Milk and kefir maintain aspects of health during doxorubicin treatment in rats.

Doxorubicin (DOX), a powerful anthracycline antibiotic commonly used to treat a wide variety of cancers, is associated with the production of reactive oxygen species that cause oxidative damage, resulting in cardiac dysfunction. Components of dairy may have protective effects against DOX-induced cardiac damage. Kefir is a naturally fermented milk product containing antioxidants, probiotic bacteria, and yeast in addition to the protective components of dairy. We explored the effects of dietary milk and kefir on DOX-induced cardiotoxicity in rats. We used singly housed, 10-wk-old male Sprague Dawley rats assigned to 1 of 3 isocaloric diets, control (CON n = 24), milk (MLK, n = 24), or kefir (KEF, n = 24), with equivalent macronutrient profiles. After a 9-wk dietary intervention, all animals were given either a bolus injection (15 mg/kg) of DOX (CON-DOX n = 12; MLK-DOX n = 12, KEF-DOX n = 12) or saline (CON-SAL n = 12; MLK-SAL n = 12; KEF-SAL n = 12). Body weight, grip strength, echocardiographic evaluation of cardiac geometry, and cardiac function were evaluated using echocardiography at 5 d postinjection and data were analyzed using ANOVA. Survival at d 5 post-DOX injection was 92 and 100% in KEF-DOX and MLK-DOX, respectively, and 75% in CON-DOX. By the last week of the dietary intervention, and just before injection with saline or DOX, CON weighed significantly (14%) more than the MLK and KEF. The DOX treatment resulted in significant reductions in body weight; however, we found no diet × drug interactions. The DOX treatment reduced peak grip strength compared with SAL; when compared with pre-injection measures, MLK-DOX rats did not experience a significant reduction in peak grip strength compared with CON-DOX and SAL-DOX rats. Heart mass in MLK and KEF was significantly higher when compared with CON. In summary, 9 wk of milk or kefir ingestion resulted in lower body size and higher heart mass after DOX treatment. Additionally, MLK preserved peak grip strength after DOX treatment, whereas KEF or CON did not. We observed no consistent protective effects with respect to heart dimensions and function. These findings suggest that long-term milk or kefir ingestion may be helpful in optimizing health before and during doxorubicin treatment.

Short communication: Sensory analysis of a kefir product designed for active cancer survivors.

Kefir is a fermented milk product that is a good source of protein and health-promoting bacteria. It has the potential to improve recovery from exercise and the health and well-being of cancer survivors. The purpose of this study was to explore cancer survivor attitudes about and acceptance of a kefir recovery beverage made from cultured milk, whole fruit, natural sweeteners, and other natural ingredients. Kefir was made by inoculating and fermenting milk with kefir grains. The kefir was then mixed with a fruit base and given to cancer survivors (n = 52) following a bout of exercise. Participants evaluated the acceptability of the beverage samples (overall appearance, aroma, taste, mouthfeel, and overall liking) using a 9-point hedonic scale, and they evaluated the smoothness using a 3-category just-about-right scale (not enough, just about right, and too much). They also expressed their physical and psychological feelings about the beverage using a 5-point scale (1 = not at all to 5 = extremely) and indicated their purchase intent using a binomial (yes/no) response. The health benefits of kefir were then explained, and participants sampled a second beverage (the same product), answering the same questions related to overall liking, feeling, and intent to purchase. We used a paired Student's t-test to compare beverage liking and emotion scores before and after participants learned about the health benefits of kefir. Data are presented as mean ± standard deviations. The beverage scored significantly higher for overall liking after the health benefits were explained (6.5 ± 1.8 and 7.0 ± 1.7 out of 9 before and after the explanation of health benefits, respectively). Participants showed a high intent to purchase before they learned about the health benefits (75% of participants indicated an intent to purchase, and 89% after they learned about the health benefits). The beverage received high scores overall and, except for an improvement in overall liking, we observed no significant differences in physical and psychological feelings before and after participants learned that it contained kefir and had potential health benefits. We found the beverage to be acceptable for consumption by cancer survivors, and the majority of participants showed an interest in purchasing for after exercise.

A phase I dose-escalation study of aflibercept administered in combination with pemetrexed and cisplatin in patients with advanced solid tumours.

BACKGROUND: To evaluate the safety, pharmacokinetics (PKs), and pharmacodynamics of aflibercept, and to identify the recommended phase II dose (RP2D) of aflibercept in combination with pemetrexed and cisplatin. METHODS: Aflibercept was administered at escalating doses of 2, 4, or 6 mg kg(-1) in combination with fixed doses of pemetrexed (500 mg m(-2)) plus cisplatin (75 mg m(-2)) every 3 weeks. Blood samples were collected for PK analyses. Serum antiaflibercept antibodies were quantified to assess their impact on systemic aflibercept concentrations. RESULTS: Eighteen patients were enrolled. One patient dosed at 4 mg kg(-1) experienced grade 3 hypophosphatemia (dose-limiting toxicity; DLT), which prompted a cohort expansion. No further DLTs were observed in the 4 mg kg(-1) cohort or the 6 mg kg(-1) dose cohort. Most common adverse events (AEs) of all grades included (%): fatigue (89), anaemia (89), nausea (83), hyponatremia (78), and neutropenia (72). Grade ≥ 3 AEs consistent with anti-vascular endothelial growth factor therapy included (%): hypertension (22), pulmonary embolism (11), and deep vein thrombosis (6). Five patients (28%) experienced mild neurocognitive disturbance. No episodes of reversible posterior leukoencephalopathy syndrome (RPLS) were noted. CONCLUSION: The results of this phase I study allowed further evaluation of the combination of aflibercept with pemetrexed and cisplatin in a phase II study. The RP2D of aflibercept was 6 mg kg(-1), to be administered intravenously every 3 weeks in combination with pemetrexed and cisplatin.