A diet rich in fish oil and Leucine Ameliorates Hypercalcemia in tumour-induced cachectic mice

Background: Dietary supplementation with leucine and fish oil rich in omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) has previously been shown to reduce cachexia-related outcomes in C26 tumour-bearing mice. To further explore associated processes and mechanisms we investigated changes in plasma Ca2+ levels, the involvement of parathyroid hormone related protein (PTHrP), and its possible interactions with cyclooxygenase 2 (COX-2). Methods: CD2F1 mice were subcutaneously inoculated with C26 adenocarcinoma cells or sham treated and divided in: (1) controls, (2) tumour-bearing controls, and (3) tumour-bearing receiving experimental diets. After 20 days, body and organ masses and total plasma Ca2+ levels were determined. Furthermore, effects of DHA, EPA and leucine on production of PTHrP were studied in cultured C26 cells. Results: The combination of leucine and fish oil reduced tumour-associated hypercalcemia. Plasma Ca2+ levels negatively correlated with carcass mass and multiple organ masses. DHA was able to reduce PTHrP production by C26 cells in vitro. Results indicate that this effect occurred independently of COX-2 inhibition. Conclusion: Our results suggest that cancer-related hypercalcemia may be ameliorated by a nutritional intervention rich in leucine and fish oil. The effect of fish oil possibly relates to a DHA-induced reduction of PTHrP excretion by the tumour

Side‐effects related to adjuvant CAPOX treatment for colorectal cancer are associated with intermuscular fat area, not with total skeletal muscle or fat, a retrospective observational study

Abstract Aims Chemotherapeutic treatment is regularly accompanied by side‐effects. Hydrophilic chemotherapeutics such as capecitabine and oxaliplatin (CAPOX), often used in colorectal cancer treatment, predominantly accumulate in non‐adipose tissues. Therefore the aim of this paper was to investigate whether body composition and fat infiltration in the muscle (muscle attenuation and intermuscular‐adipose‐tissue [IMAT] content) are associated with chemotherapy‐induced toxicities. Methods In this retrospective observational study, we collected data from 115 colorectal cancer patients receiving adjuvant CAPOX chemotherapy between 2006 and 2015. Information on cancer characteristics were obtained from the Netherlands Cancer Registry. Diagnostic CT scans were retrieved to assess cross‐sectional areas of skeletal muscle and adipose tissue at the third lumbar vertebrae. Information on dose‐limiting toxicity [DLT] and relative administered dose (as % of BSA‐based‐planned‐dose) were retrieved from medical charts. Associations between body composition, muscle quality and chemotherapy‐induced toxicities were determined using Cox‐regression and linear‐regression analyses. Results We found that DLT incidence was 90% in our cohort: 50% had their dose reduced, 30% their next cycle postponed, 4% a full treatment stop and 6% was hospitalized at their first DLT. Most common were reductions in oxaliplatin dose whilst keeping the capecitabine dose constant. Cox regression analysis indicated no association between body composition or muscle quality and DLT during the first treatment cycle or time to the first DLT. Multiple linear regression showed that higher IMAT‐index and IMAT muscle percentage were associated with a lower relative administered dose of oxaliplatin. Conclusions In conclusion; only IMAT, not skeletal or fat area was associated with dose‐limiting toxicities among these CRC patients who received CAPOX treatment