The role of uracil-tegafur (UFT) in elderly patients with colorectal cancer
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
References (55)
- et al.
Oxaliplatin with high-dose leucovorin and 5-fluorouracil 48-hour continuous infusion in pretreated metastatic colorectal cancer
Eur. J. Cancer.
(1997) - et al.
Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer
Lancet
(1998) - et al.
Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer
Lancet
(1998) - et al.
Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial
Lancet
(2000) - et al.
Efficacy of oral tegafur modulation by uracil (UFT) and leucovorin in advanced colorectal cancer: a phase II study
Eur. J. Cancer.
(1995) - et al.
A phase I/II study of oral uracil/tegafur (UFT), leucovorin and irinotecan in patients with advanced colorectal cancer
Ann. Oncol.
(2003) - et al.
Patient preference and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin: a randomised crossover trial in advanced colorectal cancer
Eur. J. Cancer.
(2002) - et al.
Cancer in the elderly: why so badly treated?
Lancet
(1990) - et al.
Chemotherapy in elderly patients with colorectal cancer
Ann. Oncol.
(2001) - et al.
Cancer in older persons: magnitude of the problem—how do we apply what we know?
Cancer
(1994)
Are the elderly receiving appropriate treatment for cancer?
Ann. Oncol.
Medical treatment of colorectal cancer in elderly (>70 years): GISCAD experience and future perspectives
Tumori
A multivariate analysis of clinical and pathological variables in prognosis after resection of large bowel cancer
Br. J. Surg.
Cancer of the colon
Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: a French intergroup study
J. Clin. Oncol.
Multicenter phase II study of bimonthly high-dose leucovorin, fluorouracil infusion, and oxaliplatin for metastatic colorectal cancer resistant to the same leucovorin and fluorouracil regimen
J Clin Oncol.
Oxaliplatin plus 5-fluorouracil: clinical experience in patients with advanced colorectal cancer
Semin. Oncol.
Oxaliplatin: a new therapeutic option in colorectal cancer
Semin. Oncol.
Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer
J Clin Oncol.
Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer
J Clin Oncol.
N9741:oxaliplatin (oxal) or CPT-11 + 5-fluorouracil (5FU)/leucovorin (LV) or oxal+CPT-11 in advanced colorectal cancer (CRC). Initial toxicity and response data from a GI Intergroup study
Proc. Am. Soc. Clin. Oncol.
Phase III study of bolus 5-fluorouracil (5-FU)/ folinic acid (FA) (Mayo) vs. weekly high-dose 24 h 5-FU infusion/FA + oxaliplatin (OXA) (FUFOX) in advanced colorectal cancer (ACRC)
Proc. Am. Soc. Clin. Oncol.
FOLFIRI followed by FOLFOX versus FOLFOX followed by FOLFIRI in metastatic colorectal cancer (MCRC): final results of phase III study
Proc. Am. Soc. Clin. Oncol.
Irinotecan is an active agent in untreated patients with metastatic colorectal cancer
J Clin Oncol.
A phase III multicenter randomized study of CPT-11 versus supportive care (SC) alone in patients (Pts) with 5FU-resistant metastatic colorectal cancer (MCRC)
Proc. Am. Soc. Clin. Oncol.
Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group
N. Engl. J. Med.
Cited by (0)
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).