Abstract
The impact of cycle completion rates of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer in real-world practice is unknown. We assessed its impact, and that of treatment modification, on 3-year cancer-specific mortality. Four thousand one hundred and forty-seven patients with pathological stage III colon cancer undergoing major resection from 2014 to 2017 in the English National Health Service were included. Chemotherapy data came from linked national administrative datasets. Competing risk regression analysis for 3-year cancer-specific mortality was performed according to completion of <6, 6-11, or 12 5-fluoropyrimidine and oxaliplatin (FOLFOX) cycles, or <4, 4-7, or 8 capecitabine and oxaliplatin (CAPOX) cycles, adjusted for patient, tumour and hospital-level characteristics. Median age was 64 years. Thirty-two per cent of patients had at least one comorbidity. Forty-two per cent of patients had T4 disease, and 40% had N2 disease. Compared to completion of 12 FOLFOX cycles, cancer-specific mortality was higher in patients completing <6cycles [subdistribution hazard ratios (sHR) 2.17; 95% CI 1.56-3.03] or 6-11 cycles (sHR 1.40; 95% CI 1.09-1.78) (P < .001). Compared to completion of 8 CAPOX cycles, cancer-specific mortality was higher in patients completing <4cycles (sHR 2.02; 95% CI 1.53-2.67) or 4-7cycles (sHR 1.63; 95% CI 1.27-2.10) (P < .001). Dose reduction and early oxaliplatin discontinuation did not impact mortality in patients completing all cycles. Completion of all cycles of chemotherapy was associated with improved cancer-specific survival in real-world practice. Poor prognostic factors may have affected findings, however, patients completing <50% of cycles had poor outcomes. Clinicians may wish to facilitate completion with treatment modification in those able to tolerate it.
Highlights
| INTRODUCTIONAdjuvant chemotherapy after a planned curative surgical resection for stage III colon cancer is an established treatment.[1,2] many patients do not complete the planned duration of chemotherapy, even in clinical trials, and in real-world practice this proportion is even higher with non-completion rates reported as high as 45%.3,4 The impact of not completing adjuvant oxaliplatin-based chemotherapy on patient outcomes in real-world practice is unknown
Adjuvant chemotherapy after a planned curative surgical resection for stage III colon cancer is an established treatment.[1,2] many patients do not complete the planned duration of chemotherapy, even in clinical trials, and in real-world practice this proportion is even higher with non-completion rates reported as high as 45%.3,4 The impact of not completing adjuvant oxaliplatin-based chemotherapy on patient outcomes in real-world practice is unknown.5-fluoropyrimidine and oxaliplatin (FOLFOX) and capecitabine and oxaliplatin (CAPOX) have been shown in randomised controlled trial (RCT) to improve outcomes compared to fluoropyrimidines alone.[5,6,7] After publication of this data, standard practice involved 6 months of adjuvant chemotherapy (8 cycles of CAPOX or 12 cycles of FOLFOX)
The adjusted risk of 3-year cancer-specific death in patients with dose. This is the largest cohort study of real-world practice to date evaluating cancer-specific survival according to the cycle completion rates of oxaliplatin-based adjuvant chemotherapy in stage III colon cancer patients, and the first to assess the impact of treatment modification strategies
Summary
Adjuvant chemotherapy after a planned curative surgical resection for stage III colon cancer is an established treatment.[1,2] many patients do not complete the planned duration of chemotherapy, even in clinical trials, and in real-world practice this proportion is even higher with non-completion rates reported as high as 45%.3,4 The impact of not completing adjuvant oxaliplatin-based chemotherapy on patient outcomes in real-world practice is unknown. One study showed that 59% of stage II or III colon cancer patients in a real-world setting would not be eligible for RCT inclusion.[13] Population-based studies, using data such as electronic healthcare records, are needed to assess the effectiveness of actual durations of adjuvant chemotherapy on outcomes in diverse non-selected populations under routine clinical conditions to complement trial findings.[14,15,16,17,18]. Previous studies have not evaluated the survival impacts of treatment modifications (eg, dose reductions) which aim to reduce toxicity and support completion of the target duration of therapy In this national population-based study using linked administrative datasets, we assessed the impact of the cycle completion rate of oxaliplatin-based adjuvant chemotherapy on cancer-specific survival for stage III colon cancer patients treated in the English NHS, accounting for important confounders in the largest observational study to date. The effects of treatment modification on cancerspecific survival, namely dose reduction and early discontinuation of oxaliplatin, were analysed
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