How can we treat elderly patients with colorectal cancer?
The main problem for the oncologist or gastroenterologist treating an elderly patient with an advanced CRC is to evaluate the benefits that may result from chemotherapy compared with its toxicity and risks to performance status (PS) and/or quality of life deterioration. To help in this evaluation, Kohne et al.  use the apparently simple classification proposed by Balducci and Extermann  who suggested a comprehensive geriatric assessment (CGA) that allows the practitioner to recognise at least three stages of ageing. Patients in Group 1, who are functionally independent and without comorbidity, are candidates for any form of standard cancer treatment, with the possible exception of bone marrow transplant. Those in Group 3 are frail with dependence in one or more activities of daily living, three or more comorbid conditions, and one or more geriatric syndromes and thus would be candidates for palliative treatment only. While those in Group 2 comprise people in between, who may benefit from some specific pharmacological approach, such as reduction in the initial dose of chemotherapy with subsequent dose escalations. This classification is very helpful. In our institution, these evaluations are conducted by a mobile geriatrics team (MGT) in selected cases, and this has been the case for the past 3 years. The MGT helps us to define a personalised medical plan and to determine which patients may receive chemotherapy .
Of 124 evaluations by our MGT of elderly patients (average age 79 [+ or -] 6 years) who presented with a digestive cancer, a spatial or temporal disorder was found in 30%, a probable depressive syndrome in 43% and the timed 'Get up and Go' test (functional autonomy) were 'normal', with a score lower than 20 seconds, in 60% of the cases. Seventy-seven of these 124 evaluations took place before the decision to start chemotherapy. However, in 34% of the cases there was little discussion because the patients had good PS, few comorbidities and were considered 'fit' and able to benefit from treatment of their cancer (Group 1). Similarly, for the 40% of the elderly patients judged to be frail (Group 3), little discussion was required and the patients were treated palliatively. In contrast, for the remaining 26% of the patients (Group 2) who had functional or intellectual frailty, a thorough geriatric evaluation was performed during a stay in the hospital geriatric department before any decision on treatment with chemotherapy was taken.
From this group of 'intermediate' patients (Group 2), 60% subsequently received chemotherapy following evaluation. The recommendations of the MGT ware taken for all but one patient and, in our experience, chemotherapy has been undertaken in approximately 50% of the elderly patients following the MGT evaluation and multidisciplinary discussion. In only one case was the MGT's proposal not followed by the service, because there was strong opposition from the patient and his family.
In practice, the help of the MGT may not be required for elderly patients who are functionally independent and without comorbidities (Group 1) because they are relatively easy to identify. These patients can receive chemotherapy without much increase in risk of toxicity. In the same way, 'frail', Group 3 elderly patients with severe comorbidities or geriatric syndromes can also be easily recognised. These patients would receive palliative treatments because they have a short life expectancy, no real demand for aggressive treatment and would gain little benefit from chemotherapy. The MGT is very useful for screening people who lie between these groups (Group 2) and for whom the decision to treat is a matter of discussion. There is, in most cases, good correlation between the proposals formulated by the MGT and the decisions on treatment taken by the oncologist. It is very important to be able to propose a strategy to patients and their relatives based on geriatric assessments . There are also many advantages in developing an MGT: once in place, it is always available, flexible and adaptable.
For those elderly patients excluded from further treatment, chemotherapy may be ruled out by specific characteristics rather than by age per se. A decrease in cognitive abilities, functional status and the existence of comorbidities put elderly patients at greater risk from toxicity with anti-cancer drugs. Ageing is associated with a progressive reduction in the functional reserve of multiple organ systems and reduced tolerance of physical, emotional, and social stress. However, multidimensional geriatric assessment before treatment decisions are made can take into account these changes in organ function .
Unfortunately, some clinicians reduce the dose of cytotoxic drugs to compensate for these age-related changes in function, in order to reduce the risk of severe toxicity. However, dose reductions may result in a loss of efficacy, and recommended doses should be used when possible, particularly after the second or third cycles where the treatment is well tolerated.
The results of chemotherapy for colorectal cancer in elderly patients have been partially explored and are detailed in Kohne et al.  and Mitry and Rougier . Adjuvant chemotherapy  as well as palliative chemotherapy for metastatic disease is active in elderly patients. 5-fluorouracil  as well as oxaliplatin  and irinotecan  have been used in elderly patients with good efficacy, similar to that seen in younger patients. However, only randomised trials may quantify this efficacy. The ongoing FFCD 0102 trial is exploring the benefits of polychemotherapy (FOLFIRI) compared with monotherapy (leucovorin or 5-fluororacil) as first-line treatment.
There are fewer data on the tolerance and efficacy of targeted therapies in elderly patients than there are for chemotherapy. There is indirect evidence that cetuximab may be used without a great increase in toxicity , which is in contrast to the evidence for bevacizumab use. Severe vascular (severe arterial hypertension, arterial embolism, cerebrovascular accident, myocardial infarction) or digestive complications (perforations or bleeding) have been reported in approximately one-third of the cases . Bevacizumab, and possibly other anti-angiogenic agents, may be used in elderly patients but only with careful follow-up to detect early complications.
The improvement in overall survival that has been reported for colon as well as for rectal cancer over the past 20 years is related to many factors. These include a lower stage at diagnosis, a decrease in the postoperative mortality rate and also the addition of adjuvant treatment and more active medical treatment, even for elderly patients. Many new data  confirm that age is less important than PS, autonomy and comorbidities for making the decision to start chemotherapy. Age alone is no longer a sufficient reason for withholding adjuvant or palliative treatment. Performance status is also an insufficient means to estimate the general condition of elderly patients and expert evaluation of an elderly patient's comorbidities, functional, social and mental status is required, as well as knowledge of his or her desire for aggressive cytotoxic treatment. There is a clear need for clinical trials for elderly patients that takes into account their different physiological profiles.
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Correspondence to: Philippe Rougier (email: firstname.lastname@example.org)
Philippe Rougier (1), Tristan Cudennec (2) and Emmanuel Mitry (1)
(1) Department of Hepato-Gastroenterology and Digestive Oncology and (2) Mobile Geriatrics Team, Hopital Ambroise Pare, 92100, Boulogne-Billancourt, and University of Versailles, UVSQ, France
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|Author:||Rougier, Philippe; Cudennec, Tristan; Mitry, Emmanuel|
|Publication:||Advances in Gastrointestinal Cancer|
|Date:||Mar 1, 2009|
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