Oxaliplatin- or irinotecan-based chemotherapy for metastatic colorectal cancer in the elderly

Service d'Hépato-Gastroentérologie, Hôpital Bichat-Claude Bernard, 46 rue Henri Huchard, AP-HP, Paris 75018, France.
British Journal of Cancer (Impact Factor: 4.84). 11/2003; 89(8):1439-44. DOI: 10.1038/sj.bjc.6601310
Source: PubMed


The tolerance and efficacy of oxaliplatin and irinotecan for metastatic colorectal cancer are unknown in elderly patients. Methods. All consecutive patients over 74 years treated with oxaliplatin or irinotecan for metastatic colorectal cancer were enrolled. The tumour response was assessed every 2-3 months and toxicity was collected at each cycle according to World Health Organisation criteria. A total of 66 patients were enrolled from 12 centres. The median age was 78 years (range, 75-88 years); 39 patients had no severe comorbidity according to the Charlson score. In total, 44 and 22 patients received oxaliplatin or irinotecan, respectively, in combination with 5-fluororuracil+/-folinic acid or raltitrexed in 64 patients. A total of 545 chemotherapy cycles were administered in first (41%), second (51%) or third line (8%). A dose reduction occurred in 190 cycles (35%). Complete response, partial response and stabilisation occurred in 1.5, 20 and 47% of patients, respectively. The median time to progression and overall survival were 6.8 and 11.2 months in first line and 6.3 and 11.6 months in second line, respectively. Grade 3 and 4 toxicity occurred in 42% of patients: neutropenia 17%, diarrhoea 15%, neuropathy 11%, nausea and vomiting 8% and thrombopenia 6%. There was no treatment-related death. In selected elderly patients, chemotherapy with oxaliplatin or irinotecan is feasible with manageable toxicity.

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    • "Studies have even indicated that comorbid illnesses prevalent in older patients with cancer could directly affect the cancer biology [25-27]. In addition, accumulating evidence suggests that chronic diseases may enhance the toxicity of chemotherapy and alter treatment responses [28] [29] [30]. The resulting heterogeneity in patients with cancer precludes the appropriate extrapolation of clinical trial results derived from younger or more selective older populations [14] [15] [19] [22]. "
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    ABSTRACT: A chronic disease in older adults usually runs a course that is less predictable than in younger individuals. Unexplained variations in disease incidence, prognosis, therapeutic responses, and toxicity are frequently observed among older adults. This heterogeneity poses huge challenges to the current one-size-fits-all health care systems, and calls for more personalized managements of chronic diseases in older adults. Aging is characterized by progressive deterioration of bodily functions with increasing risk of failure over time. The entire process is hierarchically organized, and progresses from intracellular events to changes at systemic and ultimately organism levels at different rates among different individuals. Aging biology exerts great influences on the development and progression of most age-related chronic diseases. Thus, aging biology could contribute to the complexity of illnesses that increase with age, and aging biomarkers possess a great potential to enable personalized health risk assessment and health care. We review evidences supporting the roles of aging biomarkers in risk assessment of prevalent age-related diseases. Frailty phenotype is an objectively measured indicator of advanced-stage aging that is characterized by organism-level dysfunction. In contrast, altered inflammation markers level signifies an earlier stage between cellular abnormalities and systems dysfunction. Results of human observational studies and randomized controlled trials indicate that these measures, albeit simple, greatly facilitate classification of older patients with cancer, chronic kidney disease, cardiovascular diseases and type 2 diabetes mellitus into groups that vary in disease incidence, prognosis and therapeutic response/toxicity. As the detailed mechanisms underlying the complex biologic process of aging are unraveled in the future, a larger array of biomarkers that correlate with biologic aging at different stages will be discovered. Following the translational research framework described in this article, these research efforts would result in innovations in disease prevention and management that address the huge unmet health needs of aging populations.
    03/2015; 5(1). DOI:10.7603/s40681-015-0001-1
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    • "Survival was also unaffected by age of patients. In another multicentre phase II study, it has been shown that chemotherapy with irinotecan or oxaliplatin-based treatment was feasible with manageable toxicity in the elderly (Aparicio et al, 2003). Similar data have also been found in firstline settings (Mitry et al, 2003; Rougier et al, 2003). "
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    ABSTRACT: Elderly patients are recommended to have a reduced starting dose (300 mg m(-2) once every 3 weeks) of irinotecan monotherapy. The aims of this analysis are to compare toxicity and survival according to age, performance status (PS), gender and prior radical pelvic radiotherapy (RT). The primary end points were overall survival and an irinotecan-specific toxicity composite end point (TCE) defined as the occurrence of grade 3 or 4 diarrhoea, neutropenia, febrile neutropenia, fever, infection or nausea and vomiting. Between 1997 and 2003, 339 eligible patients with advanced colorectal cancer (CRC) progressing on or within 24 weeks of completing fluoropyrimidine-based chemotherapy were prospectively registered in a multicentre randomised trial. All patients commenced irinotecan at 350 mg m(-2) once every 3 weeks. There were no differences in proportions of patients developing TCE by age (<70 vs > or =70 : 37.8 vs 45.8%; P=0.218), PS (0-1 vs 2 : 39.3 vs 41.5%; P=0.793) or prior RT (RT vs no RT : 45.1 vs 38.5%; P=0.377). Males experienced more toxicity than females (44.3 vs 32.6%; P=0.031), but this was not significant after controlling for other co-variates (P=0.06). Patients aged > or =70 had similar objective responses (11.1 vs 9%; P=0.585) and survival (median 9.4 vs 9 months; log rank P=0.74) compared to younger patients. Elderly patients derive the same benefit without experiencing more toxicity with second-line irinotecan treatment for advanced CRC. Our data do not support the recommendation to reduce the starting dose for the elderly patients.
    British Journal of Cancer 10/2004; 91(8):1453-8. DOI:10.1038/sj.bjc.6602169 · 4.84 Impact Factor
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    • "Overall, an ORR of 21.5%, median PFS 6.8 months and median OS 11.2 months were reported in the first-line setting. There was significant toxicity: 42% of patients experienced grade 3/4 toxicity; neutropenia 17%, diarrhoea 15%, neuropathy 11%, nausea 8% and thrombocytopenia 6% (Aparicio et al, 2003). In our study, 30 (32.6%) patients were X74 years and there were relatively few grade 3/4 toxicities observed and minimal myelosuppression. "
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    ABSTRACT: This study was designed to assess the safety and efficacy of capecitabine and mitomycin C (MMC) in previously untreated patients with advanced colorectal cancer (CRC). Patients received capecitabine 2500 mg m(2) day 1, orally divided in two doses of 1250 mg m(-2) in the morning and evening for 14 days every 21 days and MMC 7 mg m(-2) (maximum total dose 14 mg) as an intravenous bolus every 6 weeks for a total of four courses. The median age was 70 years (range 24-85) and the majority of patients (86.9%) were of performance status 1/2. The most common metastatic site was liver. In all, 84 patients were assessable for response. The overall response rate was 38% (95% CI: 27.7-49.3) and a further 33.3% of patients achieved stable disease over 12 weeks. There was good symptom resolution ranging from 64 to 86%. Grade 3/4 toxicity was as follows: hand-foot syndrome 19.7%; diarrhoea 10%; neutropenia 2.4%; infection 2.3%. Capecitabine and MMC have shown encouraging activity with a favourable toxicity profile, a convenient administration schedule, and could be considered for patients deemed unsuitable for oxaliplatin and irinotecan combinations.
    British Journal of Cancer 09/2004; 91(5):839-43. DOI:10.1038/sj.bjc.6602039 · 4.84 Impact Factor
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