542 Background: Met, a drug used to treat type 2 diabetes, is being evaluated as an anti-cancer a... more 542 Background: Met, a drug used to treat type 2 diabetes, is being evaluated as an anti-cancer agent. Long-term use is associated with BCH Vit B12 DEF in up to 30%; a subset may develop symptomatic DEF. It is unknown if Vit B12 DEF is due to diabetes or Met use. We examined Vit B12 DEF in NCIC CTG MA.32, an RCT of adjuvant Met vs Pl in non-diabetic BC patients (pts). Methods: This was a DSMC approved central lab analysis in the first 492 (of 3649) high risk N0/N1-3 BC pts receiving standard therapy randomized onto MA.32 (Met 850 mg bid vs Pl bid for 5 years). VitB12 was analysed in baseline and 6 month (mo) fasting plasma; levels <181 pmol/L were DEF, 181 to 221 pmol/L borderline. Methylmalonic acid (MMA) and homocysteine (HC) (elevated in clinical Vit B12 DEF) were assayed in those with Vit B12 levels <222 pmol/L at either time. Hgb was measured locally. Analysis used Spearman’s rank correlation coefficients and Wilcoxon signed rank test for continuous variables and Chi-square test for 2 by 2 tables. Re...
Background: Pelareorep is a Dearing strain of reovirus serotype 3, with demonstrated in vitro and... more Background: Pelareorep is a Dearing strain of reovirus serotype 3, with demonstrated in vitro and in vivo activity in many cancers and synergistic cytotoxic activity with microtubule targeting agents, including taxanes. This study was designed to determine the efficacy and safety of pelareorep + P compared to P alone in mBC. Materials and Methods: This randomized, open-label, phase II study enrolled subjects who had mBC previously exposed to chemotherapy (CT). Subjects were randomized 1:1 between Arm A (P 80 mg/m2 day 1, 8 and 15 q 28 days plus pelareorep 3 x 1010 TCID50 day 1,2,8,9,15,16 q 28 days) and Arm B (P 80 mg/m2 day 1, 8 and 15 q 28 days). Treatment was continued until disease progression (PD) or unacceptable toxicity. Objective response was assessed every 8 weeks. Primary endpoint was progression free survival (PFS). The study had 90% power to detect an improvement of PFS from 4 to 7.5 months (HR 0.5, two-sided α=0.2). All p-values are two-sided. Results: Between July 2012...
1033 Background: MA.32 investigates effects of Metformin vs. Placebo, in addition to standard car... more 1033 Background: MA.32 investigates effects of Metformin vs. Placebo, in addition to standard care, on invasive disease free survival and other outcomes. Metformin may improve obesity and metabolic factors [insulin, glucose, leptin, C-reactive protein (CRP)] that have been associated with poor BC outcomes. Maintaining blinding of investigators to outcomes, we conducted a planned, DSMB approved, analysis of the effect of Metformin vs. Placebo on weight and metabolic factors at 6 months, including examination of interactions with baseline body mass index (BMI), in the first 498 subjects with paired fasting plasma samples. Methods: 498 non-diabetic subjects with T1-3, N0-3, M0 BC meeting defined entry criteria who had completed surgery and adjuvant chemo (if given) provided fasting blood samples at randomization and 6 months (while on study drug). Glucose was measured locally; blood was aliquoted, frozen and stored at -80°C then shipped to NCIC CTG (Kingston, Canada). Paired plasma ali...
The authors describe an unusual variant of alkaline phosphatase (ALP) discovered in a patient wit... more The authors describe an unusual variant of alkaline phosphatase (ALP) discovered in a patient with a 90-fold increase in serum ALP. The variant ALP was indistinguishable from the bone isoenzyme when subjected to chemical inhibition, heat inactivation, lectin precipitation, and routine electrophoresis. However, treatment with neuraminidase produced a marked decrease in the ALP variant's electrophoretic mobility and a reduction in its molecular weight. A bone marrow biopsy revealed metastatic infiltration of the bone marrow by adenocarcinoma of the prostate accompanied by a remarkable amount of new bone formation, suggesting a bone origin for the unusual isoenzyme. The authors believe this to be the first report of an ALP variant with these properties.
542 Background: Met, a drug used to treat type 2 diabetes, is being evaluated as an anti-cancer a... more 542 Background: Met, a drug used to treat type 2 diabetes, is being evaluated as an anti-cancer agent. Long-term use is associated with BCH Vit B12 DEF in up to 30%; a subset may develop symptomatic DEF. It is unknown if Vit B12 DEF is due to diabetes or Met use. We examined Vit B12 DEF in NCIC CTG MA.32, an RCT of adjuvant Met vs Pl in non-diabetic BC patients (pts). Methods: This was a DSMC approved central lab analysis in the first 492 (of 3649) high risk N0/N1-3 BC pts receiving standard therapy randomized onto MA.32 (Met 850 mg bid vs Pl bid for 5 years). VitB12 was analysed in baseline and 6 month (mo) fasting plasma; levels <181 pmol/L were DEF, 181 to 221 pmol/L borderline. Methylmalonic acid (MMA) and homocysteine (HC) (elevated in clinical Vit B12 DEF) were assayed in those with Vit B12 levels <222 pmol/L at either time. Hgb was measured locally. Analysis used Spearman’s rank correlation coefficients and Wilcoxon signed rank test for continuous variables and Chi-square test for 2 by 2 tables. Re...
Background: Pelareorep is a Dearing strain of reovirus serotype 3, with demonstrated in vitro and... more Background: Pelareorep is a Dearing strain of reovirus serotype 3, with demonstrated in vitro and in vivo activity in many cancers and synergistic cytotoxic activity with microtubule targeting agents, including taxanes. This study was designed to determine the efficacy and safety of pelareorep + P compared to P alone in mBC. Materials and Methods: This randomized, open-label, phase II study enrolled subjects who had mBC previously exposed to chemotherapy (CT). Subjects were randomized 1:1 between Arm A (P 80 mg/m2 day 1, 8 and 15 q 28 days plus pelareorep 3 x 1010 TCID50 day 1,2,8,9,15,16 q 28 days) and Arm B (P 80 mg/m2 day 1, 8 and 15 q 28 days). Treatment was continued until disease progression (PD) or unacceptable toxicity. Objective response was assessed every 8 weeks. Primary endpoint was progression free survival (PFS). The study had 90% power to detect an improvement of PFS from 4 to 7.5 months (HR 0.5, two-sided α=0.2). All p-values are two-sided. Results: Between July 2012...
1033 Background: MA.32 investigates effects of Metformin vs. Placebo, in addition to standard car... more 1033 Background: MA.32 investigates effects of Metformin vs. Placebo, in addition to standard care, on invasive disease free survival and other outcomes. Metformin may improve obesity and metabolic factors [insulin, glucose, leptin, C-reactive protein (CRP)] that have been associated with poor BC outcomes. Maintaining blinding of investigators to outcomes, we conducted a planned, DSMB approved, analysis of the effect of Metformin vs. Placebo on weight and metabolic factors at 6 months, including examination of interactions with baseline body mass index (BMI), in the first 498 subjects with paired fasting plasma samples. Methods: 498 non-diabetic subjects with T1-3, N0-3, M0 BC meeting defined entry criteria who had completed surgery and adjuvant chemo (if given) provided fasting blood samples at randomization and 6 months (while on study drug). Glucose was measured locally; blood was aliquoted, frozen and stored at -80°C then shipped to NCIC CTG (Kingston, Canada). Paired plasma ali...
The authors describe an unusual variant of alkaline phosphatase (ALP) discovered in a patient wit... more The authors describe an unusual variant of alkaline phosphatase (ALP) discovered in a patient with a 90-fold increase in serum ALP. The variant ALP was indistinguishable from the bone isoenzyme when subjected to chemical inhibition, heat inactivation, lectin precipitation, and routine electrophoresis. However, treatment with neuraminidase produced a marked decrease in the ALP variant's electrophoretic mobility and a reduction in its molecular weight. A bone marrow biopsy revealed metastatic infiltration of the bone marrow by adenocarcinoma of the prostate accompanied by a remarkable amount of new bone formation, suggesting a bone origin for the unusual isoenzyme. The authors believe this to be the first report of an ALP variant with these properties.
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