Effect of home-based resistance training on chemotherapy relative dose intensity and tolerability in colon cancer: The FORCE randomized control trial

Abstract

Background: Many patients with colon cancer cannot fully adhere to postoperative chemotherapy due to dose-limiting toxicities, resulting in lower relative dose intensity (RDI) and potentially compromising overall survival. This study examined whether home-based resistance training (RT) during adjuvant chemotherapy improves RDI and patient-reported toxicities versus usual care (UC) in colon cancer patients.

Methods: Multicenter, randomized control trial (RCT) conducted at community and academic practices. Enrollment of patients receiving postoperative chemotherapy for colon cancer occurred between February 23, 2018, and September 29, 2021; final follow-up was March 21, 2022. Participants were randomized to RT (n = 90) or UC (n = 91) for the duration of chemotherapy. Participants in the RT group engaged in twice weekly home-based progressive RT. At the end of the study, UC was given an online exercise program.

Results: Among 181 randomized patients (mean age, 55.2 [SD, 12.8] years, 95 [52.5%] were men), there were no differences in the mean RDI among those in RT (79% [SD, 19%]) and those in UC (82% [SD, 19%]); (mean difference -0.04 [95% confidence interval (CI), -0.09 to 0.02]). Assignment to RT did not significantly reduce the number of moderate/severe symptoms per week across follow-up (relative rate: 0.94 [95% CI, 0.72-1.22]). Additionally, time since randomization did not significantly modify the effect of RT on the overall number of symptoms (p = .06).

Conclusions: Among patients with colon cancer, these results do not support home-based RT as an adjunct to chemotherapy specifically to improve planned treatment intensity.

Keywords: colon cancer; exercise; randomized trial; relative dose intensity.

Figure 1.. Consort diagram

Ineligibility reasons (not mutually exclusive; do not add up to total above): Received treatment at non-study site location=121; Language barrier=100; Physical limitation=71; Other medical treatment or condition=57; Unable to recruit in protocol timeframe=44; Not new cancer, metastatic disease, or other cancer=42; Other reasons=42; Rectal cancer=37; No MD approval=35; Current resistance training=15; Unsafe to exercise=12; Not 6 mths FOLFOX (pre-amendment at DFCI)=11; Stopped chemotherapy=1; Enrolled in clinical trial=1; Cognitive impairment =1

Figure 2.. RDI by intervention arm

Models are adjusted for stage, sex, chemotherapy regimen and duration, and clinical site

Figure 3.. RDI by intervention arm and a priori determined and exploratory subgroups

Models are adjusted for stage, sex, chemotherapy regimen and duration, and clinical site

Figure 4.. The effect of resistance training (RT) vs usual care (UC) on the number of self-reported moderate/severe symptoms per week; a.) the average effect across time, and b.) each week since randomization

a.) The number of moderate/severe symptoms was modeled as a quadratic function of time since randomization, assigned intervention group, and the characteristics used in the randomization procedure; b.) adds a statistical interaction between intervention group and time since randomization. The expected count (and 95% CI) for those assigned to UC (blue) and RT (red) was estimated at a.) week 12 and b.) each time point PRO-CTCAE questionnaires were distributed based on this model for our referent group (recruited from Kaiser, stage 3, female, on FOLFOX, and on a 6-month regimen). The number of symptoms per week in the RT group relative to the UC group (and 95% CI) was estimated in a.) our model without the interaction between time and RT, and b.) our model with this interaction, reporting the p-value for the statistical interaction between intervention group and our function of time since randomization. The bottom charts the number of participants contributing questionnaire data at a.) any time point, and b.) at each time point among the UC and RT groups.