A pilot study of edrecolomab (Panorex, 17-1A antibody) and capecitabine in patients with advanced or metastatic adenocarcinoma

Edrecolomab (Panorex^®) is a monoclonal antibody directed against the 17-1A antigen located on the cell surfaces of carcinomas. Clinical activity has been seen in colon and breast cancer. This trial investigated the feasibility of combining edrecolomab with the oral fluoropyrimidine capecitabine (Xeloda^®).

Patients received a loading dose of edrecolomab 500 mg intravenously (IV) on day-14, followed 2 weeks later by 100 mg IV every 28 days (day 1). Capecitabine was administered to single-patient cohorts at escalating doses of 1500, 2000, and 2500 mg/m²/day in two equally divided doses for 14 of 21 days, beginning on day 1. Additional patients were enrolled at the 2500 mg/m²/day dose level to better define the toxicities of combination therapy. Toxicity assessment was the primary endpoint.

Twenty seven patients with advanced or metastatic adenocarcinoma were enrolled on this study: 20 were evaluable for toxicity and 18 for response. The most common toxicities were elevated liver enzymes, diarrhea, and hand-foot syndrome. In cycle 1, grade 3 hand-foot syndrome was seen in two patients, and grade 3 diarrhea in one patient. Grade 2 toxicities included diarrhea, hand-foot syndrome, anemia, leukopenia, and transaminitis. Cumulative hand-foot syndrome was observed in four patients treated beyond two cycles. Three patients had edrecolomab infusion reactions during the course of treatment. One complete response and two partial responses were seen. Nine patients had disease stabilization lasting a median of 17.5 weeks (range 14.5-28+).

Edrecolomab and capecitabine may be safely given in combination to patients with advanced or metastatic adenocarcinoma. Clinical activity is seen in this heavily pretreated patient population.     

Efficacy of bevacizumab plus irinotecan in children with recurrent low-grade gliomas—a Pediatric Brain Tumor Consortium study

Background

A phase II study of bevacizumab (BVZ) plus irinotecan (CPT-11) was conducted in children with recurrent low-grade glioma to measure sustained response and/or stable disease lasting ≥6 months and progression-free survival.

Methods

Thirty-five evaluable patients received 2 doses (10 mg/kg each) of single-agent BVZ intravenously 2 weeks apart and then BVZ + CPT-11 every 2 weeks until progressive disease, unacceptable toxicity, or a maximum of 2 years of therapy. Correlative studies included neuroimaging and expression of tumor angiogenic markers (vascular endothelial growth factor [VEGF], VEGF receptor 2, hypoxia-inducible factor 2α, and carbonic anhydrase 9).

Results

Thirty-five evaluable patients (median age 8.4 y [range, 0.6–17.6]) received a median of 12 courses of BVZ + CPT-11 (range, 2–26). Twenty-nine of 35 patients (83%) received treatment for at least 6 months. Eight patients progressed on treatment at a median time of 5.4 months (range, 1–17.8). Six patients (17.7%) still in follow-up have had stable disease without receiving additional treatment for a median of 40.1 months (range, 30.6–49.3) from initiating therapy. The 6-month and 2-year progression-free survivals were 85.4% (SE ± 5.96%) and 47.8% (SE ± 9.27%), respectively. The commonest toxicities related to BVZ included grades 1–2 hypertension in 24, grades 1–2 fatigue in 23, grades 1–2 epistaxis in 18, and grades 1–4 proteinuria in 15. The median volume of enhancement decreased significantly between baseline and day 15 (P < .0001) and over the duration of treatment (P < .037).

Conclusion

The combination of BVZ + CPT-11 appears to produce sustained disease control in some children with recurrent low-grade gliomas.     

A Novel Handheld Device for Use in Remote Patient Monitoring of Heart Failure Patients—Design and Preliminary Validation on Healthy Subjects

Remote patient monitoring (RPM) holds great promise for reducing the burden of congestive heart failure (CHF). Improved sensor technology and effective predictive algorithms can anticipate sudden decompensation events. Enhanced telemonitoring systems would promote patient independence and facilitate communication between patients and their physicians. We report the development of a novel hand-held device, called Blue Box, capable of collecting and wirelessly transmitting key cardiac parameters derived from three integrated biosensors: 2 lead electrocardiogram (ECG), photoplethysmography and bioelectrical impedance (bioimpedance). Blue Box measurements include time intervals between consecutive ECG R-waves (RR interval), time duration of the ECG complex formed by the Q, R and S waves (QRS duration), bioimpedance, heart rate and systolic time intervals. In this study, we recruited 24 healthy subjects to collect several parameters measured by Blue Box and assess their value in correlating with cardiac output measured with Echo-Doppler. Linear correlation between the heart rate measured with Blue Box and cardiac output from Echo-Doppler had a group average correlation coefficient of 0.80. We found that systolic time intervals did not improve the model significantly. However, STIs did inversely correlate with increasing workloads.     

Congenital paediatric atlantoaxial dislocation: clinico-radiological profile and surgical outcome

Introduction

Congenital atlantoaxial dislocation (AAD) is the most common bony abnormality affecting the craniovertebral junction. The paediatric population has specific problems like preoperative diagnostic difficulties, precise neurological examination, radiological diagnosis, surgical problems including physical fitness to tolerate surgery (including problems of anaesthesia), technical difficulties in surgery and problems related to immobilization.

Material and methods

A total of 229 consecutive paediatric (≤18?years) patients of AAD visited our centre from the period of January 1997 to August 2011. Twenty-nine cases were excluded from the study as these cases were diagnosed as CVJ tuberculosis, 31 cases were excluded as they were traumatic and the remaining 169 cases were retrospectively analysed. These patients were operated by a single experienced surgeon (the senior author) at the Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow. The preoperative and the postoperative clinical evaluation of the patient was done by the Kumar and Kalra myelopathic scoring system. The score was recorded in the preoperative period, at the time of discharge, at 3?months follow-up and at 6?months follow-up.

Results

Ninety-four were males and 75 were females. The age range was 4 to 18?years with mean age 9.96?±?3.78?years. The follow-up ranged from 3 to 120?months with mean follow-up being 39.03?±?13.38?months. One hundred five cases were of fixed/irreducible AAD, and 64 were cases of mobile/reducible AAD. Majority of these cases presented with features of pyramidal tract involvement, and 108 cases had compromised pulmonary function test. One hundred thirty-seven cases had improved outcome, and 18 cases were in the same grade in the postoperative period with only 14 cases either deteriorated or died.

Conclusions

Congenital paediatric AAD are a different subset of abnormalities and have a satisfactory outcome. Preoperative evaluation must also include identification of various syndromes associated with paediatric AAD and respiratory reserve. Cormack–Lehane grade can be helpful in selecting borderline cases for postoperative need of tracheostomy. Majority of the cases have a good outcome, and therefore, surgery should be offered even in severe grade.     

Clinical, radiological profile and outcome in pediatric Spetzler–Martin grades I–III arteriovenous malformations

Background  

Treatment of pediatric arteriovenous malformations (AVMs) is always a challenge considering their hemorrhagic presentation, associated morbidity and mortality, and the potential long life span of these children. Spetzler–Martin grades I–III are the grey zones as far as the treatment options are concerned. With a generous multimodality approach, one can reduce the morbidity and mortality to a considerable extent.