A phase I study of axitinib (AG-013736) in combination with bevacizumab plus chemotherapy or chemotherapy alone in patients with metastatic colorectal cancer and other solid tumors.

BACKGROUND: Axitinib and bevacizumab are targeted therapies against the vascular endothelial growth factor pathway. METHODS: Patients with previously treated solid tumors received axitinib (starting dose 5 mg twice daily) combined with FOLFOX plus bevacizumab (1, 2, or 5 mg/kg, cohorts 1-3, respectively), FOLFIRI (cohort 4), or FOLFOX (cohort 5). Safety and pharmacokinetics were assessed. RESULTS: Thirty patients were enrolled (n = 16, 8, and 6 for cohorts 1-3, 4, and 5, respectively). Plasma concentrations and pharmacokinetic (PK) parameters were similar when drugs were administered alone and in various combinations. Most treatment-emergent adverse events (AEs) were mild to moderate and clinically manageable (most common: nausea, fatigue, diarrhea, anorexia, hypertension). Two of the four patients receiving axitinib with FOLFOX plus 5 mg/kg bevacizumab experienced dose-limiting toxicity (DLT) of inability to resume treatment for 14 days following treatment interruption (associated AE: hypertension); the maximum tolerated dose of bevacizumab in this combination was 2 mg/kg. No DLTs occurred with axitinib plus FOLFIRI or FOLFOX. Ten patients had RECIST-confirmed partial tumor responses (objective response rate: 33.3%). CONCLUSION: Axitinib is well tolerated in combination with FOLFOX, FOLFIRI, or FOLFOX plus 2 mg/kg bevacizumab. PK interactions appear to be absent.

Accuracy of an enzymatic assay device for serum ethanol measurement.

OBJECTIVE: To determine the accuracy of an enzymatic assay of serum to measure blood ethanol levels in the emergency department. METHODS: A blinded, prospective study of emergency department patients for whom a blood ethanol was ordered and performed. After skin prep with betadine, two blood samples were drawn into separate sodium fluoride-containing vacutainers. One sample was sent to the hospital laboratory for blood ethanol analysis. The other was centrifuged for 5 minutes and the serum was then assayed using the QED A350 Saliva Alcohol Test. Values were then compared by kappa statistic and Pearson's correlation. Sensitivity and specificity calculations were determined for the QED device to detect a blood ethanol > 100 mg/dL. RESULTS: Sixty-six patients were enrolled. The kappa value for QED compared to lab blood ethanol was 0.93. The Pearson's correlation coefficient was 0.94. The QED, in general, tended to overestimate blood ethanol slightly. The QED was 100% sensitive and 82% specific in detecting a blood ethanol > 100 mg/dL. CONCLUSIONS: Analysis of serum using a QED A350' is a sensitive and accurate index of low to moderate increases in blood ethanol appropriate to emergency department, but not legal, interpretation.

Nonimmobilization of surgically treated tuberculosis of spine in children.

Tuberculosis of the spine is still one of the major health problems in developing countries. The treatment is prolonged and the morbidity considerable. The children are kept off active play for many months. Because of the duration of the disease the treatment is expensive for the class of patients usually afflicted by this disease. The older conservative treatment by chemotherapy, found to be inefficient and inadequate, is now being replaced in most world centres by surgical debridement of the tubercular focus. However, these surgical procedures are usually followed and often preceded by attempts of immobilization by various means such as plaster shells, casts, braces, etc. Postsurgical resumption of activities is usually not allowed for many months. We have observed that a pre and postsurgical immobilization is not required in the strict manner as it is being practices by most clinics today. Our study has shown that gadgets such as plaster casts, etc., have no added advantage and are cumbersome for the patients. They also create a management problem for the family. The fear that neurological complications could develop or that the deformity would increase in severity in the absence of immobilization is not correct. During follow-up examination, patients were evaluated for general and local condition, ESR, local radiograms, neurological status, and the resumption of activities. The increase in the deformity is due to the loss of growth in the particular segment rather than the stress on the spine, which could not be totally prevented anyway by external immobilization.