Irinotecan dose reduction in metastatic colorectal cancer patients with homozygous polymorphism: a single-center case series.

OBJECTIVE

The polymorphism reduces enzymatic activity, which may increase the risk of severe toxicity in patients who receive standard-dose irinotecan, such as severe neutropenia and diarrhea. This real-world study assessed the optimal irinotecan dose in terms of efficacy and toxicity in metastatic colorectal cancer (mCRC) patients homozygous for the polymorphism and receiving FOLFIRI plus bevacizumab or cetuximab as first-line therapy.

METHODS

We analyzed toxicity and treatment outcomes in seven mCRC patients who were homozygous for and received FOLFIRI plus bevacizumab or cetuximab, with an initial irinotecan dose of 120 mg/m.

RESULTS

Six of the seven patients tolerated 120 mg/m irinotecan without requiring dose reductions in subsequent cycles. The overall response and disease control rates were 43.0% (3/7) and 71.4% (5/7), respectively. The median progression-free survival and overall survival were 11.0 and 33.0 months, respectively. Only one severe adverse event, grade III neutropenia (2.5%), was observed.

CONCLUSIONS

mCRC patients homozygous for the allele can tolerate irinotecan at an initial dose of 120 mg/m with favorable oncological outcomes and toxicity profiles. Further prospective studies are warranted to optimize irinotecan-based chemotherapy in these patients.