Liver toxicity in colorectal cancer patients treated with first-line FOLFIRI-containing regimen: a single institution experience

Abstract

Background: Chemotherapy-induced toxic liver injury is a relevant issue in the clinical management of patients affected with metastatic colorectal cancer (mCRC). This retrospective study evaluated patterns of liver toxicity in patients treated with FOLinic acid, Fluorouracil, IRInotecan (FOLFIRI)-based regimens. Methods: One hundred and fifty-six mCRC patients treated at the University Campus Bio-Medico between January 2003 and January 2013 were included in this retrospective analysis. All patients received a FOLFIRI backbone-based chemotherapy. Basal liver enzymes levels were assessed before starting the treatment and before every therapy course. R ratio and the aspartate aminotransferase/alanine aminotransferase ratio were calculated. Results: Ninety-one patients were male versus 55 female, and the median age of the population was 62 years (range: 38–83). Most patients had liver involvement at the beginning of first-line regimen (101 patients, 64.74%) and 59 patients had received a previous 5-FU based therapy in the adjuvant setting (37.82%). Aspartate aminotransferase level (167.87 vs 41.05 U/l; p < 0.001), Alanine aminotransferase level (94.48 vs 39.80 U/l; p = 0.004) and alkaline phosphatase (289.0 vs 172.44 U/l; p = 0.02) were significantly increased during the first 3 months of treatment. In the entire population, the calculated R ratio was 3.96 (95% CI: 3.25–4.51). In all three regimens, the calculated R ratio was between 2 and 5, without any statistical differences. Conclusions: FOLFIRI-based hepatotoxicity has been indirectly defined as a mixed pattern injury in all three regimens evaluated.

Keywords:

• AST\ALT ratio
• hepatotoxicity
• irinotecan
• R ratio
• retrospective study

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• This study aimed to indirectly evaluate the patterns of liver toxicity in a specific group of mCRC patients treated with FOLFIRI-based regimens, calculating the R ratio and aspartate aminotransferase (AST)/alanine aminotransferase(ALT) ratio and highlighted the mixed pattern of liver damage during FOLinic acid, Fluorouracil, IRInotecan (FOLFIRI)-based regimens.

• The hepatic injury was significantly associated with chemotherapy administration regardless of the combined targeted therapy.

• S-adenosylmethionine supplementation has been proven to reduce hepatotoxicity in oxaliplatin-based chemotherapy. More studies evaluating SAMe supplementation in FOLFIRI-based chemotherapy would be of interest.

• Prospective studies evaluating R-ratio modification during treatment with other specific chemotherapeutic agents are needed.