1539P - Liver toxicity in colorectal cancer patients treated with first line FOLFIRI-containing regimen: A single institution experience

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anticancer Agents
Complications/Toxicities of Treatment
Colon and Rectal Cancer
Biological Therapy
Presenter Marco Imperatori
Citation Annals of Oncology (2014) 25 (suppl_4): iv517-iv541. 10.1093/annonc/mdu356
Authors M. Imperatori1, B. Vincenzi2, A. Picardi2, U. Vespasiani Gentilucci2, V. Fausti2, M. Spalato Ceruso2, D. Santini2, G. Tonini2
  • 1Medical Oncology, university campus bio-medico, 00128 - Roma/IT
  • 2Medical Oncology, Campus Bio-Medico di Roma, 00128 - Roma/IT



This study aims to evaluate the mechanisms of liver toxicity in the specific group of mCRC patients treated with FOLFIRI-based regimens, calculating the R ratio and the AST/ALT ratio and retrospectively comparing patients treated with SAMe supplementation with patients who did not receive the supplementation.


156 mCRC patients receiving a FOLFIRI backbone-based regimen were included in this analysis. Liver enzymes levels (AST, ALT, total bilirubin, gamma-glutamyltransferase, alkaline phosphatise) were assessed before starting the treatment (basal value) and then before every therapy course. R ratio and the AST/ALT ratio was calculated in patients developing liver toxicity. 46 out of 156 patients received an oral supplementation of SAMe (400 mg twice a day).


AST, ALT and alkaline phosphatase (AP) has shown a significant modification after the beginning of first line treatment. Specifically, both AST level (123.87 vs 41.05U/l; P <0.001), ALT level (94.48 vs 39.80 U/l; P=0.004) and AP (289.0 vs 172.44 U/l; P=0.02) were found to be significantly increased during the first three months of treatment. In the entire CRC population the calculated R ratio was 3.96 (3.25-4.51). In all the three regimens the calculated R ratio was between 2 and 5 (FOLFIRI=4.10; BEVA-FOLFIRI=3.76; CETUXIMAB-FOLFIRI=4.35), without any statistical differences between regimens, supporting a mixed pattern of hepatic injury. Globally, 25 (16.02%) patients out of 156 needed coursed delays and 12 (7.69%) patients received a dose reduction, and only three patients (1.92%) stopped the first line therapy due to liver toxicity. In details, Grade 3-4 hypertransaminase, was less frequently observed in the small group of patients treated with SAMe (2.17% vs 16.37%; P=0.029). In addition, patients treated with SAMe supplementation required in a lower number chemotherapy course delays (4.35% vs 20.90%, P=0.020).


For the first time in literature, pattern of chemotherapy-induced liver injury has been indirectly defined upon the evaluation of R-Ratio, revealing the mixed pattern of liver damage. SAMe supplementation prevent hepatotoxicity in a specific group of mCRC patients treated with FOLFIRI-containing regimens reducing Grade 3-4 hypertransaminase (2.17% vs 16.37%; P=0.029) and treatment delays (4.35% vs 20.90%, P=0.020).


All authors have declared no conflicts of interest.