The role of uracil-tegafur (UFT) in elderly patients with colorectal cancer

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Abstract

5-Fluorouracil (5-FU) administered in several schedules since its introduction in 1957 continues to be an integral part of standard first-line therapy for colorectal cancer. Continuous intravenous (i.v.) infusion appears to yield improved response rate and overall survival, with fewer adverse effects compared with i.v. bolus dosing.

However, these protracted infusions require portable infusion pumps and central venous lines, which are associated with complications (i.e. increased risk of infection and clotting and/or dislodgement of the catheter, increased risk of venous thrombosis).

Colorectal carcinoma is the second cause of death for tumour after lung cancer. About 70% of cases occur over 65 years and 50% or more affects people over 70. In clinical research age was a common exclusion criteria and little information is available about the efficacy, safety and toxicity of chemotherapy in elderly patients because few studies focused on the treatment of cancer in that part of population.

The goal of this article is to review the literature concerning the treatment of elderly patients with UFT, an orally administered dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine.

Introduction

There is a direct relation between cancer and aging because age is a major determinant of cancer risk. In many Western countries the life expectancy has increased significantly: up to now a quarter of Europeans is aged over 70 years and in the coming years more than 50% of all cancer patients will belong to that group of population [1].

In spite of the high prevalence of cancer in the elderly, little information is available about the efficacy, safety and toxicity of chemotherapy in elderly patients because few studies focused on the treatment of cancer in that part of population.

Until recently, advanced age was a common exclusion criteria in clinical trials: it has been calculated that among the most important trials concerning the treatment of colorectal cancer no more than 20% of patients are in the group of over 70 years [2].

A recent review of the literature has demonstrated that patients aged over 75 years represent only less than 2.5% of total patients enrolled for clinical trials for metastatic colorectal cancer.

In addition, according to same data about 70% of patients with colorectal cancer are aged 65 years or older [3] whereas the median age of people included in clinical trials is at least 10 years less.

Because older patients may not tolerate intensive chemotherapy and because concomitant medical conditions may preclude certain treatments, patients aged 70 years and older may be insufficiently staged and treated [4].

To evaluate the opportunity of treating an old patient with cancer we have to consider efficacy, tolerability and also socio-economic factors. In advanced disease it is also necessary to establish if the clinical benefit obtained with a specific treatment is superior to the results of the best supportive care. Clinical feasibility of a given therapy and its tolerability are influenced by biological modifications that occur in aging, particularly at the level of many organ functions [5].

The elderly may have several reasons that make more difficult to withstand chemotherapy (Fig. 1): a decreased renal, hepatic, respiratory and cardiac functions, a decreased bone marrow reserve, a different distribution and clearance of drugs and an increased probability of comorbidities.

There is a correlation between age and survival rate: the 5-year survival rate is 47% for patients with colorectal carcinoma younger than 60 years and 30% for those patients older than 60 years [6].

Colorectal cancer represents the fourth most common cancer in the world. Despite surgical resection, followed in certain subgroups of patients by adjuvant chemotherapy, 30–40% of patients with localized disease relapse and die from their cancer. A further 20–30% of patients have metastatic disease at the presentation [7].

Section snippets

CRC standard treatment

For a long time the standard treatments for advanced colorectal cancer in the United States was based on intravenous (i.v.) fluorouracil (5-FU) modulated by calcium leucovorin (LV) using the Mayo Clinic regimen (a 5-day schedule of 5-FU 370 to 425 mg/meq/day and LV 20 mg/meq/day repeated every 4–5 weeks). Some studies suggest that this association improves the response rate as compared with single-agent 5-FU but such an improvement has not been clearly translated into a survival advantage [8].

In

Conclusions

In conclusion, it is possible to assert that UFT regimen can be considered a well-grounded terapeutical option in patients not able to stand a combination treatment or in those patients in which, for several (psicological, clinical or compliance problems) reasons, oral treatment is preferable.

Oral agents may have the potential to enhance the quality of life also of elderly patients by enabling home-based therapy that avoids the discomfort, inconvenience, and pain associated with i.v. therapy

Roberto Labianca, head of Unit of Medical Oncology, Ospedali Riuniti di Bergamo, Degree in Medicine and Surgery on 1975, specialization in Medical Oncology on 1981, specialization in Allergology and Clinical Immunology on 1981. He is the national president of AIOM Association (Associazione Italiana di Oncologia Medica). His principal clinical research interests are in gastrointestinal cancer. He is a member of numerous international scientific societies including ESMO (European Society for

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    Roberto Labianca, head of Unit of Medical Oncology, Ospedali Riuniti di Bergamo, Degree in Medicine and Surgery on 1975, specialization in Medical Oncology on 1981, specialization in Allergology and Clinical Immunology on 1981. He is the national president of AIOM Association (Associazione Italiana di Oncologia Medica). His principal clinical research interests are in gastrointestinal cancer. He is a member of numerous international scientific societies including ESMO (European Society for Medical Oncology), ASCO (American Society of Clinical Oncology), MASCC (Multinational Association for Supportive Care of Cancer), EAPC (European Association of Palliative Care). He is a member of numerous scientific groups including GISCAD (Gruppo Italiano per lo Studio dei Carcinomi dell’Apparato Digerente), ITMO (Italian Trials in Medical Oncology), GIVIO (Gruppo Italiano per la valutazione degli Interventi in Oncologia), EORTC (European Organization for the Research and Treatment of Cancer), GITCLO (Gastrointestinal Tumour Cooperative Groups Liaison Office), IWGCRC (International Working Group for Colorectal Cancer).

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