Thromboembolism in Patients With Advanced Gastroesophageal Cancer Treated With Anthracycline, Platinum, and Fluoropyrimidine Combination Chemotherapy: A Report From the UK National Cancer Research Institute Upper Gastrointestinal Clinical Studies Group

Abstract

PurposeData concerning the prevalence of and outcomes related to thromboembolic events (TEs) in patients with advanced gastroesophageal cancer who are undergoing chemotherapy are limited.Patients and MethodsThis was a prospective, exploratory analysis of TEs in a randomized, controlled trial of 964 patients recruited between 2000 and 2005 and treated with epirubicin/platinum/fluoropyrimidine combination chemotherapy for advanced/locally advanced gastroesophageal cancer. Regimens were epirubicin (E), cisplatin (C), fluorouracil (F; ECF); E, C, capecitabine (X; ECX); E, F, oxaliplatin (O; EOF); and EOX. Continuously infused F was administered via a central venous access device (CVAD) with 1 mg of warfarin for thromboprophylaxis. The principal outcome was the incidence of TEs (venous and arterial) in the whole treated patient cohort, according to chemotherapy, associated with CVADs and TE-related prognoses.ResultsThe incidences of any, of venous, and of arterial TEs among 964 treated patients were 12.1% (95% CI, 10.7 to 14.3), 10.1% (95% CI, 8.3 to 12.3), and 2.2% (95% CI, 1.4 to 3.4) respectively. There were fewer TEs in the O compared with the cisplatin groups (EOF/EOX v ECF/ECX: 7.6% v 15.1%; P = .0003). C was identified as a risk factor for TE in multivariate analysis (hazard ratio [HR], 0.51; 95% CI, 0.34 to 0.76; P = .001). There was no difference in the incidence of TEs for the F group compared with the capecitabine groups. The incidence of CVAD-related thrombosis was 7.0% (ECF/EOF arms). Overall survival was worse for patients who experienced TEs versus no TEs (median survival, 7.4 v 10.5 months; HR, 0.8; 95% CI, 0.64 to 0.99; P = .043).ConclusionThis analysis has prospectively quantified the incidence/pattern of TEs among patients with advanced gastroesophageal cancer who were treated with four triplet regimens, has demonstrated a differential thrombogenic effect according to platinum use, and has noted a poorer outcome associated with TE during treatment. Chemotherapy-related TE should contribute to the risk/benefit assessment of treatment.

Acute Aortic Thrombosis in Patients Receiving Cisplatin-Based Chemotherapy

“…Thrombotic events tended to occur later in the treatment course, usually after cycle 3 or 4 of chemotherapy. Cisplatin is known to increase the risk of thromboembolic events and is the agent most commonly implicated in patients with cancer and arterial thrombosis 9,10 . Cisplatin-induced vascular events tend to occur early in the course of treatment, with approximately 45% occurring during the first 2 courses of chemotherapy 5 .…”

Phase I study of orally administered S-1 in combination with epirubicin and oxaliplatin in patients with advanced solid tumors and chemotherapy-naïve advanced or metastatic esophagogastric cancer

“…In terms of the platinum component of combination chemotherapy regimens used in the first-line treatment of advanced esophagogastric cancer, both cisplatin and oxaliplatin appear to be equally effective, with oxaliplatin associated with reduced incidence of certain toxicities, including thromboembolic events [8][9][10]. The fluoropyrimidine component may be administered as infusional 5-FU.…”

Effectiveness and safety of oxaliplatin compared to cisplatin for advanced, unresectable gastric cancer: a systematic review and meta-analysis

“…Systemic chemotherapy is the only effective treatment available in these situations, but it has extremely poor results and the median survival time is invariably shorter than 1 year [4][5][6].…”

“…However, the benefit is small and happens at the cost of increased toxicity [4]. Another platinum compound, oxaliplatin, could be a candidate to replace cisplatin, possibly overcoming problems associated with this drug, mainly the high frequency of nausea and vomiting and the high incidence of thromboembolic events [5].…”