Comparison of adverse events during 5-fluorouracil versus 5-fluorouracil/oxaliplatin adjuvant chemotherapy for stage III colon cancer: a population-based analysis

Abstract

Background: In clinical trials, combined 5-fluorouracil (5FU) plus oxaliplatin improves the survival of patients who have resected, stage III colon cancer with manageable toxicity. However, the tolerability of this in the general population of patients with colon cancer is uncertain.

Methods: Adverse outcomes were compared in patients with stage III colon cancer who received either 5FU or 5FU/oxaliplatin within 120 days of undergoing resection versus a control group of patients with stage II colon cancer who did not receive chemotherapy in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database and in data from the New York State Cancer Registry linked to Medicare and Medicaid. Hospitalizations, emergency room (ER) visits, and outpatient adverse events (AEs) were measured in claims from 30 days to 9 months after patients underwent resection. Multiple logistic regression was used to calculate adjusted odds ratios of events by treatment. Propensity score matching was used to minimize selection bias.

Results: Adverse outcomes were more frequent for chemotherapy recipients. AE rates were higher in patients who received 5FU/oxaliplatin (81%) compared with patients who received 5FU alone (72%), in the SEER-Medicare data. The effect of oxaliplatin on AEs was greater in older patients: The odds ratio was 2.10 (95% confidence interval, 1.53-2.87) for patients aged ≥ 75 years versus 1.75 (95% confidence interval, 1.39-2.21) for patients aged <75 years. ER use was high in Medicaid patients (83% of those who received chemotherapy), but neither ER use nor hospitalization was increased by oxaliplatin. The 60-day mortality rate was 1% to 3% for patients who received 5FU alone and 1% to 2% for patients who received combined 5FU/oxaliplatin.

Conclusions: The incremental harms of adjuvant chemotherapy with 5FU/oxaliplatin versus 5FU alone were modest in patients with stage III colon cancer who were insured by Medicare and Medicaid. The additional harms in patients aged ≥ 75 years largely were restricted to outpatient events and did not extend to an increased rate of hospitalization or early death.

Figure 1

A: Stage III Cohort Assembly B: Stage II Cohort Assembly † Registry-claims files linked here. * Enrollment restrictions applied to the 12 months following diagnosis. HMO restriction applied to Medicare patients only.

Figure 1

A: Stage III Cohort Assembly B: Stage II Cohort Assembly † Registry-claims files linked here. * Enrollment restrictions applied to the 12 months following diagnosis. HMO restriction applied to Medicare patients only.

Figure 2

Adverse outcomes are illustrated according to postoperative treatment. Outcomes were measured during an 8-month window beginning 30 days after patients underwent surgical resection. (A) Outpatient adverse events are illustrated, including diarrhea, dehydration, nausea/vomiting, neutropenia, infections, deep venous thrombosis and pulmonary embolus, acute coronary syndromes, transient ischemic attack, stroke, and neuropathy. 5FU indicates 5-fluorouracil; SEER, Surveillance, Epidemiology, and End Results. (B) Emergency room (ER) visits are illustrated. (C) Hospitalizations are illustrated.

Figure 2

Adverse outcomes are illustrated according to postoperative treatment. Outcomes were measured during an 8-month window beginning 30 days after patients underwent surgical resection. (A) Outpatient adverse events are illustrated, including diarrhea, dehydration, nausea/vomiting, neutropenia, infections, deep venous thrombosis and pulmonary embolus, acute coronary syndromes, transient ischemic attack, stroke, and neuropathy. 5FU indicates 5-fluorouracil; SEER, Surveillance, Epidemiology, and End Results. (B) Emergency room (ER) visits are illustrated. (C) Hospitalizations are illustrated.

Figure 2

Adverse outcomes are illustrated according to postoperative treatment. Outcomes were measured during an 8-month window beginning 30 days after patients underwent surgical resection. (A) Outpatient adverse events are illustrated, including diarrhea, dehydration, nausea/vomiting, neutropenia, infections, deep venous thrombosis and pulmonary embolus, acute coronary syndromes, transient ischemic attack, stroke, and neuropathy. 5FU indicates 5-fluorouracil; SEER, Surveillance, Epidemiology, and End Results. (B) Emergency room (ER) visits are illustrated. (C) Hospitalizations are illustrated.

Figure 3

The duration of adjuvant chemotherapy is illustrated according to the propensity score (PS) in (A) PS-matched patients aged <75 years and (B) PS-matched patients aged ≥75 years. SEER indicates Surveillance, Epidemiology, and End Results; 5FU, 5-fluorouracil; Ox, oxaliplatin.

Figure 3

The duration of adjuvant chemotherapy is illustrated according to the propensity score (PS) in (A) PS-matched patients aged <75 years and (B) PS-matched patients aged ≥75 years. SEER indicates Surveillance, Epidemiology, and End Results; 5FU, 5-fluorouracil; Ox, oxaliplatin.