Fluoropyrimidine-induced cardiotoxicity

Depetris, Ilaria; Marino, Donatella; Bonzano, Alessandro; Cagnazzo, Celeste; Filippi, Roberto; Aglietta, Massimo; Leone, Francesco

doi:10.1016/j.critrevonc.2018.02.002

Cited by 51 publications

(41 citation statements)

References 64 publications

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“…Familiarity with the literature highlighting the reversibility of trastuzumab-associated cardiotoxicity; use of biomarkers to predict cardiotoxicity in patients receiving cancer therapy; and increased comfort among cardiologists in managing cardiotoxicity, likely account for these changing results in our survey [28][29][30]. The second case described the most common manifestation of 5-FU cardiotoxicity: angina [31][32][33]. More oncologists decided to switch therapy to raltitrexed rather than rechallenge with 5-FU.…”

Section: Discussionmentioning

confidence: 89%

An international survey of healthcare providers’ knowledge of cardiac complications of cancer treatments

et al. 2019

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Background: Cardio-oncology is a young sub-specialty that addresses the needs of cancer patients at risk of, or who have experienced cancer therapy related cardiac dysfunction (CTRCD). This study assessed clinicians' understanding of cardio-oncology, opinions towards current practice, and approach to diagnosing and managing CTRCD. Methods: A 45-question survey was administered online via Survey Monkey and WeChat to health care providers (HCPs) comprising of cardiologists, oncologists, and others from September 2017 to March 2018. Implementation of the survey followed a modified Dillman's Total Design Method. Results: In total, 160 responses were collected from 22 countries; majority were from cardiologists (53.8%) and oncologists (32.5%). The remaining 13.7% identified themselves as "others," including general internists, cardiooncologists, pediatric oncologists, radiation oncologists, cardiac rehabilitation therapists, nurse practitioners, research students, and pharmacists. In the setting of metastatic cancer, there was a difference in risk tolerance for cardiotoxicity between subspecialties. In this case, more cardiologists (36.7%) accepted a 5-10% risk of cardiotoxicity compared to oncologists (20.0%). Majority of cardiologists felt that cardiotoxicity should be monitored, even in asymptomatic cancer patients (55.8%). Only 12% of oncologists selected this response. In contrast, 50.0% of oncologists reported that cardiologists should be involved only when patients develop cardiotoxicity. In comparison, 6.5% of cardiologists selected this response. Majority of cardiologists stated that cardio-oncology clinics would significantly improve cancer patients' prognosis (88.3%); only 45.8% of oncologists shared this opinion. Of all respondents, 66.9% stated they were familiar with a variety of international guidelines for managing cardiotoxicity. Of all oncologists, 65.3% indicated that they referred to these guidelines for clinical decision making. Conclusions: Despite the growth of cardio-oncology clinics, there are significant knowledge gaps regarding prevention and treatment strategies for CTRCD among health care providers. Knowledge translation from guidelines and collaboration between cardiologists and oncologists are needed to improve cardiovascular outcomes of cancer patients.

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Section: Discussionmentioning

confidence: 89%

An international survey of healthcare providers’ knowledge of cardiac complications of cancer treatments

et al. 2019

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“…The great burdens of CVD deaths were observed among patients who had colorectal, hematologic, and urinary tract cancers, but not for those who had other cancer types. In the absence of treatment data from this population‐based cancer registry, it is unclear whether cardiotoxicity caused by anticancer treatment played a role, but the literature has demonstrated connections between conventional anticancer drugs (eg, anthracyclines, cyclophosphamide, and fluoropyrimidines), novel targeted cancer therapies (eg, kinase inhibitors), and cardiac dysfunction, including heart failure, vascular thrombosis, and cardiac ischemia . Opportunities for better cardioprotective interventions might be considered for the oldest patients with cancer and for those who had a first diagnosis of colorectal, hematologic, and urinary tract cancer.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular and other competing causes of death among patients with cancer from 2006 to 2015: An Australian population‐based study

Otáhal

Marwick

et al. 2018

Cancer

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Background With improved cancer survivorship, cardiovascular disease (CVD) and other noncancer events compete with cancer as the underlying cause of death, but the risks of mortality in competing‐risk settings have not been well characterized. Methods The authors identified 21,637 individuals who had a first cancer registered between 2006 and 2013, with follow‐up to 2015, in the Australian population‐based Tasmanian Cancer Registry. The cumulative incidence of deaths from specific competing events was assessed in competing‐risk analyses. Standardized mortality ratios (SMRs) and absolute excess risks (AERs) for deaths from noncancer causes were calculated for comparison with the general population. Results Overall, 8844 deaths were observed, with 1946 (22%) from competing events. The cumulative incidence of deaths from CVD increased significantly with age at first cancer diagnosis and exceeded other competing events at age ≥65 years. The risk of death from CVD was more common than expected in the first year of follow‐up (SMR, 1.44 [95% confidence interval, 1.26‐1.64]; AER, 36.8 per 10,000 person‐years). The SMR and AER for CVD deaths varied by first cancer site, indicating increased risks after a first diagnosis of lung cancer, hematologic malignancy, and urinary tract cancer. For other noncancer events, the SMRs increased significantly for deaths from infectious disease and respiratory disease and were highest in the first year of follow‐up. Conclusions CVD was the leading cause of competing mortality among Tasmanian patients with cancer who were diagnosed from 2006 to 2013. The higher than expected occurrence of death from CVD and other noncancer events during the first year after a cancer diagnosis highlights the importance of early preventive interventions.

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“…As a result, it was reasonable to give a special attention to the hepatic function of patient before each cycle to prevent the severe hepatic toxicity from happening, especially for patients with heavy metastatic burden in liver. Moreover, in view of uoropyrimidines induced cardiotoxicity [23,24] and hand-foot syndrome (HFS) [25,26], the cardiotoxic safety pro le of raltitrexed in patients with CRC was fully con rmed in a series of studies [27][28][29], since neither cardiotoxic AEs nor HFS was observed in our study, suggesting raltitrexed seemed to have a better toxicity pro le compared to capecitabine or 5-FU, especially because of a lower incidence of HFS and cardiotoxicity. RIR might be an alternative to FOLFIRI and XELIRI for patients with mCRC who were not candidates for uoropyrimidine-based combination therapy.…”

Section: Discussionmentioning

confidence: 51%

Biweekly Raltitrexed in Combination with Irinotecan (RIR) as Second-Line Therapy for Patients with Metastatic Colorectal Cancer: A Non-Randomized, Open-Label Phase II Trial.

Cheng

Zhou

Chen

et al. 2020

Preprint

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Background Irinotecan-based doublet chemotherapy strategy was standard second-line backbone treatment for patients with oxaliplatin‑refractory metastatic colorectal cancer(mCRC). The aim of this study was to evaluate tolerability and efficacy of raltitrexed combined with irinotecan biweekly administered as the second-line therapy for mCRC patients.Methods The study was a single-center, non-randomized, open-label phase II trial. Patients with mCRC after failure with first-line treatment of oxaliplatin and fluoropyrimidine or its derivatives were enrolled. Irinotecan (180 mg/m2) and raltitrexed (2.5 mg/m2) were given intravenously on day 1. Cycles were repeated every 2 weeks. The primary endpoint was progression-free survival, and the secondary endpoints included overall response rate, disease control rate, overall survival and treatment related adverse events. Results Between December 2012 and October 2016, 35 patients were enrolled. 33 and 35 patients were assessed for response and safety, respectively. The overall response rate (ORR) was 8.6 %, and the disease control rate (DCR) was 71.4%. The median progression-free survival (PFS) was 4.5 months (95% CI 3.8–5.2). The median overall survival was 12.0 months (95% CI 8.5–15.5). Four patients received conversion therapy to no evidence of disease (NED), and 2 patients were still alive with beyond 24 months survival. The most common grade 3/4 hematological adverse events were leukopenia (8.6%), neutropenia (5.7%). The most common grade 3/4 nonhematological adverse events were anorexia (14.3%), vomiting (14.3%), nausea (11.4%) and fatigue (8.6%). Two patients discontinued the protocol treatment because of treatment-related gastrointestinal adverse events. No one died from treatment-related events. The incidence and severity of toxicity was irrelevant to UGT1A1 status.Conclusions The combination of irinotecan with raltitrexed is an active, convenient and acceptable toxic regimen for second-line treatment for mCRC patients, which needs further study as a chemotherapy backbone to be combined with targeted agents in mCRC.Trial registration No. ChiCTR-ONC-12002767. The study was registered with the Chinese Clinical Trial Registry at 29 Octorber 2012, http://www.chictr.org.cn/index.aspx.

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Fluoropyrimidine-induced cardiotoxicity

Cited by 51 publications

References 64 publications

An international survey of healthcare providers’ knowledge of cardiac complications of cancer treatments

An international survey of healthcare providers’ knowledge of cardiac complications of cancer treatments

Cardiovascular and other competing causes of death among patients with cancer from 2006 to 2015: An Australian population‐based study

Biweekly Raltitrexed in Combination with Irinotecan (RIR) as Second-Line Therapy for Patients with Metastatic Colorectal Cancer: A Non-Randomized, Open-Label Phase II Trial.

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