Management of venous thromboembolism in colorectal cancer patients treated with bevacizumab

Abstract

Venous thromboembolism associated with use of a central venous access system is an urgent problem in patients treated with bevacizumab (bev). We investigated the effectiveness of Doppler ultrasound imaging (DUS) in the early detection of catheter-related thrombosis for avoidance of severe venous thromboembolism. Patients with metastatic colorectal cancer received either FOLFOX-4 + bev or FOLFIRI + bev. DUS was performed on the deep venous system for detection of thrombus formation during the initial cycle of treatment, followed by re-evaluation after the third cycle in patients with asymptomatic thrombus formation. All patients were followed up until treatment was interrupted. Median duration of follow-up was 484 days (range 72-574). Among 41 enrolled patients, curable symptomatic thrombosis occurred in one, and asymptomatic thrombosis in 21 (51.2%). Of 21 patients undergoing re-evaluation, thrombi remained without progression in 17 patients, and enlargement in 4 patients. In two of the patients in whom there was progression, pulmonary embolism occurred after the sixth cycle. In the asymptomatic group, no thrombi developed as far as the superior vena cava in any patient. In the cases of progression, thrombotic enlargement was observed in all the 4 patients, with decreased vascular flow in 2. Using DUS, we were able to detect asymptomatic thrombosis in the early cycles of treatment, indicating its potential in the monitoring of venous thrombi. In the event of an enlarging asymptomatic thrombosis developing into the superior vena cava along with decreased vascular flow, careful follow-up and appropriate anticoagulant therapy may be recommended without increased risk of bleeding.

Anticoagulant therapy for venous thromboembolism detected by Doppler ultrasound in patients with metastatic colorectal cancer receiving bevacizumab

“…We previously reported the efficacy of Doppler ultrasound (DU) imaging for management of VTE in patients receiving chemotherapy combined with Bev. 14 Our findings suggested that DU is useful for management of VTE associated with a subclavicular implantable CVAS in patients treated with Bev, while D-dimer or other baseline laboratory data were not useful as prognostic factors. In addition, we found that anticoagulant therapy was beneficial for progressive asymptomatic thrombosis, but the indications for such therapy need to be established to avoid severe thromboembolism including PE.…”

“…In our previous study, we prospectively assessed the effectiveness of DU for early identification of catheter-related thrombosis and changes of asymptomatic venous thrombosis during use of Bev. 14 In addition, the purpose of that study was to detect Doppler diagnostic findings independent of clinical findings. In that study, prophylactic anticoagulant therapy for VTE was not given before the start of chemotherapy so as to evaluate asymptomatic thrombus formation.…”

“…An outline of the study design (including the timing of DU) is shown in Figure 1 ; it was the same as in our previous study. 14 DU was performed to assess the deep venous system in the upper extremities on the CVAS side. To detect incipient thrombosis during chemotherapy, DU was first performed after the first course of Bev.…”

Single low-dose targeted bevacizumab infusion in adult patients with steroid-refractory radiation necrosis of the brain: a phase II open-label prospective clinical trial

“…20 Intra-arterial (IA) bevacizumab promises rapid eradication of VEGF and swift resolution of both microvascular pathology and RN symptoms while minimizing known systemic toxicities, including intracranial hemorrhage, uncontrolled hypertension, gastrointestinal tract perforation, venous sinus thrombosis, wound dehiscence, and pulmonary embolus. 14,[21][22][23][24] We previously treated 2 pediatric patients with refractory brain RN by using a single 2.5 mg/kg targeted bevacizumab infusion immediately after osmotic BBBD. 20 Both patients demonstrated remarkable clinical and imaging improvement in less than 12 months, with complete resolution of inflammation-related symptoms and MRI findings at 3 years and no recurrence after 8 years (unpublished data).…”

Targeted intraarterial anti-VEGF therapy for medically refractory radiation necrosis in the brain

“…7,20 There are significant known side effects of bevacizumab including gastrointestinal tract perforation, deep venous thrombosis, venous sinus thrombosis, pulmonary embolus, intracranial hemorrhage, wound dehiscence, and severe hypertension. 1,6,11,12,[21][22][23] These complications are common in the antiangiogenic class of drugs and reflect systemic exposure to bevacizumab. Current intravenous bevacizumab regimens use a dose of 7.5 mg/kg every 3 weeks for 4 cycles.…”