Efficacy and Cardiotoxic Safety Profile of Raltitrexed in Fluoropyrimidines-Pretreated or High-Risk Cardiac Patients With GI Malignancies: Large Single-Center Experience.
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Date
2019-03-01Author
Khan, K
Rane, JK
Cunningham, D
Rao, S
Watkins, D
Starling, N
Kalaitzaki, E
Forster, M
Braconi, C
Valeri, N
Gerlinger, M
Chau, I
Type
Journal Article
Metadata
Show full item recordAbstract
BACKGROUND: Gastrointestinal (GI) cancer patients may not be considered for therapy with fluoropyrimidines (FPs) because of previous cardiovascular (CV) toxicity or preexisting risk factors; such patients may benefit from raltitrexed-based therapy. PATIENTS AND METHODS: Patient, tumor, and treatment characteristics, as well as clinical outcomes of all consecutively treated patients with raltitrexed at the Royal Marsden Hospital between October 1998 and July 2011 were examined. GI cancer patients who developed CV toxicity as a result of FPs and those with significant CV risk factors receiving raltitrexed were included in this analysis. RESULTS: A total of 247 patients (155 and 92 with CV FP-related CV toxicities and significant CV risk factors, respectively) treated with raltitrexed alone or in combination were examined after a median follow-up of 47.1 months. CV toxicity profiles of patients receiving capecitabine (n = 110) and 5-fluorouracil (n = 45) were largely similar. Of raltitrexed-treated patients, 13 (5%) experienced CV toxicities and 1 (< 0.1%) died as a result of myocardial infarction. The median progression-free survival (PFS) and overall survival (OS) were 36.0 months (95% confidence interval [CI], 26.5-48.6) and 44.3 months (95% CI, 33.1-56.8), respectively. The 5-year survival for early stage GI malignancies (n = 140) was 62.0% (95% CI, 50.1-71.9). Median PFS and OS were not reached in this group (interquartile range = 38.4 months to NR); median PFS and OS for advanced GI malignancies (n = 107) were 18.8 (95% CI, 11.9-25.7) and 23.7 months (95% CI, 17.0-26.9), respectively. CONCLUSION: A raltitrexed-based regimen is well-tolerated therapy with comparable efficacy to FPs in patients with GI malignancies with significant CV toxicities or risk factors.
Collections
Subject
Humans
Gastrointestinal Neoplasms
Cardiovascular Diseases
Fluorouracil
Thiophenes
Quinazolines
Antineoplastic Combined Chemotherapy Protocols
Prognosis
Survival Rate
Retrospective Studies
Follow-Up Studies
Safety
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Male
Cardiotoxicity
Capecitabine
Research team
Signal Transduction & Molecular Pharmacology
Gastrointestinal Cancers Clinical Trials
Medicine (RMH Smith Cunningham)
Gastrointestinal Cancer Biology and Genomics
Translational Oncogenomics
Language
eng
Date accepted
2018-09-25
License start date
2019-03
Citation
Clinical colorectal cancer, 2019, 18 (1), pp. 64 - 71.e1
Publisher
CIG MEDIA GROUP, LP