Oral capecitabine as an alternative to i.v. 5-fluorouracil-based adjuvant therapy for colon cancer: safety results of a randomized, phase III trial

Scheithauer, Werner; McKendrick, J; Begbie, Steven; Borner, Markus; Burns, W. Ivon; Burris, Howard A.; Cassidy, Jim; Jodrell, Duncan I.; Koralewski, P.; Levine, Edward; Marschner, Norbert; Maroun, J.; García‐Alfonso, Pilar; Tujakowski, Jerzy; Hazel, G. Van; Wong, Alfred; Załuski, J.; Twelves, Chris

doi:10.1093/annonc/mdg500

Cited by 247 publications

(133 citation statements)

References 17 publications

Supporting

Mentioning

117

Contrasting

Unclassified

Order By: Relevance

“…Gastrointestinal side effects, such as diarrhoea, nausea and vomiting, which were also anticipated with the combination, occurred less frequently than usually seen with standard dose capecitabine single-agent therapy (Scheithauer et al, 2003). These side effects were readily managed with appropriate medical interventions, for example, loperamide and rehydration for diarrhoea and 5-HT 3 receptor antagonists and dexamethasone for nausea and emesis.…”

Section: Discussionmentioning

confidence: 96%

Capecitabine plus docetaxel every 3 weeks in first- and second-line metastatic oesophageal cancer: final results of a phase II trial

et al. 2005

View full text Add to dashboard Cite

Capecitabine and docetaxel have single-agent activity in upper gastrointestinal tumours, and have together demonstrated preclinical synergy and a survival benefit in breast cancer, and high response rates in first-line metastatic gastric cancer. This trial assessed the efficacy, safety and feasibility of capecitabine in combination with docetaxel in patients with metastatic oesophageal cancer. In all, 24 patients with advanced disease (17 squamous cell carcinoma and seven adenocarcinoma) received oral capecitabine (1000 mg m À2 twice daily on days 1 -14) plus intravenous docetaxel (75 mg m À2 on day 1) every 3 weeks as first-(n ¼ 16) or second-line (n ¼ 8) therapy. Patients received a median of four cycles of treatment (range, 0 -6). The median follow-up is 16.5 months (range, 7.9 -21.4 months). Intent-to-treat efficacy analysis showed an overall response rate of 46%. Of the 11 responders (one complete and 10 partial), nine of 16 (56%) received first-line and two of eight (25%) received second-line therapy. The median time to progression was 6.1 months (95% confidence interval (CI), 4.5 -7.7 months). The meian survival was 15.8 months (95% CI, 7.8 -23.9 months). Severe adverse events (grade 3/4) reported were: neutropenia (42%, including febrile neutropenia 8%), hand-foot syndrome (29%), diarrhoea (13%), sensory neuropathy (13%), anaemia (8%) and fatigue (8%). Capecitabine plus docetaxel has a manageable adverse event profile and very promising activity in metastatic oesophageal cancer, at least comparable to other doublet regimens. Therefore, the combination merits further investigation in this setting.

show abstract

Section: Discussionmentioning

confidence: 96%

Capecitabine plus docetaxel every 3 weeks in first- and second-line metastatic oesophageal cancer: final results of a phase II trial

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Its efficacy as first-line treatment in metastatic colorectal cancers (MCRC) has been shown in randomised trials (Twelves, 2002). Its safety as an alternative to intravenous 5FU-based adjuvant therapy for colon cancer has been addressed (Scheithauer et al, 2003). Capecitabine achieves longterm inhibition of the target enzyme thymidylate synthase, and in this way mimics the continuous intravenous infusion of 5FU.…”

mentioning

confidence: 99%

A phase I trial of preoperative radiotherapy and capecitabine for locally advanced, potentially resectable rectal cancer

et al. 2004

View full text Add to dashboard Cite

The purpose of the study was to determine the maximum-tolerated dose (MTD) of oral capecitabine, combined with concurrent, standard preoperative pelvic radiotherapy, when given twice daily, from Monday to Friday throughout the course of radiotherapy, for locally advanced potentially resectable rectal cancer. Maximum-tolerated dose was defined as the total (given in two equally divided doses) oral dose of capecitabine that caused treatment-related grade 3 or 4 toxicity in one-third or more of the patients treated. Radiotherapy involved 50.4 Gy given in 28 fractions in 5 weeks and 3 days. Eligible patients had a newly diagnosed clinical stage T3 -4 N0 -2 M0 rectal adenocarcinoma located within 12 cm of the anal verge suitable for curative resection. Surgery was performed 4 -6 weeks from completion of preoperative chemoradiotherapy. In all, 28 patients were enrolled in the study at predefined dose levels: 850 mg m À2 day À1 (n ¼ 3), 1000 mg m À2 day À1 (n ¼ 6), 1250 mg m À2 day À1 (n ¼ 3), 1650 mg m À2 day À1 (n ¼ 3), 1800 mg m À2 day À1 (n ¼ 8) and 2000 mg m À2 day À1 (n ¼ 5). The mean age was 62.3 years (range: 33 -80 years). Five patients were female and 23 male. The median distance of tumour from the anal verge was 6 cm (range: 1 -11 cm). Endorectal ultrasound was performed in 93% of patients. A total of 26 patients (93%) had T3 disease and two patients had resectable T4 disease. Dose-limiting toxicity (DLT) developed in one patient at dose level 1000 mg m À2 day À1 (RTOG grade 3 cystitis). Two of the five patients at dose level 2000 mg m À2 day À1 had a total of three DLT (grade 3 perineal skin reaction, grade 3 diarrhoea and grade 3 dehydration). Dose escalation of capecitabine was ceased at 2000 mg m À2 day À1 after reaching MTD. None of the eight patients at dose level 1800 mg m À2 day À1 developed DLT. All except one patient underwent surgery. A total of 15 patients had the clinical T stage reduced by at least one stage in pathologic specimens. Five patients (19%) achieved a pathologic complete response. We conclude that the MTD of capecitabine was reached at a dose level of 2000 mg m À2 day À1 , given as 1000 mg m À2 twice daily, from Monday to Friday throughout the course of preoperative pelvic irradiation of 50.4 Gy. For patients with resectable rectal cancer receiving concurrent, full dose radiotherapy, the recommended dose of capecitabine for further study is 1800 mg m À2 day À1 when given in this schedule.

show abstract

“…In patients with metastatic colorectal cancer, capecitabine is an established firstline treatment and has now replaced intravenous (IV) 5-FU. 1 The toxic effect of IV 5-FU on the coronary endothelium and myocardium is rare but it can be lethal with potential myocardial infarction, ventricular arrhythmias and sudden death. 2 In a recent Swedish analysis the incidence of reported 5-FU cardiotoxicity is around 4.3%, but is higher when renal function is impaired.…”

Section: Discussionmentioning

confidence: 99%

Acute chest pain in a patient treated with capecitabine

Camaro¹,

Danse²,

Bosker³

2009

NHJL

View full text Add to dashboard Cite

A 61-year-old male with a history of metastatic colorectal cancer was referred to our hospital for primary coronary intervention because of acute ST-elevation myocardial infarction. Coronary angiography, however, revealed no significant stenoses. When asked, the patient revealed that capecitabine (Xeloda ® ) was started by his oncologist one day before admission. It is known that this oral 5-FU analogue drug, used in metastatic colorectal cancer, can cause coronary artery spasms. A 61-year-old male was admitted to a referring hospital because of acute chest pain. Three years ago he had suffered an acute coronary syndrome. Coronary angiography (CAG) showed focal coronary sclerosis in the right coronary artery, but no obstructive lesions and the patient was treated conservatively with aspirin, metoprolol, isosorbide-5-mononitrate and rosuvastatin. Furthermore, he had colon cancer with metastases in the liver and the lungs.After dinner the patient experienced 30 minutes of retrosternal chest pain without radiation. Because the chest pain was not relieved by sublingual nitroglycerin he contacted his general practitioner who sent him to hospital for observation. At the referring hospital he had no symptoms. The electrocardiogram (ECG) at admittance showed sinus rhythm with early repolarisation (figure 1). Four hours after admission, while waiting for the second troponin, there was recurrence of heavy retrosternal chest discomfort with radiation to the left arm. A new ECG was taken immediately and revealed sinus rhythm with ST-segment elevation in the inferolateral leads and peaked T-waves ( figure 2). An ST-elevation myocardial infarction was diagnosed and he was sent to our hospital for primary coronary intervention. Immediate treatment with 600 mg clopidogrel, 5000 units heparin and 160 mg aspirin was initiated and he was sent directly to our catheterisation laboratory. At presentation to the catheterisation laboratory he was free of symptoms. CAG revealed diffuse coronary sclerosis, but no significant stenosis in the coronary arteries with TIMI 3 flow in all vessels. In comparison with his CAG performed three years ago, no changes were seen. He was admitted to the coronary care unit. His blood pressure was 134/70 mmHg and the pulse 77 beats/min. There was no fever. No abnormalities were discovered on physical examination. The cardiac enzymes and the inflammation parameters were not elevated. His renal function was normal. Transthoracic echocardiography showed normal left and right ventricular function and no pericardial effusion. Two hours later, the severe chest discomfort returned with ST-segment elevation similar to the ECG at the referring hospital and nitroglycerin IV was started. Because of the intermittent character of his complaints with concomitant ST-segment changes, coronary artery vasospasms were now suspected as the cause of the symptoms. When asked, the patient revealed that capecitabine (Xeloda ® ) 1500 mg twice a day had been started just one day earlier. Capecitabine can indeed cause coronary arte...

show abstract

Oral capecitabine as an alternative to i.v. 5-fluorouracil-based adjuvant therapy for colon cancer: safety results of a randomized, phase III trial

Abstract: Based on its improved safety profile, capecitabine has the potential to replace 5-FU/LV as standard adjuvant treatment for patients with colon cancer. Efficacy results are expected to be available in Keywords: Adjuvant treatment, capecitabine, chemotherapy, colorectal cancer

Cited by 247 publications

References 17 publications

Capecitabine plus docetaxel every 3 weeks in first- and second-line metastatic oesophageal cancer: final results of a phase II trial

Capecitabine plus docetaxel every 3 weeks in first- and second-line metastatic oesophageal cancer: final results of a phase II trial

A phase I trial of preoperative radiotherapy and capecitabine for locally advanced, potentially resectable rectal cancer

Acute chest pain in a patient treated with capecitabine

Contact Info

Product

Resources

About