Arterial thrombosis after cisplatin-based chemotherapy for metastatic germ cell tumors

To the EditorAlthough germ cell tumors (GCTs) make up only1% of all human malignancies, they are the mostcommon cancers among men aged 15 to 34 [1].Since the introduction of cisplatin-based chemother-apy in the 1970s, long-term survival rates of 80% areachieved even in metastatic settings [2]. This hasplaced greater emphasis on minimizing therapy-related side effects as they significantly impact thequality of life of long-term survivors. Here wepresent two cases of cisplatin-induced arterialthrombosis in patients receiving chemotherapy formetastatic good prognosis GCTs. We then reviewthe incidence and consider possible mechanisms ofthis phenomenon.Case 1A 58-year-old male was diagnosed with a classicseminoma with retroperitoneal metastases (StageIIc). Remarkable past medical history includesmalignant melanoma treated surgically 15 yearsearlier. The patient presented with a three monthhistory of left testicular enlargement with an elevatedbeta fraction of human gonadotrophic hormone(bHCG) of 49 IU/L (normal B2 IU/L). Anabdominal computed tomography (CT) scanshowed enlarged retroperitoneal lymph nodes in-cluding a mass encasing the renal arteries and half ofthe abdominal aorta. The patient underwent aninguinal orchiectomy and was scheduled for fourcourses of etoposide and cisplatin chemotherapy(EP). After the first cycle, the patient experiencedmild symptoms suggestive of intermittent claudica-tion in the distal right lower extremity. After thesecond cycle of treatment these symptoms worsenedand he was diagnosed with acute ischemia secondaryto thrombosis in the right external iliac artery. Nosmoking history or cardiovascular risk factors wereidentified and investigations ruled out heart diseaseas the precipitating cause. A balloon angioplasty ofthe right common iliac artery, right common femoralartery thrombectomy, and patch angioplasty of theright femoral artery were performed. On discharge,the patient was prescribed clopidogrel and low-doseaspirin for thrombosis prophylaxis. Following reso-lution of the ischemic episode, the patient resumedchemotherapy and completed four cycles of treat-ment as initially planned, achieving a completeresponse. On further follow-up his only complaintis mild bilateral residual neuropathy in the feet. Thepatient remains free of disease 12 months after theinitial diagnosis.Case 2A 37-year-old male was diagnosed with good prog-nosis, stage III testicular cancer of mixed seminomaand non-seminoma histology (95% embryonal car-cinoma, 5% seminoma). The past medical historywas unremarkable. The patient initially presentedwith a left testicular mass; scrotal ultrasound re-vealed a large left testicular lesion and a 4.9 cm massin the left inguinal region. The alpha-feto proteinand bHCG were elevated at 17 IU/L (normal B5)and 155 IU/L, respectively. The patient underwentan orchiectomy and started chemotherapy withbleomycin, etoposide, and cisplatin (BEP). Afterthe first cycle he developed a painful, swollen, andcyanotic right foot with significantly decreased bloodflow and was diagnosed with an acute arterialthrombosis. The patient was admitted to hospitaland treated with thromboembolitic therapy withtissue plasmin activator (tPA), followed with lowmolecular weight heparin. After discharge he con-tinued on chemotherapy with prophylactic heparin,and the second cycle of BEP was well tolerated.However, during the third cycle the patient devel-oped a recurrence of arterial embolic disease in theright leg. Despite many interventions including