levoleucovorin and Myocardial-Ischemia

Fluorouracil (FU) is a cornerstone of colorectal cancer treatment; however, it has clinical and subclinical influence on the heart. This study aimed to clarify the pathophysiology, risk factors, and long-term effects of FU cardiotoxicity.. The study prospectively accrued colorectal cancer patients (n=106) completely resected and adjuvantly treated with FU and oxaliplatin according to the FOLFOX4 regimen (infusional FU, folinic acid, and oxaliplatin). Serial measurements were made of systolic and diastolic features of the left ventricle by radionuclide ventriculography, plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), lactic acid, and ECG before chemotherapy, immediately after a treatment infusion, and at follow-up 2 weeks after cessation of the intended 12 treatment courses and were further evaluated by multivariate regression analysis that included cardiovascular history and its risk factors.. In the entire cohort, NT-proBNP significantly increased from baseline 14.5±3.2 pmol/L (mean±standard error) to 28.3±5.3 pmol/L during FU therapy (P<.001). Nine patients (8.5%) with cardiotoxicity had significantly higher NT-proBNP of 55.3±40.8 pmol/L compared with 25.4±4.1 pmol/L in those without (P<.001). In multivariate analysis, the FU-induced rise of NT-proBNP was significantly higher in females (P<.001). Plasma lactic acid significantly increased from baseline (1.3±0.1 mmol/L to 1.8±0.1 mmol/L) during FU therapy (P<.001). Left ventricular ejection fraction at baseline of 0.66±0.01 remained unchanged at 0.65±0.01 during FU therapy and 0.66±0.01 at follow-up (P=.4).. FU therapy generally induces myocardial neuroendocrine changes with increasing plasma NT-proBNP and lactic acid but without long-term dysfunction of the left ventricle. The usability of NT-proBNP as a predictive marker for FU cardiotoxicity remains to be clarified.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Colorectal Neoplasms; Female; Fluorouracil; Humans; Lactic Acid; Leucovorin; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Organoplatinum Compounds; Prospective Studies; Risk Factors; Ventricular Dysfunction, Left

The aim of this study was to evaluate the effects of a combination of folinic acid, 5-fluorouracil (5FU) and irinotecan (FOLFIRI 1) administered every 2 weeks in a population of elderly subjects with advanced colorectal cancer.. Patients with metastatic colorectal cancer included in this study were aged at least 70 years, with a performance status of 0/1, without geriatric syndrome and without previous palliative chemotherapy. They received irinotecan [180 mg/m(2) intravenous (iv) infusion over 90 min] followed by folinic acid (400 mg/m(2) iv over 2 h), then 5FU (400 mg/m(2) iv bolus) and 5FU (2,400 mg/m(2) continuous iv infusion for 46 h) every 2 weeks.. Forty eligible patients were included. The median age was 77.3 years (range 70-84.7). The objective response rate was 40% and the stabilisation rate was 45%. Median progression-free survival was 8 months, overall survival was 17.2 months and cancer-related specific survival was 20.2 months. In total, 300 cycles of chemotherapy were administered with a median number of eight cycles per patient (range 1-18). Tolerance was good; grade 3/4 toxicities included diarrhoea (15%), asthenia (15%), nausea/vomiting (7.5%) and neutropenia (7.5%). One toxic death was observed due to grade 4 diarrhoea.. The FOLFIRI 1 regimen is a valid therapeutic option for elderly patients in good clinical condition.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Combined Modality Therapy; Diarrhea; Disease-Free Survival; Fluorouracil; Hematologic Diseases; Humans; Leucovorin; Myocardial Ischemia; Organoplatinum Compounds; Oxaliplatin; Palliative Care; Patient Compliance; Prospective Studies; Quality of Life; Radiotherapy, Adjuvant; Survival Analysis

This study aimed to elucidate the influence of 5-fluorouracil (5-FU)-based therapy on the vascular endothelium and its association with 5-FU-induced heart ischemia.. The study prospectively accrued patients (n = 106) having completely resected colorectal cancer and receiving adjuvant treatment with 5-FU, folinic acid, and oxaliplatin. The levels of plasma von Willebrand factor (vWf), urine albumin-to-creatinine ratio (UACR), coagulation factor II + VII + X, and fibrin D-dimer were serially assessed before, during, and after chemotherapy.. The vWf level increased from median (range) 1.43 kU/l (0.48 to >3) to 2.64 kU/l (0.23 to >3) (P = 0.001), the UACR increased from 1.1 ± 0.2 mg/mmol (mean ± SE) to 2.1 ± 0.3 mg/mmol (P = 0.001), the coagulation factor II + VII + X activity decreased from 1.00 ± 0.02 to 0.94 ± 0.02 U/l (P = 0.001), and the fibrin D-dimer level increased from 1.1 ± 0.2 to 2.1 ± 0.3 kU/l (P = 0.001) at baseline and during chemotherapy, respectively. The changes in the levels of vWf (P = 0.3), UACR (P = 0.8), coagulation factor II + VII + X (P = 0.8), and fibrin D-dimer (P = 0.6) in nine (8.5%) patients having clinical signs of cardiotoxicity were not significantly different from that of the patients not having cardiotoxicity. The 5-FU-induced rise in plasma biomarkers was not significantly related to the cardiovascular morbidity or its risk factors (P = 0.9).. 5-FU therapy induces global reversible endothelial injury leading to a procoagulant state. The ensuing endothelial dysfunction may be of significance to the pathogenesis of 5-FU-induced clinically overt cardiotoxicity. Cardiovascular disease is not significant for the vulnerability of the endothelium to 5-FU-based chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Chemotherapy, Adjuvant; Colorectal Neoplasms; Combined Modality Therapy; Endothelium, Vascular; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Myocardial Ischemia; Organoplatinum Compounds; Prospective Studies; Risk Factors; von Willebrand Factor

Endostar® (Rh-endostatin injection) is a new recombinant human endostatin developed by Shandong Simcere-Medgenn Bio-Pharmaceutical Co., Ltd in China. This study was performed to evaluate the efficacy and safety of Endostar plus leucovorin calcium/ 5-fluorouracil/oxaliplatin (FOLFOX4) in treating patients with advanced colorectal cancer.. Thirty-six patients with advanced colorectal cancer were retrospectively assigned to one of two treatment groups: FOLFOX4 (control) or FOLFOX4 plus Endostar (Endostar) according to patient accreditation. The observational end points were overall response rate, overall survival, progression-free survival and toxicity.. The response rate and progression-free survival of Endostar were significantly better than those of control group (P <0.05), but significance was not observed for median survival. In addition, gastrointestinal side effects and incidence of leucopenia were not lower than in the control group (P<0.05).. The addition of Endostar to FOLFOX4 resulted in a higher objective response rate and longer time to disease progression. Hypertension and cardiac ischemia were the principal safety concerns, but were manageable. Endostar deserves to be further investigated by randomized controlled clinical trails.

Topics: Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Disease-Free Survival; Drug Administration Schedule; Endostatins; Female; Fluorouracil; Humans; Hypertension; Leucovorin; Male; Middle Aged; Myocardial Ischemia; Organoplatinum Compounds; Recombinant Proteins