McCleary NJ1, Meyerhardt JA, Green E, et al. Impact of age on the efficacy of newer adjuvant therapies in patients with stage II/III colon cancer: findings from the ACCENT database

Christopher J. Twelves, University of Leeds and St James's Institute of Oncology, Leeds, United Kingdom
Journal of Clinical Oncology (Impact Factor: 18.43). 06/2013; 31(20). DOI: 10.1200/JCO.2013.49.6638
Source: PubMed


PURPOSEPrior studies have suggested that patients with stage II/III colon cancer receive similar benefit from intravenous (IV) fluoropyrimidine adjuvant therapy regardless of age. Combination regimens and oral fluorouracil (FU) therapy are now standard. We examined the impact of age on colon cancer recurrence and mortality after adjuvant therapy with these newer options. PATIENTS AND METHODS
We analyzed 11,953 patients age < 70 and 2,575 age ≥ 70 years from seven adjuvant therapy trials comparing IV FU with oral fluoropyrimidines (capecitabine, uracil, or tegafur) or combinations of fluoropyrimidines with oxaliplatin or irinotecan in stage II/III colon cancer. End points were disease-free survival (DFS), overall survival (OS), and time to recurrence (TTR).ResultsIn three studies comparing oxaliplatin-based chemotherapy with IV FU, statistically significant interactions were not observed between treatment arm and age (P interaction = .09 for DFS, .05 for OS, and .36 for TTR), although the stratified point estimates suggested limited benefit from the addition of oxaliplatin in elderly patients (DFS hazard ratio [HR], 0.94; 95% CI, 0.78 to 1.13; OS HR, 1.04; 95% CI, 0.85 to 1.27). No significant interactions by age were detected with oral fluoropyrimidine therapy compared with IV FU; noninferiority was supported in both age populations. CONCLUSION
Patients age ≥ 70 years seemed to experience reduced benefit from adding oxaliplatin to fluoropyrimidines in the adjuvant setting, although statistically, there was not a significant effect modification by age, whereas oral fluoropyrimidines retained their efficacy.

Download full-text


Available from: Daniel Sargent, Nov 16, 2015
  • Source
    • "The addition of oxaliplatin provided a short-term reduction in the risk of recurrence, but after a period of time the OS benefit diminished as older patients died from other causes. It is therefore unclear as to which subset of older patients may derive benefit from oxaliplatin-based regimens [McCleary et al. 2013]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In a continuously aging population, the burden of colorectal cancer (CRC) is rising among older patients. Despite the fact that almost half of the cases occur in patients over 75 years, this age group is subjected to disparities regarding diagnostic and therapeutic options. So far, exclusion of older patients from randomized clinical trials has resulted in a lack of evidence-based guidelines. Nevertheless, newer data from studies specifically targeting older patients and subgroup analyses indicate that proper treatment planning and specific medical and geriatric assessment can achieve a safe and beneficial treatment result in older patients, often with similar outcomes to their younger counterparts. Resection of the primary tumour, if feasible, should be the primary goal of surgery aiming for cure, although it should be avoided under emergency conditions. Chronological age per se should not be an exclusion criterion for adjuvant or palliative chemotherapy, or targeted therapies. Careful patient selection, dose adjustments, close monitoring and early intervention in the event of side effects are essential. The benefits of treatment must be balanced with potential effects of treatment and patients' wishes.
    05/2014; 6(3):128-140. DOI:10.1177/1758834014523328
  • Source
    • ". Analysis of the ACCENT database, including 10,449 patients under 70 years and 2170 patients over 70 years from six randomized studies, demonstrated a significant interaction between age and treatment effect [Jackson McLeary et al. 2009]. No differences in outcomes were noted between experimental (combination) chemotherapy and fluoropyrimidine control chemotherapy in patients over 70 years. "
    [Show abstract] [Hide abstract]
    ABSTRACT: As the therapeutic options for the treatment of colorectal cancer have expanded over the past 20 years, so has the complexity of decision making. The goals of treatment in the palliative, adjuvant and neoadjuvant settings vary and it is not only the efficacy of drugs that influence treatment decisions. Age, performance status, the presence of significant comorbidities and the different treatment regimens and strategies provide medical oncologists with an array of options to attempt to maximize patients' quality of life and longevity.
    rapeutic Advances in Medical Oncology, The 01/2011; 3(1):43-52. DOI:10.1177/1758834010388342 · 2.83 Impact Factor
  • Source

Show more