Four-year effects of exercise on fatigue and physical activity in patients with cancer

Background: In the earlier randomized controlled Physical Activity during Cancer Treatment (PACT) study, we found beneficial effects of an 18-week supervised exercise program on fatigue in patients with newly diagnosed breast or colon cancer undergoing adjuvant treatment. The present study assessed long-term effects of the exercise program on levels of fatigue and physical activity 4years after participation in the PACT study. Methods: The original study was a two-armed, multicenter randomized controlled trial comparing an 18-week supervised exercise program to usual care among 204 breast cancer patients and 33 colon cancer patients undergoing adjuvant treatment. Of the 237 PACT participants, 197 participants were eligible and approached to participate in the 4-year post-baseline measurements, and 128 patients responded. We assessed fatigue and physical activity levels at 4years post-baseline and compared this to levels at baseline, post-intervention (18weeks post-baseline), and at 36weeks post-baseline. Results: Intention-to-treat mixed linear effects model analyses showed that cancer patients in the intervention group reported significantly higher moderate-to-vigorous total physical activity levels (141.46min/week (95% confidence interval (CI) 1.31, 281.61, effect size (ES)=0.22) after 4years compared to the usual care group. Furthermore, cancer patients in the intervention group tended to experience less physical fatigue at 4years post-baseline compared to the usual care group (-1.13, 95% CI-2.45, 0.20, ES=0.22), although the result was not statistically significant. Conclusion: Patients with breast or colon cancer who participated in the 18-week exercise intervention showed significant higher levels of moderate-to-vigorous total physical activity levels and a tendency towards lower physical fatigue levels 4years post-baseline. Our result indicate that exercising during chemotherapy is a promising strategy for minimizing treatment-related side effects, both short and long term

Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer.

Contains fulltext : 79995.pdf (publisher's version ) (Open Access)BACKGROUND: Fluoropyrimidine-based chemotherapy plus the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab is standard first-line treatment for metastatic colorectal cancer. We studied the effect of adding the anti-epidermal growth factor receptor (EGFR) antibody cetuximab to a combination of capecitabine, oxaliplatin, and bevacizumab for metastatic colorectal cancer. METHODS: We randomly assigned 755 patients with previously untreated metastatic colorectal cancer to capecitabine, oxaliplatin, and bevacizumab (CB regimen, 378 patients) or the same regimen plus weekly cetuximab (CBC regimen, 377 patients). The primary end point was progression-free survival. The mutation status of the KRAS gene was evaluated as a predictor of outcome. RESULTS: The median progression-free survival was 10.7 months in the CB group and 9.4 in the CBC group (P=0.01). Quality-of-life scores were lower in the CBC group. The overall survival and response rates did not differ significantly in the two groups. Treated patients in the CBC group had more grade 3 or 4 adverse events, which were attributed to cetuximab-related adverse cutaneous effects. Patients treated with cetuximab who had tumors bearing a mutated KRAS gene had significantly decreased progression-free survival as compared with cetuximab-treated patients with wild-type-KRAS tumors or patients with mutated-KRAS tumors in the CB group. CONCLUSIONS: The addition of cetuximab to capecitabine, oxaliplatin, and bevacizumab resulted in significantly shorter progression-free survival and inferior quality of life. Mutation status of the KRAS gene was a predictor of outcome in the cetuximab group. (ClinicalTrials.gov number, NCT00208546.

Extended adjuvant aromatase inhibition after sequential endocrine therapy in postmenopausal women with breast cancer:follow-up analysis of the randomised phase 3 DATA trial

Background: The DATA study evaluated the use of two different durations of anastrozole in patients with hormone receptor-positive breast cancer who were disease-free after 2–3 years of tamoxifen. We hereby present the follow-up analysis, which was performed after all patients reached a minimum follow-up of 10 years beyond treatment divergence. Methods: The open-label, randomised, phase 3 DATA study was performed in 79 hospitals in the Netherlands (ClinicalTrials.gov, number NCT00301457). Postmenopausal women with hormone receptor-positive breast cancer who were disease-free after 2–3 years of adjuvant tamoxifen treatment were assigned to either 3 or 6 years of anastrozole (1 mg orally once a day). Randomisation (1:1) was stratified by hormone receptor status, nodal status, HER2 status, and prior tamoxifen duration. The primary outcome was adapted disease-free survival, defined as disease-free survival from 3 years after randomisation onwards. Adapted overall survival was assessed as a secondary outcome. Analyses were performed according to the intention-to-treat design. Findings: Between June 28, 2006, and August 10, 2009, 1912 patients were randomly assigned to 3 years (n = 955) or 6 years (n = 957) of anastrozole. Of these, 1660 patients were eligible and disease-free at 3 years after randomisation. The 10-year adapted disease-free survival was 69.2% (95% CI 55.8–72.3) in the 6-year group (n = 827) and 66.0% (95% CI 62.5–69.2) in the 3-year group (n = 833) (hazard ratio (HR) 0.86; 95% CI 0.72–1.01; p = 0.073). The 10-year adapted overall survival was 80.9% (95% CI 77.9–83.5) in the 6-year group and 79.2% (95% CI 76.2–81.9) in the 3-year group (HR 0.93; 95% CI 0.75–1.16; p = 0.53). Interpretation: Extended aromatase inhibition beyond 5 years of sequential endocrine therapy did not improve the adapted disease-free survival and adapted overall survival of postmenopausal women with hormone receptor-positive breast cancer. Funding: AstraZeneca