Cediranib in combination with various anticancer regimens: results of a phase I multi-cohort study

Background Cediranib is a highly potent vascular endothelial growth factor (VEGF) signaling inhibitor of all three VEGF receptors. This phase I, single-center, dose-finding study was designed primarily to investigate the safety and pharmacokinetics (PK) of cediranib with various anticancer regimens in patients with advanced solid tumors. Experimental design Oral cediranib 20, 30, and/or 45 mg/day was given in combination with standard mFOLFOX6; docetaxel; irinotecan; irinotecan and cetuximab; or pemetrexed. The novel study design allowed simultaneous evaluation of the safety and PK of these regimens with cediranib in one study. Secondary assessments included a preliminary evaluation of efficacy. Results Fifty-nine patients received cediranib and were evaluable for safety. The most common adverse events across the study were fatigue and diarrhea (both n = 52). The most common CTC grade ≥ 3 adverse events were neutropenia (n = 19) and fatigue (n = 16). Cediranib did not appear to have a major effect on the PK profile of any chemotherapy agent tested. A preliminary assessment of efficacy showed that objective responses were achieved in some patients (n = 6) who had previously progressed on similar regimens without cediranib. Conclusion In this group of heavily pretreated patients, the study design permitted simultaneous assessment of multiple treatment arms. Treatment with cediranib and the various anticancer regimens was generally well tolerated, with no apparent PK interaction and preliminary evidence of antitumor activity.     

Endovascular repair of para-anastomotic aortic aneurysms

BACKGROUND: Para-anastomotic aneurysms involving the aorta and iliac arteries can occur years after aortic surgery and are at risk for rupture and erosion into surrounding structures. We report on our continued experience with patients who have been treated for these lesions with endovascular management as an alternative to traditional open repair. METHODS: Patients who underwent endovascular repair of para-anastomotic aneurysms involving the distal aortic arch, descending thoracic aorta, abdominal aorta, or iliac arteries were prospectively followed up in a database. Patient comorbidities, initial aortic pathology, initial graft configuration, aneurysm characteristics, evidence of infection, type and configuration of endograft used, and follow-up were analyzed. RESULTS: From 1997 to 2006, 53 patients with 65 para-anastomotic aneurysms were treated with endovascular stent grafts. Patients who were originally treated for aortoiliac occlusive disease presented significantly later than those treated for aneurysmal disease (15.8 vs 8.9 years, P < .01) The initial technical success rate was 98%. Endoleaks were identified in six patients (11%) < or =1 month of surgery, and three required reintervention, including open conversions. Endoleak complications were significantly associated with patients who had symptomatic para-anastomotic aneurysms (P = .01). Perioperative mortality after endovascular repair was 3.8%. Overall mortality within a mean follow-up of 18 months was 49% and was significantly associated with older age at the time of endovascular treatment (P = .03). CONCLUSION: Endovascular repair of para-anastomotic aneurysms involving the aorta and iliac arteries is technically feasible and is associated with a low perioperative morbidity and mortality. Close follow-up is required to identify endoleaks. Long-term survival is limited in older patients. We recommend endovascular stent graft repair for para-anastomotic aneurysms in anatomically suitable patients.     

Incidence and distribution of lower extremity deep vein thrombosis in rehabilitation patients: implications for screening

Patients admitted to in-patient rehabilitation programs have an increased risk for developing deep venous thrombosis (DVT). However, the utility of screening for lower extremity DVT using duplex ultrasound in this high-risk population is not well characterized. The purpose of this study is to identify whether or not screening lower-extremity duplex exams are indicated in this high-risk population. Screening lower extremity duplex exams were performed on all patients admitted to the rehabilitation center at Mt. Sinai Hospital over a 3-year period. Charts were reviewed for patient age, gender, diagnosis, date of screening and follow-up duplex exams, presence and location of venous thrombosis at each duplex exam, history of anticoagulation, and medical DVT prophylaxis. The presence of DVT at screening, the location of DVT along the lower extremity, and the outcome of calf DVT were analyzed in terms of gender, underlying diagnosis, and history of DVT prophylaxis. Lower extremity DVT was detected in 34% of patients. Twenty-three percent of patients had isolated calf vein thrombosis. Men were more likely than women to have DVT. Calf DVTs progressed in 3% of patients over an average follow-up of 2 weeks. The presence of DVT, its location along the lower extremity, and the outcome of calf vein DVT had no significant relationship to underlying diagnosis or history of prophylaxis. Screening duplex exams to detect lower extremity DVT in rehabilitation patients is useful. Screening altered management in 26% of patients, prompting either anticoagulation or repeat duplex exam.     

Endovascular stent-graft repair of failed endovascular abdominal aortic aneurysm repair

Despite high initial technical success, the long-term durability of endovascular abdominal aortic aneurysm repair (EVAR) continues to be a concern. Following EVAR, patients can experience endoleaks, device migration, device fractures, or aneurysm growth that may require intervention. The purpose of this study was to review all patients treated with secondary endovascular devices at our institution for failed EVAR procedures. Over an 8-year period, 988 patients underwent EVAR, of whom 42 (4.3%) required secondary interventions involving placement of additional endovascular devices. Data regarding patient characteristics, aneurysm size, initial device type, time until failure, failure etiology, secondary interventions, and outcomes were reviewed. The mean time from initial operation until second operation was 34.1 months. Failures included type I endoleaks in 38 patients (90.5%), type III endoleaks in two patients (4.8%), and enlarging aneurysms without definite endoleaks in two patients (4.8%). The overall technical success rate for secondary repair was 92.9% (39/42). Perioperative complications occurred in nine patients (21.4%), including wound complications (n = 6), cerebrovascular accident (CVA) (n = 1), foot drop (n = 1), and death (n = 1). Mean follow-up following secondary repair was 16.4 months (range 1-50). Eighty-six percent of patients treated with aortouni-iliac devices had successful repairs compared to 45% of patients treated with proximal cuffs. Ten patients (23.8%) had persistent or recurrent type I or type III endoleaks following revision. Of these, four had tertiary interventions, including two patients who had additional devices placed. Failures following EVAR occur in a small but significant number of patients. When anatomically possible, endovascular revision offers a safe means of treating these failures. Aortouni-iliac devices appear to offer a more durable repair than the proximal cuff for treatment of proximal type I endoleaks. Midterm results indicate that these patients may require additional procedures but have a low rate of aneurysm-related mortality. Longer-term follow-up is necessary to determine the durability of these endovascular revisions.