5/5/15

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A supervised, moderate to high-intensity exercise program in breast cancer patients helped stave off expected declines in fitness and function during adjuvant chemotherapy and improved treatment tolerance, according to randomized trial results.

Patients enrolled in two exercise programs, Onco-Move and OnTrack, saw less decline in cardiorespiratory fitness (P<0.001), better physical functioning (P<0.001), less nausea and vomiting (P<0.029 and P<0.031, respectively), and less pain (P<0.003 andP<0.011, respectively) compared with usual care, reported Hanna van Waart, MD, of the Netherlands Cancer Institute in Amsterdam, and colleagues.

Onco-Move is a low-intensity, home-based physical activity program while OnTrack is a moderate to high-intensity, combined supervised resistance and aerobic exercise, the authors wrote in the Journal of Clinical Oncology (JCO).

In a separate JCO review article, Erin Van Blarigan, ScD, of University of California San Francisco, and Jeffrey Meyerhardt, MD, MPH, of the Dana-Farber Cancer Institute in Boston, summarized the evidence on physical activity and diet after colorectal cancer diagnosis with regard to quality of life, disease recurrence, and survival.

Exercise and Breast Cancer

The Physical Exercise during Adjuvant Chemotherapy Effectiveness Study (PACES) was a randomized, controlled multicenter trial with two intervention groups and a usual care control group.

Most participants had stage II or III breast cancer. Approximately 75% of study participants underwent breast-conserving surgery and approximately the same number received radiotherapy.

Both interventions started with the first cycle of chemotherapy and continued until 3 weeks after the last cycle, the authors explained.

In Onco-Move, participants were urged to engage in at least 30 minutes of physical activity per day, 5 days per week, with an intensity level of 12 to 14 on the Borg Scale of perceived exertion. OnTrack participants were supervised by a physical therapist and trained six large muscle groups for 20 minutes per session, with two series of eight repetitions at 80% of the one repetition maximum.

“On average, participants in OnTrack attended 71% of the planned sessions, while on the basis of the exercise diary, 48% of the OnTrack group and 55% of the Onco-Move group followed recommendations regarding daily activity at least 75% of the time,” the authors noted.

Among 230 patients scheduled to undergo adjuvant chemotherapy, those randomized to the moderate to high-intensity supervised OnTrack program had significantly longer mean endurance times at the end of chemotherapy at 8 minutes compared with usual care, while those randomized to the Onco-Move program had a mean of 4 minutes longer endurance time compared with usual care at the same endpoint.

The effect size between the OnTrack group and the usual care group of 0.90 was considered large while the effective size of 0.45 seen between the Onco-Move and usual care group at 0.45 was considered moderate but clinically relevant, the authors pointed out.

Muscle strength of the arms and legs was also significantly greater in the OnTrack group than in both the usual care and Onco-Move groups, they reported.

On completion of chemotherapy, OnTrack participants also reported significantly less physical and general fatigue, lesser amounts of reduced activity and motivation than usual care patients, and significantly less physical fatigue than participants in the Onco-Move program. Again, the effect sizes of the differences between groups in each of these endpoints ranged from small to moderate.

Both exercise groups reported better physical function on completion of chemotherapy at moderate to large effect sizes, less nausea and vomiting at large effect sizes, and less pain at moderate effect sizes than the usual care group.

Furthermore, the OnTrack group reported significantly better cognitive functioning at a moderate effect size than the usual care group, and less constipation at large effect sizes compared with the two other randomized groups.

Dose Adjustments

A significantly smaller percentage of the OnTrack patients (12%) required dose adjustments in their chemotherapy regimen versus usual care patients (34%) or the Onco-Move group (34%) for an odds ratio of 0.26 (P=0.002).

Patients who participated in the OnTrack program had about a four-fold lower likelihood of requiring a dose adjustment than the other two groups (95% CI 0.1-0.61 for both comparisons), the authors noted.

The average dose reduction among participants in both exercise groups was 10% compared with 25% in the usual care group (95% CI -2.96 to -0.01, P=0.014).

Interestingly, only 6% of patients in the OnTrack exercise program required delay or discontinuation of trastuzumab (Herceptin) because of reduced left ventricular ejection fraction compared with 28% in the usual care group (OR 0.16, 95% CI 0.02-1.57) and 24% in the Onco-Move program (OR 0.20, 95% CI 0.02-1.91).

However, the authors cautioned that the finding is a trend and “based on exploratory analyses … we cannot rule out that our observed differences may reflect a chance finding.”

Six months after completion of chemotherapy, “no significant between-group differences were observed for any of the performance-based measures of physical fitness or in self-reported fatigue,” the authors wrote. “[So while] the observed intervention effects did not reflect an improvement in physical fitness levels or fatigue during chemotherapy, [the effects did reflect] a less step decline or a stable situation.”

On completion of chemotherapy, 34% of patients in the OnTrack program and 40% of those in the Onco-Move program were working compared with 15% of usual care patients (P=0.010).

At 6 months, both exercise groups again had significantly higher return to work rates at approximately 80% compared with 61% of patients in the usual care group (P=0.012).

Physical health limitations were reported by 41% of the usual care group as the reason for not returning to work compared to approximately 25% of patients in the OnTrack and Onco-Move programs.

The limitations of the study included an inability to determine peak oxygen uptake directly as a result of limited testing facilities and the fact that the study was limited to the effect of exercise during adjuvant chemotherapy.

Also, slightly more than half of patients who were potentially eligible for the study declined to participate, raising an issue regarding the generalizability of results to a larger target population.

Nevertheless, “our findings indicate that both a moderate to high-intensity physical exercise program and a low-intensity physical activity program are safe and feasible during adjuvant chemotherapy for breast cancer,” the authors stated. “In general, we would recommend that women who are able and willing to participate be offered a supervised moderate to high-intensity exercise program during adjuvant chemotherapy.”

The authors noted that they had intended to recruit breast and colon cancer patients into the PACES study, but they were unsuccessful because more colon cancer patients received palliative chemotherapy rather than adjuvant treatment.

Also, colon cancer patients who had undergone major abdominal surgery were typically advised to refrain from intense physical activity for 6 weeks after surgery so clinicians were more hesitant to refer patients with colon cancer to the study, they said.

Exercise and Colon Cancer

Van Blarigan and Meyerhardt proposed a series of recommendations for patients with colon cancer based on their review of the literature as well as recommendations from several organization including the American Cancer Society.

These recommendations include:

• Perform at least 150 minutes per week of aerobic activity (brisk walking). Every bout of activity lasting 10 minutes or longer counts towards the weekly goal.
• If 150 minutes of aerobic activity per week is not feasible, patients should aim to be as physically active as possible.
• Perform muscle-strengthening exercise at least 2 days per week if not more.
• Minimize sedentary behavior; if sitting must take place for extended periods of time, frequent short breaks to stand up, stretch, and walk around should be incorporated.
• Limit consumption of refined carbohydrates and foods with a high glycemic index.
• Do not consume sugar-sweetened beverages.

“In conclusion, observational data strongly support a beneficial effect of physical activity after colorectal cancer diagnosis on cancer-specific and overall survival, and the ongoing CHALLENGE (Colon Health and Life-Long Exercise Change) trial is designed to determine whether supervised exercise lengthens survival among patients with high-risk stage II or III colon cancer,” they wrote.

• Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College and Dorothy Caputo, MA, BSN, RN, Nurse Planner

last updated 05.06.2015