Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study.

BACKGROUND: We evaluated bevacizumab with metronomic etoposide among recurrent malignant glioma patients in a phase 2, open-label trial. METHODS: A total of 59 patients, including 27 with glioblastoma (GBM) and 32 with grade 3 malignant glioma, received 10 mg kg(-1) bevacizumab biweekly and 50 mg m(-2) etoposide daily for 21 consecutive days each month. The primary end point was a 6-month progression-free survival, and secondary end points included safety and overall survival. Vascular endothelial growth factor (VEGF), VEGFR-2, carbonic anhydrase 9 (CA9) and hypoxia-inducible factor-2alpha (HIF-2alpha) were assessed semiquantitatively in archival tumours using immunohistochemistry and were correlated with outcome. RESULTS: Among grade 3 and GBM patients, the 6-month progression-free survivals were 40.6% and 44.4%, the radiographic response rates were 22% and 37% and the median survivals were 63.1 and 44.4 weeks, respectively. Hypertension predicted better outcome among both grade 3 and GBM patients, whereas high CA9 and low VEGF were associated with poorer progression-free survival (PFS) among those with GBM. The most common grade > or = 3 adverse events included neutropaenia (24%), thrombosis (12%), infection (8%) and hypertension (3%). Two patients had asymptomatic, grade 1 intracranial haemorrhage and one on-study death occurred because of pulmonary embolism. CONCLUSION: Bevacizumab with metronomic etoposide has increased toxicity compared with previous reports of bevacizumab monotherapy. Its anti-tumour activity is similar to that of bevacizumab monotherapy or bevacizumab plus irinotecan. (ClinicalTrials.gov: NCT00612430).

Comparison of the anticalculus effect of two soluble pyrophosphate dentifrices with and without a copolymer.

A two phase, six month, double blind clinical study was conducted to compare the effect on supragingival calculus deposits of a dentifrice containing 1.30% soluble pyrophosphate (from 2.0% tetrasodium pyrophosphate) with and without the presence of 1.50% of a copolymer of methoxyethylene and maleic acid. In Phase I of the study, male and female adult subjects were stratified into two balanced groups according to baseline calculus scores. They received an oral prophylaxis and were assigned to the use of either a dentifrice containing 1.30% soluble pyrophosphate and 1.50% copolymer or to a placebo dentifrice that did not contain the anticalculus ingredients. After three months use of the products, the subjects received a calculus examination. The subjects were then entered into Phase II of the study where they were restratified into two balanced groups. They again received an oral prophylaxis and were assigned to the use of either a dentifrice containing 1.30% soluble pyrophosphate with no copolymer or to a placebo dentifrice. The results from the three month calculus examination indicated that the dentifrice containing soluble pyrophosphate and a copolymer reduced supragingival calculus deposits by 29.54%, as compared to the placebo dentifrice (less than 99% level of confidence). The results from the six month calculus examinations indicated that the dentifrice containing soluble pyrophosphate without the copolymer did not provide a statistically significant reduction in supragingival calculus after an oral prophylaxis. Thus, it is concluded that the presence of the copolymer in the soluble pyrophosphate dentifrice was essential for obtaining a statistically significant anticalculus effect.