This prospective study included older patients scheduled for adjuvant chemotherapy after complete resection of colon cancer. The patients were enrolled consecutively if they met the following inclusion criteria: provided written informed consent, were aged over 65 years, were diagnosed with adenocarcinoma stage II high-risk (T4, poorly differentiated/undifferentiated tumor, perineural invasion, lymphatic/vascular invasion, less than 12 lymph nodes examined, or localized perforation) or stage III disease, had undergone complete resection, had Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0–2 (0, fully active; 1, restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; 2, ambulatory and capable of all self-care but unable to carry out any work activities, up and about for more than 50% of waking hours), and received adjuvant chemotherapy.

Three regimens of adjuvant chemotherapy were included: capecitabine monotherapy (1,250 mg/m² twice daily for 14 days every 3 weeks, 8 cycles), FOLFOX (oxaliplatin at 85 mg/m² intravenously on day 1, and 5-FU 400 mg/m² bolus intravenously on day 1 and 1,200 mg/m² continuous intravenously on days 1 and 2 every 2 weeks, 12 cycles), and CAPOX (oxaliplatin at 130 mg/m² intravenously on day 1 and capecitabine at 1,000 mg/m² twice daily for 14 days, 8 cycles). The term “relative dose intensity” is used to define the proportion of actual dose delivered divided by the standard calculated dose during each regimen. It is expressed as a percentage. The completion of chemotherapy was defined as the patient having received the standard cycles for each regimen for 6 months following surgery. Otherwise, it was considered to be an interruption in treatment. The adjuvant chemotherapy was determined by the physician’s preference based on the patient’s condition. Dose reduction was at the discretion of the physician at the initiation of chemotherapy. We performed a stratification for the following factors: sex (male or female), body mass index (BMI; underweight, < 18.5 kg/m²; normal, 18.5–22.9 kg/m²; overweight-obese, ≥ 23 kg/m²), comorbidity (yes or no), hemoglobin level (< 10 or ≥ 10 g/dL), CrCl (estimated glomerular filtration rate < 60 or ≥ 60 mL/min/1.73 m²), ECOG PS (0–1 or 2), and stage (II or III).

Hematologic and non-hematologic toxicities were noted at each cycle and at the end of treatment based on medical records. These data were analyzed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. This study was approved by the Institutional Review Board of Chonnam National University Hwasun Hospital (IRB No. CNUHH-2016-140) and written informed consent was obtained from all patients.

Functional status was evaluated by well-trained assistants within 1 week prior to beginning chemotherapy using the ECOG PS, ADL, and IADL. ADLs comprise the following seven items: dressing, washing face and hair, bathing, eating, transferring, toileting, and continence. IADLs comprise the following 10 items: decorating, housework, preparing meals, laundry, going out for short distances, using transportation, shopping, handling money, using the telephone, and taking medicine. The ADL and IADL were based on Katz’s ADL [18] and Lawton’s IADL [19], which reflect the Korean language and culture [21]. We defined the impairment of ADL/IADL as those patients who showed a loss of self-sufficiency in one or more of the domains of ADL or IADL [22].

The characteristics of the population were summarized as frequencies and percentages for categorical variables and as medians and ranges for continuous variables. Comparisons between groups were performed using the chi-square or Fisher’s exact tests for categorical variables and the Mann-Whitney or t tests for continuous variables.

Logistic regression analysis was performed to obtain the significant predictors for the interruption of adjuvant chemotherapy. All tests were two-sided, and p < 0.05 was considered statistically significant. Statistical analyses were performed using IBM SPSS Statistics for Windows version 21.0 (IBM Corp., Armonk, NY, USA).

From June 2017 through November 2019, 96 patients were prospectively enrolled. Among them, seven patients were excluded, three for metastatic lesions after surgery, two for rectal cancer requiring radiation therapy, one for refusing chemotherapy, and one diagnosed with double primary cancer. Therefore, 89 patients were analyzed. Their baseline characteristics are described in Table 1. The median age was 72 years (range, 65 to 83). Regarding the age distribution of this study, the age range exists for multiple categories. We analyzed the age range by dividing it into two groups based on median age (72 years). Compared to patients younger than 72 years (n = 49), patients over 72 years (n = 40) showed no difference in characteristics except for ECOG PS.

ADL/IADL analysis classified 54 patients (61%) in the non-impairment of ADL/IADL category and 35 patients (39%) in the impairment of ADL/IADL category. There were no differences in clinical characteristics between the non-impairment and impairment categories except for ECOG PS (p = 0.014).

Analysis of the patterns of adjuvant chemotherapy according to the physician’s choice showed that oxaliplatin-based chemotherapy was administered significantly more often to patients who were younger (≤ 72 years) or had non-impairment of ADL/IADL. This was compared to patients who were older > 72 years (p < 0.001; Fig. 1A) or had impairment of ADL/IADL (p = 0.013; Fig. 1B). In total, 19 patients (21%) received capecitabine, 43 patients (48%) received FOLFOX, and 27 patients (30%) received CAPOX. Among them, 75 patients (84%) completed the planned treatment cycle. In detail, 11 patients (58%) were administered capecitabine, 39 patients (91%) were administered FOLFOX, and 25 patients (93%) were administered CAPOX and completed their planned cycles. The dosage was reduced in 81 patients (91%) during the first cycle, and the median dosage strength in the first cycle was 80%. There was no significant difference in the dosage strength for each regimen according to age and the ADL/IADL group, except for capecitabine monotherapy in the ADL/IADL categories. The completion rates of adjuvant chemotherapy did not differ significantly between age or categories by ADL/IADL classification, for each type of adjuvant chemotherapy regimen (Table 2).

Analysis of the clinical characteristics related to chemotherapy completion showed significant associations with age, the chemotherapy regimen, and BMI in univariate analysis and BMI and ADL/IADL in multivariate analysis (Table 3).

In addition to patient baseline characteristics, toxicity following chemotherapy was also a critical issue related to chemotherapy interruption. Therefore, we analyzed this association with the incidence of toxicity according to age, ADL/IADL, and chemotherapy interruption (Table 4). There was no significant difference in hematologic toxicity. The most common treatment-related hematologic toxicity was neutropenia. One case of febrile neutropenia with severe infection was reported. The patient recovered with antibiotics and in-hospital therapy. However, the patient discontinued chemotherapy because of poor PS. The most common non-hematologic toxicities of any grade were chemotherapy induced nausea and vomiting (CINV), chemotherapy induced peripheral neuropathy (CIPN), hand-foot syndrome (HFS), diarrhea, and fatigue (43%, 43%, 22%, 20%, and 24% respectively). CINV developed more frequently in patients in the non-impairment of ADL/IADL category (53.5%, p = 0.020) and this result would be related with the more use of oxaliplatin based chemotherapy in patients with non-impairment of ADL/IADL than in patients with impairment of ADL/IADL. Likewise, CIPN developed more frequently in patients in the younger-age group (53.1%, p = 0.052) and in the non-impairment of ADL/IADL category (53.7%, p = 0.020). According to age, the cumulative dose of oxaliplatin in younger age group was higher in FOLFOX (younger 756.66 mg/m² > older 712.21 mg/m²) and CAPOX (younger 808.37 mg/m² > older 673.40 mg/m²) than in older patients. As with age, the cumulative dose of oxaliplatin in the non-impairment of ADL/IADL category was higher in the FOLFOX (non-impair 743.31 mg/m² > impair 723.99 mg/m²) and CAPOX (non-impair 818.66 mg/m² > impair 699.56 mg/m²) than in the impairment category. For these reasons, our results may contribute to an explanation of the risks of developing CIPN due to the cumulative dose of oxaliplatin. Other non-hematologic toxicities were reported in 12 cases, followed by eight cases of oxaliplatin induced hypersensitivity, two cases of infection, one case of hyponatremia, and one case of hepatitis. Interestingly, the incidence of fatigue was significantly higher in patients with impairment of ADL/IADL, regardless of age. Among the toxicities, HFS more than grade G3 and chemotherapy induced fatigue were significantly associated with chemotherapy interruption in multivariate analysis (Table 5). Except for HFS, which is directly related to chemotherapy such as capecitabine, chemotherapy induced fatigue was the only significant factor to predict chemotherapy completion. Among the baseline clinical parameters, low BMI, and impairment of ADL/IADL were associated with chemotherapy induced fatigue in univariate and multivariate analyses (Table 6).

Therefore, we divided patients into four groups based on age (≤ 72 or > 72 years) and functional status by ADL/IADL (non-impairment or impairment) to predict the completion rate of adjuvant chemotherapy according to each regimen. As shown in Fig. 2A, patients with a younger age (≤ 72 years) and non-impairment of ADL/IADL more often received CAPOX, while patients with an older age (> 72 years) and impairment of ADL/IADL more often received capecitabine monotherapy (p < 0.001). In addition, younger patients (≤ 72 years) and/or those with non-impairment of ADL/IADL were significantly more likely to complete adjuvant chemotherapy than were older patients (> 72 years) and those with impairment of ADL/IADL (p = 0.038; Fig. 2B), regardless of the chemotherapy regimen.