Abstract
ObjectivePatients with metastatic colorectal cancer (mCRC) had oncological benefits with irinotecan dose escalation of FOLFIRI regimen combined with bevacizumab according to UGT1A1 genotypes in our previous study. In the current study, we performed a quality of life (QOL) outcome evaluation and cost-utility analysis of different irinotecan dose regimens in patients with mCRC.Materials and MethodsWith inverse probability-of-treatment weighting (IPTW) matching on all covariates, 75 patients with dose escalation of irinotecan (study group) and 121 patients with the recommended dose of irinotecan (control group) were recruited between October 2015 and December 2019. The QOL outcome measures were Functional Assessment of Cancer Therapy-Colorectal, Beck Anxiety Inventory, Beck Depression Inventory, and SF-36; cost-utility outcome measures were medical direct costs, quality-adjusted life-years (QALYs), and incremental cost-utility ratios (ICURs).ResultsAll mCRC patients exhibited a significant decrease in both emotional wellbeing and depression from pretherapeutic period to posttherapeutic 6th month (P < 0.05); however, from the posttherapeutic 1st year to the 2nd year, improvement in most QOL measures was significantly better in the study group than in the control group (P < 0.05). Over a 2-year time period, the study group had higher total medical direct costs than the control group (US$ 54,742 ± 14,013 vs. US$ 54,608 ± 9,673) and higher average QALYs gained (1.88 vs. 1.65), with an ICUR of US$ 583 per QALY gained.ConclusionFor patients with mCRC, irinotecan dose escalation appeared cost-effective with considerable QOL improvements during the study period. Further randomized, multi-institutional controlled trials are warranted to corroborate these results.
Highlights
The recommended irinotecan dose in the FOLFIRI regimen is 180 mg/m2 based on a dose-finding study [2, 4, 10]
According to the above criteria, metastatic colorectal cancer (mCRC) patients were divided into two groups: 75 patients were categorized into the dose escalation group (>180 mg/m2, study group) and 121 patients into the recommended dose group (180 mg/m2, control group)
Total medical direct costs Incremental costs Utility Pretherapeutic Posttherapeutic 6th month Posttherapeutic 1st year Posttherapeutic 2nd year Quality adjusted life years (QALYs) Incremental QALYs Incremental cost utility ratio (ICUR). In both groups of patients with mCRC, physiological functions and emotional wellbeing significantly worsened at posttherapeutic 6th month compared with the pretherapeutic status
Summary
With the recent advances in pharmacogenomic era, patients undergo genetic testing to determine their genotype before treatment, based on which a suitable medication or dosage is administered [1–3]. For metastatic colorectal cancer (mCRC) patients, the standard chemotherapy regimens are 5-fluorouracil (5-FU), leucovorin, and oxaliplatin (FOLFOX); oxaliplatin with capecitabine (CAPOX); or 5-FU, leucovorin, and irinotecan (FOLFIRI). Our previous multicenter, randomized, controlled, open-label trial study revealed that exceeding the recommended irinotecan dose is safe and effective when a regimen of FOLFIRI plus bevacizumab is administered in mCRC patients with UGT1A1∗1/ ∗1 and UGT1A1∗1/∗28 genotypes. Pretherapeutic UGT1A1 genotyping–guided dose adjustment achieved better outcomes compared to the standard regimen. This intention-totreat (ITT) analysis demonstrated the benefits of escalating doses of irinotecan under UGT1A1 genotyping. Other previous studies have suggested that higher doses of irinotecan in the first-line or later-line setting in mCRC can confer favorable clinical outcomes [4–7]
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