Researchers assess safety, tolerability of exercise in metastatic breast cancer

The Exercise-Oncology Research Program at Memorial Sloan Kettering Cancer Center is designed to assess how exercise can mitigate the cardiovascular side effects of cancer treatment, and prevent or delay cancer development and progression.

The program recently launched an investigation to evaluate the safety and tolerability of exercise in women with advanced breast cancer.

Researchers randomly assigned participants to one of two study arms: standard-of-care cancer treatment plus supervised exercise training, or standard of care plus progressive stretching.

Lee Jones

Safety and tolerability of the exercise training intervention — as well as changes in physical functioning and outcomes, such as participant-reported quality of life and fatigue — will serve as primary outcome measures.

HemOnc Today spoke with Lee Jones, PhD, exercise scientist at Memorial Sloan Kettering Cancer Center and director of the Exercise-Oncology Research Program, about the basis of the trial, how the patient population was selected and how this trial could lay the groundwork for future investigations.

Question: How did this trial come about?

Answer: In general, studies suggest that exercise following a cancer diagnosis is associated with reductions in cancer recurrence and mortality. About 80% of all studies in this field are focused toward using exercise to either help prepare patients for their treatment, to help patients cope with treatment as they are going through it or to help them recover from treatment. Based on these studies, we started to conduct preclinical research to test the biological plausibility that treatment with exercise slows tumor growth. The epidemiological data provide a signal that exercise may be effective, but to prove it requires rigorous scientific testing similar to the development and testing of a new cancer drug. Based on initial positive preclinical data, and because the vast majority of exercise studies to date were performed in patients with early-stage disease, we started our ongoing study to examine the safety and tolerability of exercise. Essentially this would be the phase 1 equivalent study for a behavioral study.

Q: What research preceded yours?

A: This line of investigation has been going on for a few years. This study is an incremental step toward the ultimate goal, which is to test whether exercise inhibits tumor growth in women with breast cancer, and possibly inhibits tumor growth and progression in other types of tumors. Research in this area started about 15 years ago. At the time, there was very little research on exercise in people with cancer. The common advice and dogma at that time was that individuals rest and take it easy after a cancer diagnosis, and that exercise may not be feasible for individuals with cancer. A study by Holmes and colleagues — published in 2005 in JAMA — suggested exercise levels following a diagnosis of early-stage breast cancer were associated with a reduction in the risk of recurrence as well as dying from breast cancer. This was really the first study to show this relationship. Since this time, there have now been several epidemiological studies examining the relationship between self-reported exercise and outcomes in individuals with breast cancer, as well as colorectal and prostate cancer.

Q: Where did you start?

A: The first questions we wanted to test were whether exercise was safe and tolerable, and whether it was associated with changes in patient-reported outcomes — such as quality of life and fatigue — as well as physiological changes in women with early-stage disease following the completion of cancer treatment. Then, we began to examine the safety, tolerability and preliminary effects of exercise in women undergoing treatment for early-stage breast cancer, as well as other cancer types. We know exercise impacts people differently and may not be a viable strategy for all patients, especially because treatment affects patients differently. So, we first wanted to find out whether exercise was safe and which patients were able to tolerate it.

Q: What is the design of the current trial?

A: It is a two-arm randomized, controlled trial that includes 72 women with advanced breast cancer. All women have undergone several baseline assessments, and women are randomly assigned either to standard of care plus exercise training or to standard of care plus progressive stretching. Those in the exercise group come into our facility to exercise 3 days per week for 12 weeks. All exercise is supervised one-on-one by our trained team of exercise physiologists. We want to ensure we are able to adjust or modify the dose of exercise in real time to ensure safety, and this also helps us accurately quantify the dose of exercise that participants are performing. In the stretching group, participants come into our center 3 days per week for 12 weeks. They receive the same one-on-one attention as the women in the aggressive training group, but the form of activity is a little different.

Q: Was there a specific reason for choosing th is patient population?

A: Our study is driven by the fact that we have done a lot of work in early-stage breast cancer. An outcome like disease progression is challenging to test in women with early-stage disease because it would require a very large trial — thousands of patients — with long-term follow-up. Addressing this question in advanced cancer is more feasible.

Q: If this study is successful, what is next?

A: If we find that exercise is safe and tolerable, we will consider designing the next trial to assess whether exercise shows clinical activity in women with advanced breast cancer. In other words, does exercise compare to just standard treatment alone, or does exercise improve disease outcomes in advanced cancer? We are not ready for this step yet, but if our current study is successful, that will be next.

Q: Some physicians are concerned that not all patients with cancer will be able to tolerate rigorous exercise. H ow will the trial account for this ?

A: I certainly agree. Not all patients can exercise. We realize that exercise has drug-like effects, and not all drugs are going to be applicable and appropriate for all patients. So, I definitely would not suggest that all patients start vigorously exercising after they read our work. Every patient included in our studies goes through physiologic testing to make sure that the exercise is safe for that person. The fitness testing includes analysis of their heart. We also get the oncologist’s approval before we approach a patient about the study. We carefully screen women to find those for whom we believe exercise is appropriate. It is important to note that we are not accepting individuals who already exercise; our patient population is considered sedentary to begin with. Anyone who is interested in starting an exercise program should first talk to their physician or oncologist.

Q: Is there anything else that you feel is important to add?

A: Research in this field is still new and we are just getting started. So, there are a lot of questions that still need to be addressed. We are going about this research in the same way we would test a new drug. We are carefully doing the research and making sure our trials are rigorous. There are some hints that exercise may be beneficial, but it is far from proven at this point.

Reference:

Holmes MD, et al. JAMA. 2005;doi:10.1001/jama.293.20.2479.

For more information:

Lee Jones, PhD, can be reached at Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065; email: jonesl3@mskcc.org.

Disclosure: Jones reports no relevant financial disclosures.