Prolonged Response to Regorafenib in a Patient with Iodine Refractory Thyroid Cancer.

Thyroid cancer is the most common type of endocrine malignancy. Cornerstones of thyroid cancer treatment include surgery, radioactive iodine ablation, and thyroid stimulating hormone suppression. The National Comprehensive Cancer Network guidelines recommend two tyrosine kinase inhibitors for thyroid cancer patients who are non-responsive to iodine: sorafenib and lenvatinib. Another oral kinase inhibitor, regorafenib, is not considered standard of care treatment for differentiated thyroid cancer. The chemical structures of regorafenib and sorafenib differ by a single fluorine atom. Given the significant improvement in progression-free survival (PFS) of sorafenib compared to placebo demonstrated in the phase 3 DECISION trial, we report on a patient with iodine-refractory follicular thyroid cancer treated with regorafenib as part of a phase 1 clinical trial. A 75 year old woman was diagnosed with follicular thyroid carcinoma in 2006 and initiated on treatment with regorafenib in 2011. She has completed 76 cycles with stable disease and pulmonary metastases 34% smaller than baseline.

A fishy conclusion regarding n-3 fatty acid supplementation in cancer patients.

Clinical studies are emerging to support providing long chain n-3 fatty acids, found in fish oils, to prevent muscle loss, minimize side effects and improve chemotherapy response in patients with cancer. However, a recent report using experimental models made the concluding statement "..., the use of [fish oil] products during chemotherapy treatment should be avoided". This recommendation is not in line with current understanding of human nutrient requirements and needs to be carefully weighed against evidence supporting fish oil supplementation. The potential clinical detriment of consuming fish oil when undergoing platinum based therapies claimed by Roodhart et al. is not taken within the context of the collective work citing beneficial effects of fish oil in experimental models as well as in humans. Platinum-based therapies are standard of care for lung cancer in many regions of the world with no evidence that they are more or less effective than in countries where oily fish intake is minimal. Overall, the human nutrition recommendations made in the discussion of Roodhart et al. are not supported by the experimental evidence provided in the paper nor within the context of other work in this area.

Nutritional intervention with fish oil provides a benefit over standard of care for weight and skeletal muscle mass in patients with nonsmall cell lung cancer receiving chemotherapy.

BACKGROUND: Involuntary weight loss is a major contributor to mortality and morbidity in patients with advanced cancer. Nutritional intervention with fish oil (FO)-derived eicosapentaenoic acid (EPA) may prevent deterioration of body composition. This study compared intervention with FO with standard of care (SOC; no intervention) with regard to weight, skeletal muscle, and adipose tissue in newly referred patients with nonsmall cell lung cancer from the time of initiation to completion of first-line chemotherapy. METHODS: Forty patients completed the study; there were 16 in the FO group (dose of 2.2 g of EPA/day) and 24 patients in the SOC group. Skeletal muscle and adipose tissue were measured using computed tomography images. Blood was collected and weight was recorded at baseline and throughout chemotherapy. RESULTS: Patients in the SOC group experienced an average weight loss of 2.3 ± 0.9 kg whereas patients receiving FO maintained their weight (0.5 ± 1.0 kg) (P = .05). Patients with the greatest increase in plasma EPA concentration after FO supplementation were found to have the greatest gains in muscle (r(2) = 0.55; P = .01). Approximately 69% of patients in the FO group gained or maintained muscle mass. Comparatively, only 29% of patients in the SOC group maintained muscle mass, and overall the SOC group lost 1 kg of muscle. No difference in total adipose tissue was observed between the 2 groups. CONCLUSIONS: Nutritional intervention with 2.2 g of FO per day appears to provide a benefit over SOC, resulting in the maintenance of weight and muscle mass during chemotherapy.

Supplementation with fish oil increases first-line chemotherapy efficacy in patients with advanced nonsmall cell lung cancer.

BACKGROUND: Palliative chemotherapy is aimed at increasing survival and palliating symptoms. However, the response rate to first-line chemotherapy in patients with nonsmall cell lung cancer (NSCLC) is less than 30%. Experimental studies have shown that supplementation with fish oil (FO) can increase chemotherapy efficacy without negatively affecting nontarget tissue. This study evaluated whether the combination of FO and chemotherapy (carboplatin with vinorelbine or gemcitabine) provided a benefit over standard of care (SOC) on response rate and clinical benefit from chemotherapy in patients with advanced NSCLC. METHODS: Forty-six patients completed the study, n = 31 in the SOC group and n = 15 in the FO group (2.5 g EPA + DHA/day). Response to chemotherapy was determined by clinical examination and imaging. Response rate was defined as the sum of complete response plus partial response, and clinical benefit was defined as the sum of complete response, partial response, and stable disease divided by the number of patients. Toxicities were graded by a nurse before each chemotherapy cycle. Survival was calculated 1 year after study enrollment. RESULTS: Patients in the FO group had an increased response rate and greater clinical benefit compared with the SOC group (60.0% vs 25.8%, P = .008; 80.0% vs 41.9%, P = .02, respectively). The incidence of dose-limiting toxicity did not differ between groups (P = .46). One-year survival tended to be greater in the FO group (60.0% vs 38.7%; P = .15). CONCLUSIONS: Compared with SOC, supplementation with FO results in increased chemotherapy efficacy without affecting the toxicity profile and may contribute to increased survival.

Skeletal muscle depletion is associated with reduced plasma (n-3) fatty acids in non-small cell lung cancer patients.

Upwards of 50% of newly diagnosed advanced lung cancer patients have severe muscle wasting (sarcopenia). Supplementation with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in advanced cancer has been shown to attenuate lean tissue wasting. However, the relationship between muscle mass and plasma (n-3) fatty acids in the absence of supplementation is unclear. We aimed to determine how plasma phospholipid (n-3) fatty acids relate to sarcopenia and change in muscle mass in non-small cell lung cancer patients receiving chemotherapy. Computed tomography images were used to measure muscle mass. Patients were classified as sarcopenic or nonsarcopenic based on sex-specific cutpoints. Change in muscle mass during chemotherapy (2.5 mo) was calculated and patients were divided into quartiles based on the rate of muscle loss or gain. Patients with sarcopenia had lower plasma EPA (16.7 +/- 2.1 micromol/L vs. 31.6 +/- 4.4 micromol/L; P = 0.001), DHA (36.6 +/- 4.0 micromol/L vs. 55.3 +/- 4.0 micromol/L; P = 0.003), and Sigma(n-3) fatty acids (63.6 +/- 5.6 micromol/L vs. 95.0 +/- 7.7 micromol/L; P = 0.002) than nonsarcopenic patients. Patients with maximal muscle loss (mean - 3.5 kg) had lower plasma EPA (12.2 +/- 3.3 micromol/L vs. 35.0 +/- 7.1 micromol/L; P = 0.03), DHA (26.9 +/- 8.7 micromol/L vs. 59.6 +/- 5.3 micromol/L; P = 0.01), and Sigma(n-3) fatty acids (57.8 +/- 13.5 micromol/L vs. 104.6 +/- 11.1 micromol/L; P = 0.005) compared with patients who were gaining muscle (mean +1 kg). Plasma (n-3) fatty acids are depleted in cancer patients with sarcopenia, which may contribute to accelerated rates of muscle loss.