Medline ® Abstracts for References 126,134,135
of 'Fluoropyrimidine-associated cardiotoxicity: Incidence, clinical manifestations, mechanisms, and management'
A randomized phase II study to compare oxaliplatin plus 5-fluorouracil and leucovorin (FOLFOX4) versus oxaliplatin plus raltitrexed (TOMOX) as first-line chemotherapy for advanced colorectal cancer.
Gravalos C, Salut A, García-Girón C, García-Carbonero R, León AI, Sevilla I, Maurel J, Esteban B, García-Rico E, Murias A, Cortés-Funes H
Clin Transl Oncol. 2012 Aug;14(8):606-12. Epub 2012 Jul 19.
INTRODUCTION: The aim of this study was to compare TOMOX versus FOLFOX4 as first-line treatment of advanced colorectal cancer (CRC).
MATERIALS AND METHODS: 191 chemotherapy-naïve patients were randomized to receive TOMOX or FOLFOX4. Patients were evaluated every 3 months and chemotherapy was continued until disease progression or unacceptable toxicity. Overall response rate was the primary endpoint.
RESULTS: 183 patients were included in the intent-to-treat analysis (92 TOMOX and 91 FOLFOX4). Overall response rate was 45.6 and 36.3 % (p = 0.003) for TOMOX and FOLFOX4, respectively. No statistically significant differences were observed in overall survival (15.6 and 17.2 months; p = 0.475); progression-free survival (7.7 and 8.7 months; p = 0.292), and response duration (6.4 and 7.6 months; p = 0.372) for TOMOX and FOLFOX4, respectively. Grades 3 and 4 neutropenia (p < 0.0001) and leukopenia (p = 0.028) were more common with the FOLFOX4 regimen, while hepatic disorders and asthenia were higher in TOMOX group (p = ns). There were two treatment-related deaths in the FOLFOX4 arm and one in the TOMOX arm. Quality of life analysis based on the SF-36 revealed differences between the two regimens for physical and mental composite scores after 6 weeks, and for body pain and emotional role functioning after 6 and 12 weeks; all of these favored the FOLFOX4 arm (p ≤ 0.05).
CONCLUSIONS: TOMOX and FOLFOX4 seem to have similar efficacy and are well tolerated in the first-line treatment for advanced CRC with different profiles of toxicity. The convenient TOMOX regimen may offer an alternative to fluoropyrimidine-based regimens.
Medical Oncology Department, University Hospital 12 de Octubre, Madrid, Spain. email@example.com
["Iatrogenic acute coronary syndrome"--59 year old patient with adenocarcinoma of ascending colon and stenocardia while receiving adjuvant chemotherapy with 5-fluorouracil].
Gundling F, Fuchs M, Nowak L, Antoni D, Hoffmann E, Schepp W
Z Gastroenterol. 2006 Sep;44(9):975-9.
Fluorouracil-associated cardiotoxic adverse events represent a relevant but underestimated problem in 5-fluorouracil treatment. After right hemicolectomy for adenocarcinoma of the rightsided colonic flexure a 59-year old patient was referred to our hospital for adjuvant chemotherapy according to MOSAIC-protocol with oxaliplatin and 5-fluorouracil. The patient's history was unremarkable for any cardiopulmonary disease and for any cardiovascular risk factors. 24 hours after completing the first cycle the patient was readmitted to our emergency department because of thoracic pain combined with significantly elevated cardiac enzymes and ischaemic changes in ECG. Coronary angiography was performed revealing no coronary artheriosclerosis. Clinical symptoms and pathological ischaemic serum parameters returned to normal range within 12 hours. Diagnosis of 5-FU-induced acute coronary syndrome could be made. Because of the high rate of recurring cardiotoxicity the patient's chemotherapy was modified to an alternative regimen containing raltitrexed instead of 5-fluorouracil. Immediate diagnosis of 5-FU-induced cardiotoxicity and differentiation from preexisting coronary heart disease is still a major problem in daily oncological practice.
II. Medizinische Abteilung für Gastroenterologie, Hepatologie und Gastroenterologische Onkologie, Städtisches Klinikum München GmbH, Klinikum Bogenhausen. Felix.Gundling@gmx.de
Adjuvant therapy with raltitrexed in patients with colorectal cancer intolerant of 5-fluorouracil: British Columbia Cancer Agency experience.
Wilson KS, Fitzgerald CA, Barnett JB, Gill S, Khoo KE
Cancer Invest. 2007;25(8):711.
BACKGROUND: Severe 5-FU toxicity in adjuvant therapy of colorectal cancer may require change of therapy. We retrospectively explored the safety and efficacy of adjuvant raltitrexed in patients intolerant of 5-FU.
METHODS: Over a 5 year period, patients who received 5-FU and subsequent raltitrexed therapy were identified.
RESULTS: There were 44 patients, (39 stage III). Median number of prior 5-FU cycles was 2. Three year relapse free and overall survival proportions for stage III patients were 70.8% and 83.6%, respectively.
CONCLUSIONS: Raltitrexed adjuvant therapy can be given safely and effectively in patients where further 5-FU is contraindicated.
Gastro-Intestinal Tumor Group, British Columbia Cancer Agency, Vancouver Island Centre, Victoria, British Columbia. KWilson@bccancer.bc.ca