Table 4.
Randomized controlled trials with biomarker endpoints of physical activity interventions in cancer survivors*
| First author (reference), year, country | Sample characteristics | Primary endpoint | Intervention arm | Control arm | Attrition and adherence rates and method of adherence measurement | Results and adjustment or stratification |
| Studies of breast cancer survivors | ||||||
| Fairey (54), 2003, Canada; Fairey (55), 2005, Canada; Fairey (56), 2005, Canada | 53 women; mean age 59 y; race or ethnicity NR; diagnosed 1999–2000 | Quality of life | Aerobic (cycling) exercise program; intensity VO2 max = 70%–75%; 3 times/wk, 15 weeks, 15–35 min/session; at least 6 mo after primary treatment; ± hormonal therapy | The control group did not participate in any exercise program and was asked not to begin a structured exercise program | Attrition: 4.2%; Adherence: 98.4%; Monitored by exercise physiologist | Statistically significant differences between groups were observed for changes in IGF-1 (P = .045), IGFBP-3 (P = .021), IGF:IGFBP-3 molar ratio (P = .017), percent-specific lysis of a target natural killer cell at all five effector-to-target ratios (P < .05 for all), the lytic activity per cell (P = .035), and unstimulated [3H]thymidine uptake by peripheral blood lymphocytes (P =.007). No statistically significant differences between groups were observed for change in insulin (P = .941), glucose (P = .824), insulin resistance index (P = .247), or CRP (P = .066). |
| Schmitz (57), 2005, United States | 81 women; mean age 53 y; race or ethnicity NR; diagnosed 2000–2002 | Body fat percentage and lean body mass | Progressive weight training exercise intervention; progressive individualized intensity; twice weekly for 6 mo (for RCT outcomes), 60 min/session; initiated at least 4 mo after primary treatment; ± hormonal therapy | Delayed treatment group | Attrition: NR; Adherence: 80%; Exercise log monitored by fitness trainer | Statistically significant differences between groups were observed for changes in IGF-II (P = .02); No statistically significant differences between groups were observed for change in insulin (P = .79), glucose (P = .90), HOMA (P = 1.00), IGF-I (P = .16), IGFBP-1 (P = .36), IGFBP-2 (P = .30), or IGFBP-3 (P = .32). |
| Ligibel (58), 2008, United States | 101 women; mean age 52 y; race or ethnicity NR; treatment 2004–2006 | Fasting insulin level | Mixed strength and endurance exercise intervention; moderate intensity; 50-min strength training and 90-min aerobic exercise/wk for 16 wk; after primary treatment; ± hormonal therapy | Received routine care for 16 wk | Attrition: 17.8%; Adherence: 73%; Exercise journal reviewed by exercise physiologist | No statistically significant differences between groups were observed for insulin (P = .07), glucose (P = .47), or HOMA (P = .09). |
| Payne (59), 2008, United States | 20 women; mean age 65 y; predominantly white | Neuroendocrine-based serum levels of metabolic regulatory hormones | Walking; moderate intensity; 20 min, four times/wk for 14 wks; after treatment; on hormonal therapy | Usual care, defined as standard interaction with nurses, physicians, and staff | Attrition: 20%; Adherence: NR; Exercise log reviewed by study staff | Statistically significant differences between groups were observed for serotonin (P = .009). No statistically significant differences between groups were observed for cortisol (P = .19), IL-6 (P = NR), or bilirubin (P = .09) |
| Irwin (60), 2009, United States | 75 women; mean age 56 y; predominantly non-Hispanic white; mean time since diagnosis 3.3 y | Fasting insulin level | Aerobic exercise group program; moderate intensity; 150 min/wk for 6 mo; after primary treatment; ± hormonal therapy | Women in the usual care group were instructed to continue with their usual activities | Attrition: NR; Adherence: 73%; Exercise and heart rate log reviewed by exercise physiologist | Statistically significant differences between groups were observed for IGFBP-3 (P = .006) and IGF-1 (P = .026). No statistically significant differences between groups were observed for insulin (P = .089). |
| Studies of colorectal cancer survivors | ||||||
| Allgayer (61), 2004, Germany | 23 men and women; mean age 49 y (intervention arm); race or ethnicity NR; at least 4 wk after primary treatment | Biomarkers of the pro- and anti-inflammatory response | Aerobic exercise; specific type NR; moderate intensity aerobic exercise (55%–65% aerobic power); 40 min/d every d for 2 wk; after primary treatment | Low-intensity exercise program (30%–40% aerobic power); 40 min/d every day for 2 wk | Attrition: NR; Adherence: NR; ECG monitored | Statistically significant differences between groups in median values were observed for IL-1ra (P < .05), a purported measure of anti-inflammatory response, and for two purported measures of the ratios of anti- to pro-inflammatory responses reported as the molar ratios of IL-1ra to IL-6 (P < .05), and of IL1ra to IL-1 (P < .05). No statistically significant differences between groups were observed for circulating cytokines (P value NR) and antagonists (P value NR). Median rather than mean values were reported. The LPS-stimulated IL-1ra response (a purported measure of increased anti-inflammatory response) in the moderate intensity exercise group decreased from 31 532.6 (95% CI = 160.0 to 70 028.0 pg/mL) to 22 892.0 pg/mL (95% CI = 6376.0 to 34 726.0 pg/mL) after 2 wk (P < .05). In contrast, in the low- intensity exercise group, LPS-stimulated cytokines, and antagonists did not change statistically significantly during exercise. Circulating cytokines and antagonists remained unchanged in both groups. |
| Allgayer (62), 2008, Germany | 49 men and women; mean age 58 y; race or ethnicity NR | Oxidative DNA damage | Maximal individual aerobic exercise program; high-intensity (0.5–0.6 × maximal exercise capacity); 30–40 min/d for 2 wk; after primary treatment | Moderate intensity aerobic exercise (0.3–0.4 × maximal exercise capacity) | Attrition: NR; Adherence: NR; ECG monitored | Statistically significant differences between groups were observed for urinary 8-oxo-dG (P = .02). Median rather than mean values were reported. Moderate intensity exercise statistically significantly reduced urinary 8-oxo-dG excretion levels from 8.47 ± 1.99 to 5.81 ± 1.45 (in ng/mg creatinine, mean ± SE, P = .02), suggesting decreased oxidative DNA damage, whereas high-intensity exercise resulted in a non-statistically significant increase from 5.00 ± 1.31 to 7.11 ± 1.63 (in ng/mg creatinine, P = .18). |
| Studies of gastric cancer survivors | ||||||
| Na (63), 2000, Korea | 35 men and women; mean age 57.8 y (intervention arm); race or ethnicity NR | Natural killer cell cytotoxic activity | Range of motion and strength exercises in bed immediately after surgery, progressing to arm and bicycle ergometer beginning on day 2 after surgery for 14 d, 30 min/d; intensity 60% of maximal heart rate; 2 times/d, 5 times/wk; after surgery | No exercise | Attrition: NR; Adherence: NR; Supervised activity | Statistically significant difference between groups was observed for mean natural killer cell cytotoxic activity (P < .05). |
| Studies of prostate cancer survivors | ||||||
| Segal (64), 2003, Canada | 155 men; mean age 68 y; race or ethnicity NR; 2 y after diagnosis | Fatigue and disease-specific quality of life | Resistance exercise training; 60%–70% of one-RM intensity; 3 times/wk for 12 wk; during treatment (ADT) | Offered exercise advice after intervention arm completed 12-wk training | Attrition: 12.9%; Adherence: 79%; Supervised activity | No statistically significant differences between groups were observed for PSA (P = .31) and testosterone (P = .24). |
| Segal (65), 2009, Canada | 121 men; mean age 66 y; race or ethnicity NR | Fatigue | Resistance or aerobic exercise program; resistance training, 8–12 repetitions: 60%–70% 1 RM; aerobic training to 70%–75% peak VO2 progressing 15–45 min/wk for 24 wks; during treatment (radiotherapy) | Usual care participants were asked not to initiate exercise and were offered a program after the intervention arm completed all assessments | Attrition: 7.4%; Adherence: 88%; Supervised activity | No statistically significant differences between groups were observed for PSA (P = .181), testosterone (P = .728), and hemoglobin (P = .437). |
| Galvao (66), 2009, Australia | 57 men; mean age 69.5 y (intervention arm); race or ethnicity NR | Whole body and regional lean mass | Combined resistance exercise program; resistance training (12- to 6-RM) for two to four sets per exercise and aerobic training (15–20 min of cardiovascular exercises at 65%–80% maximum heart rate); twice/wk for 12 wk; during treatment (ADT) | Usual care | Attrition: 1.8%; Adherence: 94%; Supervised activity | Statistically significant differences between groups were observed for CRP (P = .008). No statistically significant differences between groups were observed for testosterone (P = .139), PSA (P = .690), cholesterol (P t = .711), triglycerides (P = .951), insulin (P = .435), and homocysteine (P = .597). |
*
ADT = androgen deprivation therapy; BMI = body mass index; CI = confidence interval; CRP = C-reactive protein; ECG = electrocardiography; HOMA = homeostasis model assessment; IGF = insulinlike growth factor; IGFBP = insulinlike growth factor binding protein; LPS = lipopolysaccharide; NR = not reported; PSA = prostate-specific antigen; RM = repetition maximum; SAA = serum amyloid A; VO2 = aerobic capacity.