P-0258patient profile and tolerability of raltitrexed in monotherapy and in combination with oxaliplatin as advanced colorrectal teatment. ralto study

Background: Fluoropyrimidines (FP) are the backbone of the majority chemotherapy regimens for advanced colorectal cancer (aCRC) although for some patients may be unsuitable (FP intolerance, DPD deficiency, prior FP unacceptable toxicity, history of ischemic heart disease, etc.). For these patients, treatment with Raltitrexed (R), a direct thymidylate synthase inhibitor, both in monotherapy and in combination with oxaliplatin (TOMOX), could be an effective alternative. Methods: We collected data between 2010 and 2012 from patients treated in 15 Spanish Hospitals. The primary endpoint of this observational retrospective study was to assess the tolerability of R or TOMOX as aCRC treatment in normal clinical practice. Secondary endpoints included the reason for choosing R or TOMOX as aCRC treatment, patient and disease characteristics and previous treatment and toxicity. Results: In this analysis it was included data from 144 patients treated with R (n = 72) and TOMOX (n = 72), 64% male, ECOG PS 0/1/2 in 18%/62%/19% and median age 68 years old (51% ≥70 years old). The mean time since diagnosis in the R group was 2.7 years and 1.8 years in the TOMOX group. The diagnosis was advanced colon cancer in 65% of patients and advanced rectal cancer in 35%. The mean number of metastatic sites was 1.78. While TOMOX was uniformly used first, second and third or subsequent treatment lines (37%, 28% and 35%), R was mainly used as third- or subsequent treatment line (64%). The mean number of cycles was 5 (1-15). Similar efficacy and safety to other treatments was the main reason to choose R (19%) followed by convenience of administration (18%) and pre-existing cardiovascular disease (17%). The main reason for discontinuation was disease progression. The creatinine clearance (CrCl) was only calculated in 20% of the cycles. Cycle 1 had the highest number of CrCl determinations (37.5%) but 21 patients were treated with higher dose of R than recommended by their CrCl value. The most common grade 3-4 toxicities were neutropenia (8%), anaemia (5%), nausea (2%), vomiting (1%), diarrhoea (7%) and hepatic toxicity (4%). There were 2 toxic deaths (1.4%). Conclusion: Raltitrexed in monotherapy and in combination with oxaliplatin, used in normal clinical practice, could be an effective and safe alternative for patients in which FP are unsuitable. Despite good tolerance to raltitrexed, it is essential to assess creatinine clearance before each treatment cycle.