Comparison of Oral Capecitabine Versus Intravenous Fluorouracil Plus Leucovorin as First-Line Treatment in 605 Patients With Metastatic Colorectal Cancer: Results of a Randomized Phase III Study

Hoff, Paulo M.; Ansari, Rafat; Batist, Gerald; Cox, John V.; Kocha, Walter; Kuperminc, Mario; Maroun, J.; Walde, David; Weaver, C. B.; Harrison, Evelyn B.; Burger, Hans Ulrich; Osterwalder, B; Wong, Alfred; Wong, R.

doi:10.1200/jco.2001.19.8.2282

Cited by 1,044 publications

(576 citation statements)

References 38 publications

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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: 94%

“…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.…”

Section: Abstract: Capecitabine; Lymph Node Metastasis; Lung Metastamentioning

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: 94%

Section: Abstract: Capecitabine; Lymph Node Metastasis; Lung Metastamentioning

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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“…Capecitabine and UFT/folinic acid already proved to be as effective as intravenous bolus 5-FU/folinic acid regimens Hoff et al, 2001;Van Cutsem et al, 2001), achieving response rates of 18.9 -24.8 and 12%, respectively, with less toxicity than with the 5-FU regimens. S-1 will have to be compared to those products in randomised studies to determine which oral fluoropyrimidine achieves the best results and the least toxicity.…”

Section: Discussionmentioning

confidence: 99%

EORTC Early Clinical Studies Group early phase II trial of S-1 in patients with advanced or metastatic colorectal cancer

et al. 2003

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Cancer of the colon and rectum is one of the most frequent malignancies both in the US and Europe. Standard palliative therapy is based on 5-fluorouracil/folinic acid combinations, with or without oxaliplatin or irinotecan, given intravenously. Oral medication has the advantage of greater patient convenience and acceptance and potential cost savings. S-1 is a new oral fluorinated pyrimidine derivative. In a nonrandomised phase II study, patients with advanced/metastatic colorectal cancer were treated with S-1 at 40 mg m À2 b.i.d. for 28 consecutive days, repeated every 5 weeks, but by amendment the dose was reduced to 35 mg m À2 during the study because of a higher than expected number of severe adverse drug reactions. In total 47 patients with colorectal cancer were included. In the 37 evaluable patients there were nine partial responses (24%), 17 stable diseases (46%) and 11 patients had progressive disease (30%). Diarrhoea occurred frequently and was often severe: in the 40 and 35 mg m À2 group, respectively, 38 and 35% of the patients experienced grade 3 -4 diarrhoea. The other toxicities were limited and manageable. S-1 is active in advanced colorectal cancer, but in order to establish a safer dose the drug should be subject to further investigations.

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“…Over the past 10 years, there has been an increasing use of capecitabine monotherapy and capecitabine-based combination regimens in the treatment of mCRC, which has been due, in large part, to the convenience and increased patient preferences for oral chemotherapy [50–54]. Randomized studies have shown that capecitabine-based treatments are associated with equal clinical efficacy and reduced toxicities when compared to infusional 5-FU regimens [50–54].…”

Section: -Fu Tdm With Capecitabinementioning

confidence: 99%

“…Randomized studies have shown that capecitabine-based treatments are associated with equal clinical efficacy and reduced toxicities when compared to infusional 5-FU regimens [50–54]. Finally, several pharmacoeconomic studies have demonstrated that capecitabine-based chemotherapy is associated with significant cost savings when compared to infusional 5-FU chemotherapy, and these economic benefits are seen for the adjuvant therapy setting as well as for the treatment of metastatic disease [55–59].…”

Section: -Fu Tdm With Capecitabinementioning

confidence: 99%

Therapeutic drug monitoring of 5-fluorouracil

Lee

Beumer

Chu

2016

Cancer Chemother Pharmacol

172

147

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Purpose For over 50 years, 5-FU has played a critical role in the systemic chemotherapy of cancer patients. 5-FU serves as the main backbone of combination chemotherapy for patients with colorectal cancer (CRC) in both the adjuvant and metastatic disease settings. Herein, we review the current status of 5-FU therapeutic drug monitoring (TDM) and discuss its potential role in the clinical practice setting. Method PubMed and abstracts from the American Society of Clinical Oncology (ASCO) were searched up through September 2015 for clinical data relating to 5-FU TDM. Results 5-FU dosing has been typically determined by using body surface area (BSA). However, it is now well-established that BSA-based 5-FU dosing is correlated with a wide variation of 5-FU systemic exposure. Pharmacokinetic (PK) studies of 5-FU systemic exposure have shown a wide range of interpatient variation of 5-FU plasma drug levels. Over the past 30 years, increasing efforts have been placed on optimizing 5-FU dosing with the main goals of increasing antitumor efficacy while reducing drug-associated toxicity. There is growing evidence to show that 5-FU dosing based on plasma 5-FU drug level is feasible and that 5-FU TDM can improve clinical outcomes by improving efficacy of 5-FU-based combination regimens and reducing toxicities. Conclusion Dose adjustment of 5-FU is feasible and PK-based dosing can significantly improve clinical outcomes by reducing toxicities and improving efficacy.

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Comparison of Oral Capecitabine Versus Intravenous Fluorouracil Plus Leucovorin as First-Line Treatment in 605 Patients With Metastatic Colorectal Cancer: Results of a Randomized Phase III Study

Cited by 1,044 publications

References 38 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

EORTC Early Clinical Studies Group early phase II trial of S-1 in patients with advanced or metastatic colorectal cancer

Therapeutic drug monitoring of 5-fluorouracil

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