Palliative chemotherapy in elderly patients with metastatic colorectal cancer: Do we know how it should be used?

Colorectal cancer is common in elderly patients, and approximately 40% of the patients are 75 years or older. Elderly patients have an inferior outcome compared to younger patients and adjuvant chemotherapy receipt is inversely associated with age [1 – 3]. In metastatic colorectal cancer (mCRC), median survival is lower in chemotherapy treated elderly patients from a general population [4 – 6]. An improvement in survival over time is seen among mCRC patients aged 70 or younger, whereas survival among patients  70 remains rather constant [6]. Palliative treatment of mCRC patients has rapidly evolved with introduction of new chemotherapeutics and targeted agents during the past about 15 years. There is an ongoing discussion whether elderly patients are undertreated, and an increasingly number of reports have focused on the effects of chemotherapy in elderly patients [7]. Chemotherapy is used more rarely in elderly patients. In a recent Scandinavian population-based study, 86% of mCRC patients  65 years received palliative chemotherapy, 63% when aged 70 – 75 years and only 40% when  75 years [4]. When given chemotherapy, elderly patients less often receive the more effective combination chemotherapy [4,8 – 9]. Due to concerns on toxicity, the chemotherapy dose is often reduced in elderly in routine clinical practice. Nearly 50% of elderly patients diagnosed with cancer received dose-intensity less than 85% of standard treatment, which may undermine outcome [10]. The use of palliative chemotherapy in mCRC has increased over time in all age groups. In a Dutch registry study the use of chemotherapy increased from 37% to 76 % in patients aged 70, whereas it increased from 12% to 36% in patients aged  70 [6]. The reduced use of chemotherapy in elderly could be attributed to a rejection for chemotherapy, however, studies have shown that elderly patients have the same willingness to receive chemotherapy as younger age groups [11]. Medical oncologists have gradually started to appreciate that the approach to cancer chemotherapy adopted for otherwise healthy adults cannot automatically be applied to older patients with age-related changes in physiology, reduced homeostatic reserve, and co-morbid medical problems. In an article in this issue of Acta Oncologica by Venderbosch et al., outcome of fi rst-line chemotherapy in elderly was compared to younger mCRC patients in a retrospective analysis of the CAIRO studies [12]. Capecitabine monotherapy resulted in a higher number of grade 3 – 4 toxicity. No signifi cant survival differences were seen, and the authors conclude wisely that similar results can be expected in general practice when trial eligibility criteria are applied . The study illustrates the problem of underrepresentation of elderly patients in clinical studies. Of the 1171 patients included, 208 patients (18%) were aged 70 – 75 and only 72 patients (6%) were above 75 of age. Many of the elderly patients included in these studies have been selected on the basis of good performance status and normal organ status, and are thus not representative of elderly patients treated in routine practice. In mCRC studies, median survival now regularly exceeds 20 months and approaches 30 months in selected studies, which implies a dramatic improvement compared with historical series reporting median survival of less than six months in untreated patients [13 – 15]. Median age in 143 mCRC studies during 2001 – 2005 was 62 [16], compared to a median age of 71 – 74 at diagnosis in cancer registries. In a population-based study, mCRC trial patients were younger, had better Acta Oncologica, 2012; 51: 819–821