 38-year-old partner achieved spontaneous pregnancy with a regular course, normal male fetal karyotype and a full term birth. The second patient, 39 years at recruitment in 2018 and seeking fatherhood, had an history of melanoma since 2012. In 2018, following the evidence of disease relapse and detection of the BRAF V600E mutation, treatment with dabrafenib/trametinib (300 mg/day/2 mg/day) was initiated together with preventive gamete cryopreservation. In 2019, semen evaluation at follow up showed sperm count and motility below the reference values, associated with increased indexes of sperm aneuploidies and sperm DNA fragmentation. Accordingly, access to assisted reproduction technique with cryopreserved spermatozoa was suggested. Differently from dabrafenib that was associated to damage to spermatogenesis, high-dose vemurafenib showed no association with gonadotoxicity and genotoxicity in humans, even at high doses. Although further confirmation are required, our data represent a valued cue in oncofertility counseling to MM patients in addition to preventive cryopreservation.

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Cardiac tamponade induced by dabrafenib and trametinib combination therapy for melanoma: Case report.

Publications

Cardiac tamponade induced by dabrafenib and trametinib combination therapy for melanoma: Case report.

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