scholarly journals Early Clinical Experience with Trifluridine/Tipiracil for Refractory Metastatic Colorectal Cancer: The ROS Study

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4514
Author(s):  
Pilar García-Alfonso ◽  
Andrés Muñoz ◽  
Jerónimo Jiménez-Castro ◽  
Paula Jiménez-Fonseca ◽  
Carles Pericay ◽  
...  

Trifluridine/tipiracil is currently approved for metastatic colorectal cancer (mCRC) refractory to available therapies. However, there is no consensus on factors that predict treatment outcomes in daily practice. We assessed the early clinical experience with trifluridine/tipiracil in Spain and potential survival markers. This was a retrospective cohort study of mCRC patients who participated in the trifluridine/tipiracil early clinical experience programme in Spain. The primary outcome was overall survival (OS). Associations between OS and patient characteristics were assessed using multivariate Cox regression analyses. A total of 379 patients were included in the study. Trifluridine/tipiracil was administered for a median of 3.0 cycles and discontinued mainly due to disease progression (79.2%). The median OS was 7.9 months, with a 12-month OS rate of 30.5%. Cox analyses revealed that the following variables independently enhanced OS: ≤2 metastatic sites, no liver metastasis, alkaline phosphatase < 300 IU, trifluridine/tipiracil dose reductions, and neutrophil/lymphocyte ratio < 5. Grade ≥ 3 toxicities were reported in 141 (37.2%) patients, including mainly afebrile neutropaenia (23.2%), anaemia (12.1%), and thrombocytopaenia (5.3%). This study supports the real-life efficacy and safety of trifluridine/tipiracil for refractory mCRC and identifies tumour burden, liver metastasis, alkaline phosphatase, dose reductions, and neutrophil/lymphocyte ratio as survival markers.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15556-e15556
Author(s):  
Pilar Garcia-Alfonso ◽  
Andres J. Muñoz Martín ◽  
Jeronimo Jimenez-Castro ◽  
Paula Jiménez-Fonseca ◽  
Carles Pericay ◽  
...  

e15556 Background: Trifluridine/tipiracil is currently approved for metastatic colorectal cancer (mCRC) refractory to available therapies. However, there is no consensus on factors that predict treatment outcomes in daily practice. We assessed the early clinical experience with trifluridine/tipiracil in Spain and potential survival markers. Methods: This was a retrospective cohort study of mCRC patients who participated in the trifluridine/tipiracil early clinical experience program in Spain. The primary outcome was overall survival (OS). Associations between OS and patient characteristics were assessed using multivariate Cox regression analyses. Results: A total of 379 patients were included in the study. Trifluridine/tipiracil was administered for a median of 3.0 cycles and discontinued mainly due to disease progression (79.2%). The median OS was 7.9 months, with a 12-month OS rate of 30.5%. Cox analyses revealed that the following variables independently favoured OS: ≤2 metastases, no liver metastasis, alkaline phosphatase < 300 IU, trifluridine/tipiracil dose reductions, and neutrophil/lymphocyte ratio < 5. Grade ≥3 toxicities were reported in 141 (37.2%) patients, including mainly afebrile neutropenia (23.2%), anaemia (12.1%), and thrombocytopenia (5.3%). Conclusions: This study supports the real-life efficacy and safety of trifluridine/tipiracil for refractory mCRC and identifies tumour burden, liver metastasis, alkaline phosphatase, dose reductions, and neutrophil/lymphocyte ratio as survival markers.


2017 ◽  
Vol 33 (3) ◽  
pp. 185-189 ◽  
Author(s):  
Ersin Borazan ◽  
Ahmet Abdulhalik Balik ◽  
Zehra Bozdag ◽  
Muhammed Kasim Arik ◽  
Alper Aytekin ◽  
...  

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3598-3598 ◽  
Author(s):  
Zhi-Yu Chen ◽  
Christopher Hanyoung Lieu ◽  
Zhi-Qin Jiang ◽  
Cathy Eng ◽  
Jean-Nicolas Vauthey ◽  
...  

3598 Background: High blood neutrophil-to-lymphocyte ratio (NLR) has been previously identified as a poor prognostic marker in patients with metastatic colorectal cancer (mCRC). However, the underlying pathophysiology associated with this marker is not well defined. We validated this biomarker and investigated the relationship between circulating cytokines and high NLR. Methods: NLRs were calculated retrospectively from the ratio of peripheral blood absolute neutrophil and lymphocyte counts, and segregated based on previously determined cutoff of ≤5 and >5. Four cohorts with a total of 805 CRC pts were evaluated to confirm the prognostic clinical significance of NLR. Plasma cytokine levels were evaluated in exploratory (n=39) and validation cohorts (n=166) of previously untreated mCRC patients using multiplex-bead assays, and correlated with NLR. Results: High NLR is present in 20% of CRC patients and is associated with poor prognosis, independent of known prognostic factors (Table). Expression of 6 cytokines (IL-6, IL-8, IL-2Ra, HGF, M-CSF and VEGF) correlated with NLR>5 in both the exploratory and validation cohort. In the validation cohort, an additional 14 cytokines correlated with NLR>5, including high EREG,AREG, and TGF-α, and low TRAIL. By hierarchial clustering, these 20 cytokines fall into 3 overlapping major clusters: angiogenic cytokines, inflammatory cytokines, and epidermal growth factor ligands. In the validation cohort, pts with a composite cytokine score below the median have longer survival than patients with high scores (40.0 mo vs 20.0 mo, HR = 2.24; 95% CI=1.47–3.41; P<0.001). Conclusions: High peripheral blood neutrophil/lymphocyte ratio (NLR) is associated with poor outcomes independent of other known prognostic features. NLR correlates with discrete sets of cytokines which may reflect important biological features in poor prognosis mCRC. [Table: see text]


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 660-660 ◽  
Author(s):  
Suee Lee ◽  
Hyuk-Chan Kwon ◽  
Sung-Hyun Kim ◽  
Sung Yong Oh ◽  
Ji Hyun Lee ◽  
...  

660 Background: Oxaliplatin- and irinotecan-based combination chemotherapy with infusional 5-FU and leucovorin are currently the standard therapies for metastatic colorectal cancer. The objectives of this study were to evaluate the efficacy of capecitabine monotherapy as third line therapy for metastatic colorectal cancer after failure of chemotherapy containing oxaliplatin and irinotecan, and to determine whether the neutrophil-lymphocyte ratio (NLR), or the platelet-lymphocyte ratio (PLR) are significant prognostic marker in metastatic colorectal cancer. Methods: We analyzed 60 patients with metastatic colorectal cancer who received capecitabine monotherapy after the failure of FOLFOX and FOLFIRI. Capecitabine was administered at 1250mg/m2 twice daily for 2 weeks, every 3 weeks. The NLR and PLR were calculated from complete blood counts in baseline laboratory test before the first cycle chemotherapy. Results: The overall response rate was 6.7% and stable disease was 41.7%. The disease control rate was 48.3%. The median progression-free survival (PFS) was 2.8 months (95% CI, 1.5-4.1 months) and the median overall survival (OS) was 9.7 months (95% CI, 7.6-11.7 months). The most frequent adverse event was hand-foot syndrome (all-grade 26.6%; grade3 5%). The response of capecitabine, NLR, and PLR were observed as good prognostic markers of OS in univariate analysis (p<0.001, 0.004, and 0.002, respectively). The response of capecitabine and PLR were independent prognostic marker in multivariate analysis (Hazard ratio 2.757, 95% CI 1.357-5.599, p=0.005 and hazard ratio 2.091, 95% CI 1.231-3.552, p=0.006, respectively). Conclusions: The capecitabine monotherapy showed a moderate disease control and a tolerable toxicity profile as third line treatment for metastatic colorectal cancer. The response of capecitabine and PLR may be simple and useful prognostic index for metastatic colorectal cancer.


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