Measuring Oncological Value of Exercise and Statin

Despite the marked differences between different malignancies' genetic, metabolic, and prognostic factors, hypoxia and adaptation of metabolic changes favoring hypoxic microenvironment are common factors in most solid tumors. Hypoxic microenvironment provides cancer cells multiple advantages: protection from immune system, somatic mutations leading to more aggressive form of cancer, and cancer cells that are adjusted to hypoxic conditions are more prone to form metastases. One possible mechanism for cancer cell to adjust to hypoxic microenvironment is related to lipid metabolism; lipids are known to accumulate into cancer cells in many cancer types. One of the most promising ways to reduce hypoxia in solid tumors is to increase physical exercise. Furthermore, tumors' lipid metabolism can be affected by treatment with cholesterol-lowering statins, which decreases serum cholesterol levels and inhibits cancer cells' own lipid synthesis. The aim of this randomized clinical trial is to investigate if supervised group exercise will improve response to cancer drug treatment in metastasized breast, kidney, prostate, and ovarian cancer compared to unsupervised exercise. The investigators will also evaluate if atorvastatin treatment in combination with guided group exercise can promote even better treatment responses than exercise alone. Exercise program includes aerobic and resistance training. This study is a randomized phase III study testing the research hypothesis for the first time in humans. A total of 240 cancer patients (n=60/cancer type) will be recruited into the study and randomized 1:1:1 into three different groups, i.e. 20 people in each group from each cancer type: 1. 3 months of supervised group exercise 2. 3 months of supervised group exercise and at the same time atorvastatin 40 mg/day 3. to a control group that exercises voluntarily without guidance. In addition, as a separate group, a total of 160 cancer patients (40/cancer type) who are already using statin medication will be recruited for the study and randomized 1:1 into two groups: 1) 3 months of supervised group exercise and 2) independent exercise (a control group that exercises voluntarily without guidance). Before the study begins, the patients are informed orally and in writing about the study. The patients who agree to participate in the study sign an informed consent. The patient follow-up time in each group is two years in 3 months intervals (first visit and 8 follow-up visits) in conjunction with standard cancer treatment follow-up visits. Blood and urine samples and questionnaire data are collected at baseline and at each follow-up visit. Body composition and physical performance are measured at baseline and twice after the intervention. Patients QoL and experiences of exercise are measured in qualitative interviews (in the group participating the qualitative sub-study). The main response variables are 1. cancer progression during cancer treatment based on imaging, symptoms or laboratory findings and 2. mortality of the patients. The other variables of interest in this study are: 3. Hypoxia markers 4. Tolerability of treatment 5. Body composition 6. Physical performance 7. The extent of hypoxia, as measured by PET scans, in participants of the sub-study 4\) Quality of life, perceived pain, depressive symptoms, nutrition and relationships. Adverse events from cancer treatment and treatment interruptions are also monitored.