INTRODUCTION

Patients with cancer often experience treatment-related side effects that persist well beyond the end of treatment (1). Studies suggest that exercise performed during adjuvant chemotherapy can reduce some of the symptom-related side effects associated with cancer treatments (e.g., pain, fatigue, and nausea) (2,3). For many patients with cancer who undergo chemotherapy, it is difficult to begin or maintain regular exercise (4). Overall physical activity is reduced by 10% to 20% in patients with breast cancer while receiving chemotherapy (5,6). This reduction is greater in patients engaged in regular exercise prior to beginning treatment (7). Furthermore, a reduction in physical activity can exacerbate some of the symptoms commonly associated with chemotherapy.

A potential approach to promote exercise in patients with cancer is to provide supervised exercise training during treatment (i.e., chemotherapy session). This is similar to the implementation of exercise while undergoing a dialysis treatment session that has been used in patients with end-stage renal failure (8). This strategy is effective for enhancing adherence and improving cardiovascular and psychosocial outcomes (9).

Although several aspects of chemotherapy infusion are similar to that of hemodialysis, sufficient differences exist which warrants examining the feasibility and potential safety of exercise during infusion care. The purpose of this pilot study is to describe the physiological response to a low level, short duration exercise program administered during chemotherapy infusion in a group of patients with breast cancer enrolled in the Exercise and Cancer Integrative Therapy Education (ExCITE) trial. The overall aim of the ExCITE trial was to evaluate the feasibility of incorporating exercise and other healthy lifestyle behaviors in patients with cancer from the time of diagnosis to 1 year beyond the completion of treatment. For this brief report, in addition to describing the physiological response to infusion exercise, we report the frequency of clinically meaningful events occurring following chemotherapy sessions.

METHODS

Women with stage I to III breast cancer were recruited to participate in the ExCITE trial at Henry Ford Hospital (Table 1). Those who enrolled in the study were also invited to perform their exercise sessions during chemotherapy infusion. The selection of participants to perform the infusion exercise was limited by the availability of staff to supervise the exercise sessions. Exercise during infusion was in addition to the other exercise that all subjects were asked to engage in as part of the ExCITE study. Briefly that exercise consisted of 2 to 3 days per week of facility-based supervised exercise performed on both aerobic machines (e.g., treadmill, cycle, etc.) and strength machines (e.g., chest press, leg extension, etc.). Prior to beginning, exercise training subjects performed a cardiopulmonary exercise stress test to quantify cardiorespiratory function, peak heart rate, and ensure exercise safety. Informed consent was obtained from all subjects, and the protocol was approved through The Henry Ford Health System Institutional Review Board prior to study commencement.

TABLE 1. Baseline characteristics of patients.

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Adverse Outcomes

To assess safety of the exercise infusion sessions, the frequency of adverse events during and 3 weeks following the exercise infusion sessions were compared to the events recorded following infusion-only sessions. Data was abstracted, by a clinical research nurse who was blinded to the type of session (i.e., exercise-infusion vs. infusion only). Events were deemed clinically meaningful if there was documentation in the medical record by a physician, nurse, or emergency department visit (Table 2). A Pearson χ² test was used to determine differences between exercise-infusion sessions and infusion-only sessions. Alpha level was set at 0.05.

TABLE 2. Documented adverse events during adjuvant chemotherapy.

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RESULTS

From the initial 14 subjects invited, 5 participated in a total of 17 combined exercise and chemotherapy infusion sessions (range 1 to 6 exercise sessions). Mean exercise duration was 16.4 ± 6.2 minutes, (range of 10 to 20 minutes). The average rating of perceived exertion was 10 ± 1 (between very light and fairly light). Average cycle resistance was 18 ± 6 Watts, and a mean exercise heart rate of 24 beats above rest (~31% of heart rate reserve). No adverse events were noted during the exercise sessions.

In the period following the exercise infusion sessions and before the next infusion session, 2 (12%) adverse clinical events were documented in the medical records. These included an emergency department visit for febrile neutropenia, and a newly reported oropharyngeal candidiasis. Conversely following the 59 non-exercise infusion sessions there were 31 (53%) documented adverse events, including 7 visits to the emergency department (Table 2). The event rate between infusion exercise and infusion only sessions were significantly different (P = 0.003). The length between chemotherapy infusion sessions ranged between 2 to 5 weeks. No differences were found between exercise-infusion sessions, and subsequent changes in either hemoglobin (10.2 vs. 10.7 g·dL⁻¹) or neutrophil counts (6500 vs. 5500 mL⁻¹).

DISCUSSION

This pilot study is one of the first to describe the exercise response during chemotherapy infusion. All 17 exercise sessions were tolerated well, with no concurrent adverse events and appropriate physiological responses to the light intensity exercise. These findings were similar to Thomas et al., who also had patients perform 20 minutes of a cycle ergometer during chemotherapy infusion, reporting good tolerance to the exercise and less boredom than those who did not (10).

In the 2 to 5 week period between infusion sessions (varied by individual patient) we observed significantly fewer reported adverse clinical events following exercise infusion sessions as compared to the nonexercise infusion sessions. The reason for this difference is unclear. Although we did not see a difference in hematological markers, the low statistical power cannot completely rule out this possibility.

Exercise has clearly demonstrated a positive psychological effect for different cancer populations both during and following treatment (1,3,11–16). To promote regular exercise in this population, it is important to advocate its benefits and to find methods to avoid common barriers. Beyond the common physical barriers due to the side effects of chemotherapy (i.e., fatigue and pain), patients report other obstacles including insufficient time, limited access to facilities, and comorbid conditions (10,17,18).

The subjects who participated in the infusion sessions expressed enjoyment in performing the exercise and felt it was a good distraction during an otherwise stressful event. While not measured, it is possible that the exercise sessions were associated with lower clinical events because the subjects experienced less anxiety toward their treatment and thus were less likely to contact their oncology team with complaints.

Because not all subjects participated in the exercise infusion, there is the potential for selection bias. Another potential confounder was the lack of control for the number of ExCITE trial outpatient (on noninfusion days) exercise sessions patients participated in between infusions. Finally, although not statistically significant, the 5 individuals who undertook exercise during infusion were younger, had a higher peak Vo₂, and had a lower BMI than the other 9 ExCITE trial participants who chose not to perform exercise during infusion. However, when analyzing exercise infusion versus nonexercise infusion sessions within those 5 individuals who participated, there was a significant difference in the number of reported subsequent events (exercise = 2/17 vs. nonexercise = 7/15; P = 0.028).

CONCLUSION

While we acknowledge that the small sample size and lack of randomization limits our ability to make any definitive statements, the observed trends are hypothesis generating and warrant further investigation. Appropriately powered, randomized, prospective studies are needed to fully answer the question about safety and efficacy. In addition to the reporting about adverse events, the inclusion of quality of life questionnaires and patient reported outcome measures in future studies will help to determine the use of this novel exercise regimen. Our study suggests that light-intensity exercise performed during chemotherapy infusion sessions appears to be well tolerated in this selected group of patients undergoing treatment for breast cancer.