Printer Friendly

How can we treat elderly patients with colorectal cancer?

There is a dramatic increase in the incidence of cancer with age and, over the next 20 years, the number of elderly patients with cancer will probably double. Colorectal cancer (CRC) is the second most common cancer and 40%of those with it are elderly patients over the age of 74 years [1]. The treatment of these patients is an important issue: life expectancy may be long in the absence of serious comorbidities, ranging from 7 to 9 years at 80 years, and illustrates the fact that there is no a priori reason to exclude this group from active treatments. However, comparisons in the Netherlands, USA and France [cf. 1,2] have shown that elderly patients are poorly represented in or excluded from clinical trials and receive less effective therapy for their cancer compared with younger patients. Hence, there are still many questions about the indications for, and the activity of, chemotherapy in this population. Kohne et al.'s [2] excellent review summarises this issue and gives a very candid and well-documented update on what is known about chemotherapy in elderly patients and the utility of scales and geriatric assessment.

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. [2] use the apparently simple classification proposed by Balducci and Extermann [3] 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 [4].

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 [5]. 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 [6].

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. [2] and Mitry and Rougier [7]. Adjuvant chemotherapy [8] as well as palliative chemotherapy for metastatic disease is active in elderly patients. 5-fluorouracil [9] as well as oxaliplatin [10] and irinotecan [11] 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 [12], 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 [13]. 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 [2] 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.

References

[1.] Mitry E, Benhamiche AM, Jouve JL et al. Colorectal adenocarcinoma in patients under 45 years of age: comparison with older patients in a well-defined French population. Dis Colon Rectum, 2001, 44, 380-387.

[2.] Kohne CH, Folprecht G, Goldberg RM et al. Chemotherapy in elderly patients with colorectal cancer. Oncologist, 2008, 13, 390-402.

[3.] Balducci L, Extermann M. Management of cancer in the older person: a practical approach. Oncologist, 2000, 5, 224-237.

[4.] Cudennec T, Moulias S, Lievre A et al. Elderly with cancer: identifying frailty, the real target of the oncogeriatrics team. Poster presentation (P-0294), 2007 World Congress of Gastrointestinal Cancer. Ann Oncol, 2007, 18 (Suppl 7), 106.

[5.] Aparicio T, Navazesh A, Boutron I et al. Half of elderly patients routinely treated for colorectal cancer receive a sub-standard treatment. Crit Rev Oncol Hematol, 2009, Jan 6 [epub ahead of print].

[6.] Balducci L, Beghe C. Cancer and age in the USA. Oncol Hematol, 2001, 37, 137-145.

[7.] Mitry E, Rougier P. Benefits and risks of chemotherapy in elderly patients with metastatic colorectal cancer. Aliment Pharmacol Ther, 2009, 29, 161-171.

[8.] Sargent D, Goldberg R, Macdonald J et al. Adjuvant chemotherapy for colon cancer (CC) is beneficial without significantly increased toxicity in elderly patients (Pts): results from a 3351 Pts metaanalysis. New Engl J Med, 2001, 345, 1091-1097.

[9.] Mabro M, Gilles-Amar V, Louvet C et al. Bimonthly 5-fluorouracil in elderly patients with metastatic colorectal cancer. Study of 50 patients. Rev Med Interne, 1999, 20, 863-868.

[10.] Tabah-Fish I, Maindrault-Goebel F, Benavides M et al. Oxaliplatin/5 FU/LV is feasible, safe and active in elderly colorectal cancer (CRC). Proc Am Soc Clin Oncol, 2002, 21, 140a.

[11.] Folprecht G, Seymour MT, Saltz L et al.; Irinotecan Meta-analysis Group. Irinotecan/5-FU/FA (I-FU) or 5-FU/FA (FU) first-line therapy in older and younger patients with metastatic colorectal cancer: combined analysis of 2691 patients in randomized controlled trials. J Clin Oncol, 2007, 25 (Suppl 18), 4071.

[12.] Bouchahda M, Macarulla T, Spano JP et al. Cetuximab efficacy and safety in a retrospective cohort of elderly patients with heavily pretreated metastatic colorectal cancer. Crit Rev Oncol Hematol, 2008, 67, 255-262.

[13.] Kabbinavar FF, Hurwitz HI, Yi J, Sarkar S, Rosen O. Addition of bevacizumab to fluorouracil-based first-line treatment of metastatic colorectal cancer: pooled analysis of cohorts of older patients from two randomized clinical trials. J Clin Oncol, 2009, 27, 199-205.

Correspondence to: Philippe Rougier (email: philippe.rougier@apr.aphp.fr)

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
COPYRIGHT 2009 Mediscript Ltd.
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2009 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Author:Rougier, Philippe; Cudennec, Tristan; Mitry, Emmanuel
Publication:Advances in Gastrointestinal Cancer
Article Type:Report
Geographic Code:4EUFR
Date:Mar 1, 2009
Words:1771
Previous Article:A retrospective study of bifractionated CPT-11 with LF5FU infusion (FOLFIRI-3) in colorectal cancer patients pretreated with oxaliplatin and CPT-11...
Next Article:Anti-epidermal growth factor receptor monoclonal antibodies (cetuximab or panitumumab) and chemotherapy in the treatment of metastatic colorectal...
Topics:

Terms of use | Privacy policy | Copyright © 2020 Farlex, Inc. | Feedback | For webmasters