2
Journal Name: Drug Safety
Article Title: Cancer chemotherapy and cardiac arrhythmias: a review
Author names: Tamargo J, Caballero R, Delpón E
Author Affiliations: Department of Pharmacology, School of Medicine, University Complutense, Madrid.
Electronic Supplementary Table 3. Case-reports of cardiac arrhythmias induced by chemotherapy drugs
Drug / Cancer / SVT / AF / Sinus bradycardiaAVB / QT
prolongation / PVCs/VT/VF/SCD
Alemtuzumab
Lenihan et al. [1] / 8, mycosis fungoides/Sézary syndrome / 1 / 1 VT
Keating et al. [2] / 76 y, T-cell prolymphocytic leukemia / 1
Amsacrine
Falkson [3] / 50-y M, liver cancer
38-y M, liver cancer / 1 SCD
Multiple PVCs/SCD
Von Hoff et al. [4] / 42-y F, myelogenous leukemia / 1 VF and death
Foldes et al. [5] / 28-y F, acute lymphoblastic leukemia / 1 VF
Anthracyclines
Bethell et al. [6] / 47-y F, 48-y M, 56-y F / 3 SB, 1 AVB
Kishi et al. [7] / 16-y F, acute lymphoblastic leukemia / 1 TdP
Arsenic trioside
Unnikrishnan et al. [8] / 3, APL / 3 / 3 TdP
Naito et al. [9] / 23-y and 51-y, F / 2 TdP
Bortezomib
Molteni et al. [10] / 39-y F, breast cancer / ST
Lee et al. [11] / 65-y F, MM / Complete AVB
Dasanu et al. [12] / 1, MM / Complete AVB
Capecitabine
Ang et al. [13] / 75-y M, rectosigmoid adenocarcinoma / 1 / SB (30-40 bpm), cardiac arrest
Tunio et al. [14] / 1, rectum adenocarcinoma / SB
Carmustine + BMT
Kanj et al. [15] / 3 F, 2 breast carcinoma (37-y and 41-y), 1 melanoma (39-y) / 3 ST /
Cisplatin (ipi)
Schlaeffer et al. [16] / 1, Hodgkin lymphoma / SB
Hashimi et al. [17] / 51-y woman, ovary carcinoma / SVT
Canobio et al. [18] / 60-y F, squamous cell lung carcinoma / PSVT
Menard et al. [19] / 65 M, lung carcinoma / 1
Altundag et al. [20] / 35-y M, MM / SB (35 bpm)
Cisplatin and etopoxide
Petrella et al. [21] /
65-y F
/ AFCyclophosphamide + etoposide
Sculier et al. [22] / 1 / / Transient AVB
Cytarabine
Stamatopoulos et al. [23] / 35-y F, acute myelogenous leukemia / / SB (38 bpm)
Kumagawa et al. [24] / 20-y Japanese F, acute myeloid leukemia / / SB
Cil et al. [25] / 1, non-Hodgkin lymphoma / / SB
Docetacel
Palma et al. [26] / 46-y F, infiltrating ductal breast carcinoma / 1
Doxorubicin (alone or in combination)
Wortman et al. [27] / 3 / 2 SCD, 1 VT/VF shortly after drug administration
Couch et al. [28] / 18-y M, osteogenic sarcoma / VF and SCD
Oster et al. [29] / 74-y M, SCLC / 1
Montella et al. [30] / 53-y M, diffuse B-cell gastric lymphoma / 1
Killicap et al. [31] / 36-y F / / Complete AVB and ventricular asystole
Rudzinski et al. [32] / 48-y F, breast cancer / VT and cardiac arrest
Epirubicin
Okamoto et al. [33] / F, breast cancer / Sino-atrial block
Fludarabine
Chung-Lo et al. [34] / 22-y M, acute myeloid leukemia / / SB (48 bpm)
5-Fluorouracil (alone or in combination)
May et al. [35] / 54-y M, 3 F (57, 60 and 65 y) with colorectal carcinoma /
ST with intermittent AF
/ PVCs5-Fluorouracil + capecitabine
Stewart et al. [36] / 70-y M, colon adenocarcionoma / / SB (35 bpm)
66-y M, esophageal adenocarcinoma / / SB (40 bpm), AVB (grade 1) / Monomorphic VT
64-y, esophageal adenocarcinoma / / First degree AVB
72-y F, colon cancer / / QTc 492 ms / TdP
5-Fluorouracil + cisplatin
Hrovatin et al. [37] / 1, head-neck cancer / / VT and cardiac arrest
Gemcitabine
Ciotti et al. [38] / 70-y M, pancreatic adenocarcinoma / 1 (ventricular response 400 bpm)
Santini et al. [39] / 78-y man, pancreatic adenocarcinoma / 1 PAF
Ferrari et al. [40] / 2 F (72-y, 73-y), NSCLC / 2 PAF
Tavil et al. [41] / 65-y man, NSCLC / 1
High-dose chemotherapy (cyclophosphamide+tiotepa) + stem cell transplantation
Ramireddy et al. [42] / 35-y F breast cancer / / Complete AVB
Ifosfamide
Mulller et al. [43] / 1, Ewing sarcoma with multiple metastases / SVT
Interleukin-2
Oleksowicz et al. [44] / 49-y M, renal cell carcinoma / Sustained VT
Methotrexate
Gasser et al. [45] / 61-y F, metastatic breast cancer / PACs / Multiple PVCs
Ketunnen et al. [46] / 35-y M, erythrodermic psoriasis / PVCs (up to 580 per hour) and VF
Perez-Verdia et al. [47] / 36-y F, osteosarcoma / SB / NSVT
Mitoxantrone
Benekli et al. [48] / 56-y M, lymphoblastic leukemia / SB (38 bpm)
Chan-Tack et al. [49] / 80-y F, acute leukemia / SB (20-30 bpm)
Paclitaxel
Rowinski et al. [50] / 68-y F, ovarian carcinoma / PVCs, NSVT
58-y F, ovarian carcinoma / PVCs
48-y F, NSCLC / PVCs, VT
58-y F, NSCLC / LBBB / NSVT
50-y M, NSCLC / Complete AVB
Moscetti et al. [51] / 62-y F, NSCLC / 1
Lombardi et al. [52] / 58-y F, metastatic breast cancer / 1
Paclitaxel, carboxiplatin and bevacizumab
Zekri et al. [53] / 1, non-small cell lung cancer / SB (39 bpm)
Rituximab
Arai et al. [54] / 79-y Japanese male, mantle cell lymphoma / Transient VT
Cervera et al. [55] / 1, non-Hodgkin´s diffuse large B-cell lymphoma / Complete AVB
Sorafenib
Mego et al. [56] / 57-y M, metastatic renal cell carcinoma / 1
Thalidomide
Hinterseer et al. [57] / 67-y M, urothelial carcinoma / Third degree AVB
Trastuzumab
Ferguson et al. [58] / 38-y F, breast cancer / VT
Olin et al. [59] / 69-y F, breast cancer / 1
Tu et al. [60] / 50-y F / Complete LBBB
Vemurafenib
Iddawela et al [61] / 50-y, M, melanoma / 511msec (grade 3)
Vincristine
Mandel et al. [62] / 72-y M, lymposarcoma / PVCs
Vorinostat
Lynch et al. [63] / 49-y M, cutaneous T-cell lymphoma / TdP (QTc 826 ms)
* Drugs are listed alphabetically.
AF: atrial fibrillation. AVB: atrio-ventricular block. BMT: bone marrow transplantation. Ipi: intrapericardial infusion. LBBB: left bundle brach block. MM: multiple myeloma. NSCLC: non-small-cell lung cancer. NSVT: non-sustained ventricular tachycardia. PACs: premature atrial contraction. PAF: paroxysmal atrial fibrillation. PVCs: premature ventricular contractions. SA: sino-atrial. SB: sinus bradycardia. SCD: sudden cardiac death. SCLC: small-cell lung cancer. SCT: stem cell transplantation. ST: Sinus tachyardia. SVT: supraventricular tachycardia. TdP: torsade de pointes. VF: ventricular fibrillation. VT: ventricular tachycardia.
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