Background
Repurposed memantine, mefloquine, and metformin have putative anticancer activity. The objective of this phase 1 study was to determine the maximum tolerated doses (MTDs) of combinations ...of these agents with temozolomide (TMZ).
Methods
Adults with newly diagnosed glioblastoma who completed chemoradiation were eligible. The patients were assigned to receive doublet, triplet, or quadruplet therapy with TMZ combined with mefloquine, memantine, and/or metformin. Dose‐limiting toxicities (DLTs) were determined, using a 3 + 3 study design.
Results
Of 85 enrolled patients, 4 did not complete cycle 1 (the DLT observation period) for nontoxicity reasons, and 81 were evaluable for DLT. The MTDs for doublet therapy were memantine 20 mg twice daily, mefloquine 250 mg 3 times weekly, and metformin 850 mg twice daily. For triplet therapy, the MTDs were memantine 10 mg twice daily, mefloquine 250 mg 3 times weekly, and metformin 850 mg twice daily. For quadruplet therapy, the MTDs were memantine 10 mg twice daily, mefloquine 250 mg 3 times weekly, and metformin 500 mg twice daily. DLTs included dizziness (memantine) and gastrointestinal effects (metformin). Lymphopenia was the most common adverse event (66%). From study entry, the median survival was 21 months, and the 2‐year survival rate was 43%.
Conclusions
Memantine, mefloquine, and metformin can be combined safely with TMZ in patients with newly diagnosed glioblastoma.
Memantine, mefloquine, and metformin can be combined safely with temozolomide in patients with glioblastoma. The maximum tolerated doses determined by this study can be used in future phase 2 clinical trials.
Bevacizumab (BEV) is commonly used for treating recurrent glioblastoma (GBM), and wound healing is a well-established adverse event. Retrospective analysis of GBM patients with and without wound ...healing complications while on BEV treatment is reported. 287 patients identified, majority were males (60 %) with median age of 52.5 years. 14 cases identified with wound healing problems, related to either craniotomy (n = 8) or other soft tissue wounds (n = 6). Median duration of BEV treatment to complication was 62 days (range 6–559). Majority received 10 mg/kg (n = 11) and nine (64.3 %) were on corticosteroids, with median daily dose of 6 mg (range 1–16 mg) for median of 473 days before starting BEV. For dehisced craniotomy wounds, median time for starting BEV from last surgery was 29 days (range 27–345). Median time from starting BEV to developing wound complication was 47 days (range 16–173). Seven (87.5 %) had infected wounds requiring antibiotics, hospitalization. Four (50 %) required plastic surgery. BEV stopped and safely resumed in 6 (75 %) patients; median delay was 70 days (range 34–346). Soft tissue wounds included decubitus ulcer, dehisced striae, herpes simplex, trauma to hand and back, and abscess. Median time from starting BEV to wound issues was 72 days (range 6–559). Five (83.3 %) were infected, requiring antibiotics. While three (50 %) required hospitalization, none required plastic surgery. Treatment stopped in five (83.3 %) and restarted in two (median delay 48 days, range 26–69). Wound healing complications are uncommon but associated with significant morbidity. Identifying those at risk and contributing factors warrants further investigation.
The move must be approved by voters, and the measure could be put on the ballot by the Town Board or petitions filed by residents. email: bobrien@buffnews.com Credit: The Buffalo News, N.Y.
The board scheduled the public hearing on the budget for Nov. 7, and it expects to adopt the budget at its work session the following week, Nov. 14. email: bobrien@buffnews.com Credit: The Buffalo ...News, N.Y.
If the budget package is approved, it will be the third consecutive year without a town tax rate increase. Because of the downturn in the stock market, the town must contribute $416,000 more than ...this year to the state retirement fund for its employees, he said.
Objective To identify and compare the presence of coronary heart disease (CHD) risk factors among 14- and 15-year-old boys and girls.
Design For this cross-sectional study of 54 subjects, a blood ...sample taken after subjects fasted was used to determine total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride concentrations. Dietary intake was estimated using a 24-hour recall and a 2-day food record. Height, weight, and skinfold thicknesses were measured to identify obese and severely obese subjects. Cardiovascular fitness, blood pressure, and cigarette use also were measured. TC, HDL-C, LDL-C, fitness, blood pressure, and smoking are modifiable risk factors for CHD.
Subjects Adolescents were selected by random sampling from lists of students attending public schools in two central Texas cities. Adolescents who were 14 or 15 years old; were not pregnant; and had no history of high blood pressure, diabetes, or heart disease were eligible to participate.
Statistical methods Data were analyzed using Student's t and χ
2 tests.
Results Of the subjects, 25% demonstrated two or more risk factors for CHD. A significantly higher percentage of girls than boys had a TC concentration greater than 5.2 mmol/L. Boys (n=29) had a mean fitness score that indicated a higher level of cardiovascular fitness than girls (n=25); however, the mean score for both groups was below average.
Conclusion Data provide support for increased interventions targeted toward lowering the risk factors for CHD and other chronic diseases in adolescents.
J Am Diet Assoc. 1996; 96:238-242.
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