Oral Capecitabine Compared With Intravenous Fluorouracil Plus Leucovorin in Patients With Metastatic Colorectal Cancer: Results of a Large Phase III Study

Cutsem, Éric Van; Twelves, Chris; Cassidy, Jim; Allman, David; Bajetta, Emilio; Boyer, Michael; Bugat, R.; Findlay, M; Frings, S.; Jahn, Michaela K.; McKendrick, J; Osterwalder, B; Perez-Manga, G.; Rosso, Riccardo; Rougier, Philippe; Schmiegel, Wolff; Seitz, Jean‐François; Thompson, Paul; Vieitez, José María; Weitzel, Christof; Harper, Peter

doi:10.1200/jco.2001.19.21.4097

Cited by 941 publications

(499 citation statements)

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“…These trials demonstrated that capecitabine showed increasing efficacy in terms of response rate, equivalent time to progression and survival, and had a superior safety profile. 4,5,7 It is noteworthy that response rates were consistently higher for capecitabine than for 5-FU/LV in subgroups that included patients with liver metastasis (25% vs. 17%, respectively) and patients with lung metastasis (30% vs. 8%, respectively). 4 In our study, we found a strong anti-metastatic efficacy of capecitabine in the HT-29 cell rectal xenograft model wherein capecitabine showed low susceptibility in the xenograft itself.…”

Section: Discussionmentioning

confidence: 97%

“…4 -6 Randomized clinical trials that compared capecitabine with parenteral 5-FU/leucovorin against metastatic colorectal cancer demonstrated that capecitabine provides at least equivalence, a favorable benefit-risk ratio and greater patient preference making it an acceptable replacement for 5-FU/leucovorin. 4,5,7 Our interest focused on the possibility of capecitabine usage in the prevention of metastasis. Neoadjuvant or adjuvant chemotherapy to inhibit spontaneous metastasis or suppress occult micrometastasis may reduce the incidence of postoperative distant metastasis and improve survival.…”

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confidence: 99%

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Anti‐metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum

Ninomiya

Terada

Yoshizumi

et al. 2004

Intl Journal of Cancer

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Key words: capecitabine; lymph node metastasis; lung metastasis; thymidine phosphorylase; rectal xenograft modelGastrointestinal cancer is one of the most common internal malignancies and is one of the leading causes of cancer-related morbidity and mortality in the world. The primary definitive treatment modality is surgical excision. Adjuvant therapies subsequent to surgery have been studied extensively in recent years because of the high incidence of postoperative recurrences. More than 40 years after its development, 5-FU remains the chemotherapeutic mainstay for the management of patients with many types of cancer. In recent years, several new approaches to the treatment of cancer have undergone examination. These include the introduction of 2 novel cytotoxic compounds. Another strategy that has received attention has been the development of several oral forms of fluoropyrimidine, offering an alternative route of administration to intravenous 5-FU 1 . Capecitabine (N 4 -pentyloxycarbonyl-5Ј-deoxy-5-fluorocytidine) is a new fluoropyrimidine carbamate, which is designed to be activated to 5-FU by 3 sequential steps of enzyme reactions. 1 In humans, it is sequentially converted first to 5Ј-deoxy-5-fluorocytidine by carboxylesterase located in the liver, then to 5Ј-deoxy-5-fluorouridine by cytidine deaminase also with high activity in the liver and in various solid tumors and finally to 5-FU by thymidine phosphorylase (dThdPase) with high activity in many types of tumors. [1][2][3] This oral fluoropyrimidine has an advantage over parental therapy with 5-FU in its potential for affording patients greater convenience and comfort. 4 -6 Randomized clinical trials that compared capecitabine with parenteral 5-FU/leucovorin against metastatic colorectal cancer demonstrated that capecitabine provides at least equivalence, a favorable benefit-risk ratio and greater patient preference making it an acceptable replacement for 5-FU/leucovorin. 4,5,7 Our interest focused on the possibility of capecitabine usage in the prevention of metastasis. Neoadjuvant or adjuvant chemotherapy to inhibit spontaneous metastasis or suppress occult micrometastasis may reduce the incidence of postoperative distant metastasis and improve survival. To confirm this possibility, large randomized clinical trials should be needed. These clinical trials are expensive and time consuming. Animal experiments may take their place to examine the efficacy of new therapeutic modalities. Here, we develop an animal model of gastrointestinal cancer by the intrarectal injection of tumor cells, which resulted in the formation of local tumors with lymph node and lung metastasis consistent with the progression of gastrointestinal cancer in humans.In our study, we examined the efficacy of capecitabine for the inhibition of metastasis and its mechanism for doing so by using a mouse metastasis model. MATERIAL AND METHODS AnimalsMale BALB/c-nu/nu mice aged 5 weeks were obtained from Charles River Japan, Inc. (Kanagawa, Japan). After at least 1 week of observation, th...

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Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

Anti‐metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum

Ninomiya

Terada

Yoshizumi

et al. 2004

Intl Journal of Cancer

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“…Since the efficacy and favourable safety profile of capecitabine have been clearly demonstrated in recent large phase III studies comparing capecitabine with intravenous 5-FU plus leucovorin for metastatic colorectal cancer (Hoff et al, 2001;Van Cutsem et al, 2001), capecitabine has been widely used in the treatment of breast cancer, stomach cancer, and other solid tumours (Blum et al, 1999;Kim et al, 2002Kim et al, , 2003. Capecitabine also offers a number of potential advantages as a chemoradiosensitiser in concurrent chemoradiotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…In a preclinical study, capecitabine given orally resulted in consistently higher tissue-to-plasma 5-FU concentration ratios than 5-FU administered intravenously . In addition, capecitabine has also exhibited antitumour activity when given as a monotherapy or in combination with cisplatin in patients with various solid tumours as well as in advanced HNSCC (Blum et al, 1999;Van Cutsem et al, 2001;Kim et al, 2002;Pivot et al, 2003;Park et al, 2004).…”

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confidence: 99%

Phase II study of concurrent chemoradiotherapy with capecitabine and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck

et al. 2005

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We aimed to evaluate the efficacy and safety of concurrent chemoradiotherapy with capecitabine and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). In total, 37 patients with stage III or IV SCCHN were enrolled on the study. The chemotherapy consisted of two cycles of intravenous cisplatin of 80 mg m À2 on day 1 and oral capecitabine 825 mg m À2 twice daily from day 1 to day 14 at 3-week intervals. The radiotherapy (1.8 -2.0 Gy 1 fraction day À1 to a total dose of 70 -70.2 Gy) was delivered to the primary tumour site and neck. The primary tumour sites were as follows: oral cavity (n ¼ 6), oropharynx (n ¼ 11), hypopharynx (n ¼ 8), larynx (n ¼ 3), nasopharynx (n ¼ 6), and paranasal sinus (n ¼ 3). After the chemoradiotherapy, 29 complete responses (78.4%) and 6 partial responses (16.2%) were confirmed. Grade 3 or 4 neutropenia occurred only in two patients, plus grade 3 febrile neutropenia was observed only in one patient. At a median follow-up duration of 19.8 months, the estimated overall survival and progression-free survival rate at 2-year was 76.8 and 57.9%, respectively. Concurrent chemoradiotherapy with capecitabine and cisplatin was found to be well tolerated and effective in patients with locally advanced SCCHN.

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“…Oral fluorinated pyrimidines may mimic continuous regimens without its technical inconvenience and deterring patients' quality of life. In patients with advanced colorectal cancer, the efficacy of UFT (typical and most prescribed O-FP) plus oral LV (Carmichael et al, 2002;Douillard et al, 2002) or of capecitabine alone (Hoff et al, 2001;Van Cutsem et al, 2001) seems comparable in terms of the efficacy with significantly less significant severe haematologic toxicities and/or stomatitis. The risk of severe hand-foot syndrome is lower in UFT than with capecitabine, but the risk of severe diarrhoea and other gastrointestinal symptoms is higher in UFT and in UFT/oral LV treatment for Western patients.…”

Section: Meta-analysis Of Uft For Rectal Cancer J Sakamoto Et Almentioning

confidence: 99%

An individual patient data meta-analysis of adjuvant therapy with uracil–tegafur (UFT) in patients with curatively resected rectal cancer

et al. 2007

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Uracil -Tegafur (UFT), an oral fluorinated pyrimidine chemotherapeutic agent, has been used for adjuvant chemotherapy in curatively resected colorectal cancer patients. Past trials and meta-analyses indicate that it is somewhat effective in extending survival of patients with rectal cancer. The objective of this study was to perform a reappraisal of randomised clinical trials conducted in this field. We designed an individual patient-based meta-analysis of relevant clinical trials to examine the benefit of UFT for curatively resected rectal cancer in terms of overall survival (OS), disease-free survival (DFS), and local relapse-free survival (LRFS). We analysed individual patient data of five adjuvant therapy randomised clinical trials for rectal cancer, which met the predetermined inclusion criteria. These five trials had a combined total of 2091 patients, UFT as adjuvant chemotherapy compared to surgery-alone, 5-year follow-up, intention-to-treat-based analytic strategy, and similar endpoints (OS and DFS). In a pooled analysis, UFT had significant advantage over surgery-alone in terms of both OS (hazard ratio, 0.82; 95% confidence interval (CI), 0.70 -0.97; P ¼ 0.02) and DFS (hazard ratio, 0.73; 95%CI, 0.63 -0.84; Po0.0001). This individual patient-based meta-analysis demonstrated that oral UFT significantly improves both OS and DFS in patients with curatively resected rectal cancer.

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Oral Capecitabine Compared With Intravenous Fluorouracil Plus Leucovorin in Patients With Metastatic Colorectal Cancer: Results of a Large Phase III Study

Abstract: Oral capecitabine achieved an at least equivalent efficacy compared with IV 5-FU/LV. Capecitabine demonstrated clinically meaningful safety advantages and the convenience of an oral agent.

Cited by 941 publications

References 32 publications

Anti‐metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum

Anti‐metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum

Phase II study of concurrent chemoradiotherapy with capecitabine and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck

An individual patient data meta-analysis of adjuvant therapy with uracil–tegafur (UFT) in patients with curatively resected rectal cancer

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