Medline ® Abstracts for References 111,115,124-126
of 'Fluoropyrimidine-associated cardiotoxicity: Incidence, clinical manifestations, mechanisms, and management'
Final results of Australasian Gastrointestinal Trials Group ARCTIC study: an audit of raltitrexed for patients with cardiac toxicity induced by fluoropyrimidines.
Ransom D, Wilson K, Fournier M, Simes RJ, Gebski V, Yip D, Tebbutt N, Karapetis CS, Ferry D, Gordon S, Price TJ
Ann Oncol. 2014 Jan;25(1):117-21. Epub 2013 Dec 2.
BACKGROUND: Cardiac toxicity an uncommon but serious side-effect of some fluoropyrimides. Cardiac toxicity from raltitrexed is rarely reported. With this background, we initiated this study to investigate the incidence of cardiac events in patients who had switched to raltitrexed following cardiac toxicity from fluoropyrimidines (5-fluorouracil or capecitabine).
PATIENTS AND METHODS: Pharmacy records were used to identify patients receiving raltitrexed from January 2004 till March 2012. Medical records were then reviewed to confirm the use of raltitrexed after cardiac toxicity from 5-fluorouracil or capecitabine. The primary end point was the rate of further cardiac events after commencing raltitrexed.
RESULTS: Forty-two patients were identified and the majority had colorectal cancer. Prior regimens included 5-fluorouracil±leucovorin, capecitabine alone, FOLFOX, FOLFIRI, epirubicin/cisplatin/5-fluorouracil, and capecitabine/oxaliplatin. Seven patients (17%) had bolus 5-fluorouracil regimens, 26 patients (62%) had infusion 5-fluorouracil regimens, and 9 patients (21%) had capecitabine alone or in combination. Angina was the most common cardiac toxicity from 5-fluorouracil or capecitabine and usually occurred in the first or the second cycle. Four patients after their first cardiac event continued with the same 5-fluorouracil or capecitabine regimen with the addition of nitrates and calcium antagonists but still had further cardiac events. After changing to raltitrexed, either as a single agent or a continuing combination regimen, no patients experienced further cardiac toxicity.
CONCLUSION: Raltitrexed is associated with no significant cardiac toxicity in patients who have experienced prior cardiac toxicity from 5-fluorouracil or capecitabine. Raltitrexed, alone or in combination with oxaliplatin or irinotecan, provides a safe option in terms of cardiac toxicity for such patients.
Oncology Department, St John of God and Royal Perth Hospital, Perth.
Raltitrexed (Tomudex): an alternative drug for patients with colorectal cancer and 5-fluorouracil associated cardiotoxicity.
Köhne CH, Thuss-Patience P, Friedrich M, Daniel PT, Kretzschmar A, Benter T, Bauer B, Dietz R, Dörken B
Br J Cancer. 1998 Mar;77(6):973-7.
Two patients with proven 5-fluorouracil (5-FU)-associated cardiotoxicity were treated with the specific thymidylate synthase inhibitor raltitrexed safely, without evidence of cardiotoxicity. Raltitrexed might be an alternative for patients with advanced colorectal cancer and 5-FU-associated cardiotoxicity. 5-FU cardiotoxicity is not due to the antineoplastic mechanisms via thymidilate synthase.
Department of Haematology/Oncology and Tumor Immunology Robert-Rössle-Klinik, Virchow-Klinikum, Medizinische Fakultät Charite der Humboldt-Universität zu Berlin, Germany.
Efficacy and safety of raltitrexed combinations with uracil- tegafur or mitomycin C as salvage treatment in advanced colorectal cancer patients: a multicenter study of Anatolian Society of Medical Oncology (ASMO).
Bozkurt O, Karaca H, Ciltas A, Kaplan MA, Benekli M, Sevinc A, Demirci U, Eren T, Kodaz H, Isikdogan A, Ozkan M, Buyukberber S
Asian Pac J Cancer Prev. 2014;15(4):1845-9.
BACKGROUND: There is no standard treatment for patients with colorectal cancer (CRC) progressing after irinotecan and oxaliplatin treatment. Here we aimed to retrospectively evaluate the efficacy and tolerability of raltitrexed in combination with oral 5-fluoropyrimidine (uracil tegafur-UFT) or mitomycin C as salvage therapy in mCRC patients.
MATERIALS AND METHODS: A total of 62 patients who had received raltitrexed combined with UFT or mitomycin C were identified between December 2008 and June 2013. They were given raltitrexed 2.6 mg/m2 (max 5 mg) i.v. on day 1 in combination with either oral UFT 500 mg/day on days 1-14 every 3 weeks (group A) or mitomycin C 6 mg/m2 i.v. on day every 3 weeks (group B).
RESULTS: Forty-two patients (67.7%) were in group A and 20 (32.2%) in group B. In 15 patients (24%) grade 3/4 toxicity was observed, resulting in dose reduction, and in 13 patients (20.9%) dose delay was necessary. The median progression free survival (PFS) was 3 months (95%CI 2.65-3.34) and median overall survival (OS) was 6 months (95%CI 2.09-9.90) in the whole group. Median PFS was 3 months (95%CI 2.60-3.39) in group A vs 3 months (95%CI 1.64-4.35) in group B (p=0.90). Median OS was 6 months (95%CI 2.47-9.53) in group A vs 12 months (95%CI 2.83-21.1) in group B (p=0.46).
CONCLUSIONS: The combination of raltitrexed with UFT or mitomycin C seem to be a salvage therapy option due to safety profile and moderate clinical activity in heavily-pretreated mCRC patients.
Department of Medical Oncology, Faculty of Medicine, Erciyes University, Kayseri, Turkey E-mail : firstname.lastname@example.org.
Use of raltitrexed as an alternative to 5-fluorouracil and capecitabine in cancer patients with cardiac history.
Kelly C, Bhuva N, Harrison M, Buckley A, Saunders M
Eur J Cancer. 2013 Jul;49(10):2303-10. Epub 2013 Apr 10.
AIM: Fluoropyrimidines are the backbone of the majority of approved chemotherapy regimens for colorectal cancer (CRC). However, there are reports of fluoropyrimidine treatments being associated with cardiotoxicity which have led to permanent cardiovascular damage and even death. Raltitrexed is indicated for palliative treatment of advanced CRC where 5-fluorouracil (5-FU) is not tolerated or inappropriate. A systematic review was undertaken to determine the incidence of cardiotoxicity associated with 5-FU, capecitabine and raltitrexed.
METHODS: An electronic search of PubMed was undertaken to identify articles relating to cardiotoxicity associated with 5-FU, capecitabine or raltitrexed, published between January 1991 and August 2011. Additionally, a retrospective review of cardiotoxicity associated with raltitrexed at our treatment centres was conducted.
RESULTS: Twenty studies were examined. The overall incidence of cardiotoxicity associated with 5-FU/capecitabine varied between 0.55% and 19% (mean: 5.0%, median: 3.85%). No published data were identified reporting cardiotoxicity associated with raltitrexed. A retrospective review at our treatment centres revealed that the incidence was 4.5% amongst high-risk patients treated with raltitrexed (n=111) for advanced gastrointestinal cancer with a significant cardiac history and/or previous cardiotoxicity with 5-FU or capecitabine.
CONCLUSION: The incidence of cardiotoxicity associated with raltitrexed in patients with advanced CRC treated is favourable in a highly skewed, at-risk patient population, all of whom had documented cardiotoxicity with other fluoropyrimidines or were unable to tolerate capecitabine due to cardiac history. Raltitrexed is therefore a suitable option for patients with fluoropyrimidine-induced cardiotoxicity or significant cardiovascular risk factors.
Christie Hospital, Wilmslow Road, Withington, Manchester M20 4BX, UK.
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