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Quality of life and survival of metastatic colorectal cancer patients treated with trifluridine-tipiracil (QUALITAS)

24 maart 2022


The RECOURSE trial demonstrated a modest benefit in overall survival (OS) for trifluridine/tipiracil (FTD/TPI) versus placebo in pretreated metastatic colorectal cancer (mCRC) patients. Unfortunately, quality of life (QoL) was not assessed. We evaluated QoL and survival of patients treated with FTD/TPI in daily practice.


QUALITAS is a substudy of the Prospective Dutch CRC cohort (PLCRC). From 150 mCRC patients treated with FTD/TPI, QoL (EORTC QLQ-C30 and QLQ-CR29) was assessed monthly from study entry and linked to clinical data of the Netherlands Cancer Registry. Joint models were constructed combining mixed effects models with Cox PH models. Primary endpoint was difference in QoL over time (which was deemed clinically relevant if ≥10 points). Secondary endpoints were progression-free survival (PFS), time to treatment failure (TTF), and OS. We analyzed the association between QLQ-C30 Summary Score (QoL-SS) at FTD/TPI initiation (baseline) and survival.


There was no clinically relevant change in QoL-SS from baseline to 10 months post-baseline (i.e. the cut-off point after which 90% of patients had discontinued FTD/TPI treatment): -5.3 [95% CI -8.7;-1.5]. Patients who were treated with FTD/TPI for ≥3 months (n=85) reported 6.3 [1.6;11.1] points higher baseline QoL, compared to patients treated <3 months (n=65, ‘poor responders’). In the latter, time to a clinically relevant QoL deterioration was <2 months. Median PFS, TTF and OS were 2.9 [2.7;3.1], 3.1 [2.9;3.2] and 7.7 [6.6;8.8] months, respectively. Worse baseline QoL-SS was independently associated with shorter OS (HR 0.45 [0.32;0.63]), PFS (0.63 [0.48;0.83]), and TTF (0.64 [0.47;0.86]).


The maintenance of QoL during FTD/TPI treatment in daily practice supports its use. The QoL deterioration in ‘poor responders’ is likely due to disease progression. The strong association between worse baseline QoL and shorter survival suggests that clinicians should take QoL into account when determining prognosis and treatment strategy for individual patients.

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Long-Term Safety Data on S-1 Administered After Previous Intolerance to Capecitabine-Containing Systemic Treatment for Metastatic Colorectal Cancer

2 maart 2022


The oral fluoropyrimidine S-1 has shown comparable efficacy to capecitabine in Asian and some Western studies on metastatic colorectal cancer. S-1 is associated with a lower incidence of hand-foot syndrome (HFS) and cardiac toxicity. We assessed the long-term tolerability of S-1 in patients who discontinued capecitabine for reasons of HFS or cardiac toxicity.


Patients and Methods

Patients with metastatic colorectal cancer who switched from capecitabine to S-1, given as monotherapy or in combination with other agents, were identified in a Dutch prospective cohort study (2016-2021). The incidence and severity of HFS, cardiotoxicity and other toxicities were assessed.



Forty-seven patients were identified. The median duration of capecitabine treatment was 81 days (range 4-454). In 19 patients (40%) a dose reduction was applied prior to switch to S-1. Reasons for discontinuation of capecitabine were HFS in 36 (77%) patients, coronary artery vasospasms in 10 (21%) patients, and gastrointestinal toxicities in 1 patient (2%). The median number of S-1 cycles was 6 (range 1-36). The median time between last dose of capecitabine and first dose of S-1 was 11 days (range 1-49). After switch to S-1, all patients with prior HFS developed a lower grade or complete resolution of symptoms, and in all other patients symptoms did not recur. Other S-1-related adverse events were limited to grade 1-2. Six patients (13%) discontinued S-1 due to either known fluoropyrimidine-related or bevacizumab-related toxicities. Switch to S-1 did not appear to compromise treatment efficacy.



S-1 is a valid alternative to capecitabine in case HFS or cardiotoxicity occurs.

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Physical Activity Is Associated with Improved Overall Survival among Patients with Metastatic Colorectal Cancer

21 februari 2022

Regular physical activity (PA) is associated with improved overall survival (OS) in stage I–III colorectal cancer (CRC) patients. This association is less defined in patients with metastatic CRC (mCRC). We therefore conducted a study in mCRC patients participating in the Prospective Dutch Colorectal Cancer cohort. PA was assessed with the validated SQUASH questionnaire, filled-in within a maximum of 60 days after diagnosis of mCRC. PA was quantified by calculating Metabolic Equivalent Task (MET) hours per week. American College of Sports and Medicine (ACSM) PA guideline adherence, tertiles of moderate to vigorous PA (MVPA), and sport and leisure time MVPA (MVPA-SL) were assessed as well. Vital status was obtained from the municipal population registry. Cox proportional-hazards models were used to study the association between PA determinants and all-cause mortality adjusted for prognostic patient and treatment-related factors. In total, 293 mCRC patients (mean age 62.9 ± 10.6 years, 67% male) were included in the analysis. Compared to low levels, moderate and high levels of MET-hours were significantly associated with longer OS (fully adjusted hazard ratios: 0.491, (95% CI 0.299–0.807, p-value=0.005) and 0.485 (95% CI 0.303–0.778, p-value=0.003), respectively), as were high levels of MVPA (0.476 (95% CI 0.278–0.816, p-value=0.007)) and MVPA-SL (0.389 (95% CI 0.224–0.677, p-value<0.001)), and adherence to ACSM PA guidelines compared to non-adherence (0.629 (95% CI 0.412–0.961, p-value=0.032)). The present study provides evidence that higher PA levels at diagnosis of mCRC are associated with longer OS.

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