Current palliative chemotherapy trials in the elderly neglect patient-centred outcome measures
Introduction
It is well-known that the population in industrialized countries is ageing. In the Netherlands, 7% of the population aged 75 years or older and this will double to about 15% by 2040 [1], [2]. The percentage of the population in the United States aged ≥ 80 years is even projected to increase from 10% in 2013 to 32% in 2050 [3]. As increasing age is directly associated with an increasing incidence of cancer, elderly comprise the majority of patients newly diagnosed with cancer. Over 60% of diagnosed cancer cases and nearly 80% of cancer deaths are observed in people over 60 years of age [4].
Optimal cancer care for the older patient preferably finds the balance between overtreatment and undertreatment and should take account of goals of care as well as disease-related factors [5], [6]. However, little is known about the optimal treatment for the older patients because they have been underrepresented in clinical trials [7], [8]. Moreover, treating older patients with cancer can be challenging due to the presence of comorbid conditions and impaired functional status [5], which can have significant impact on how patients tolerate treatment and their quality of life after treatment [9].
Existing trials focus on optimal cancer treatment based on disease-related factors incorporated in treatment guidelines, which may not be of greatest interest for the older patient [10], [11]. Traditional primary and secondary outcomes in cancer trials are progression-free and overall survival [9]. Additional outcomes, such as impact of therapy on general functioning, cognition and preservation of independence represent a large part of quality of life for the older patient and are of similar or even greater importance than gain in survival [11], [12], [13], [14].
At present, the number of patients receiving chemotherapy in the last months of life is increasing [15], [16]. In a palliative setting, the primary focus should be on the quality of life during and after treatment. Better understanding of those outcome measures that are most relevant to elderly patients, and the impact of geriatric impairments such as depression, falling, poor nutrition, and care dependence, will help clinicians and patients weigh potential risks and benefits of treatment and allow patients and families to prepare for the impact of cancer therapy.
Evidence on these aspects is currently scarce and therefore, progress is likely to come from ongoing clinical trials. To address this question, we evaluated the characteristics and outcome measures of current clinical trials on palliative chemotherapy in older patients with cancer.
Section snippets
Methods
On January 30, 2013, we performed an extensive search of clinical trial registries to identify cancer trials. The search included the North American National Institutes of Health clinical trial registry (www.clinicaltrials.gov), as well as the fourteen individual registries included in the International Clinical Trials Registry Platform (ICTRP) of the World Health organisation (http://www.who.int/ictrp), which focuses primarily on Europe, Asia and Africa. First, to identify all cancer trials,
Results
The trial registry search identified over 27,000 clinical trials in 14 different registries (Figure 1). Of these, 127 trials focused specifically on palliative chemotherapy in patients older than 70 years.
The study characteristics of these trials are summarized in Table 1. The trials covered 14 different diagnoses, with the most frequent being lung cancer (53%), colorectal cancer (12%), breast cancer (6%), and haematological malignancies (12%). Phase II trials comprised the vast majority of
Discussion
In this overview of 127 studies designed specifically for older patients with cancer with a palliative treatment intent, we found that the primary focus is still on disease-related outcome measures, such as overall and progression free survival, efficacy and toxicity. Despite the fact that these trials focus exclusively on palliative treatment, only one-third addresses quality of life. The completion of treatment, functional-, and cognitive outcomes were included in 7%, 6%, and 6% of these
Conclusion
Until now strikingly few studies on palliative chemotherapy include representative cohorts of elderly patients or focus on outcome measures most relevant to older patients with cancer. Although recent years have seen a growing evidence base regarding fit older patients, such trials are unlikely to provide answers to the many questions that remain regarding cancer treatment in the vulnerable older population. With limited data on which to base clinical decisions, especially among vulnerable
Disclosures and Conflict of Interest Statements
The authors have no conflicts of interest to disclose.
Author Contributions
Study Concept: ME Hamaker
Study Design: ME Hamaker, ML van Bekkum
Data Acquisition: ML van Bekkum
Quality Control of Data and Algorithms: ML van Bekkum, ME Hamaker
Data Analysis and Interpretation: ML van Bekkum, ME Hamaker
Statistical Analysis: ML van Bekkum, ME Hamaker
Manuscript Preparation: ML van Bekkum, ME Hamaker
Manuscript Editing and Review: ML van Bekkum, BC van Munster, PLM Thunnissen, CH Smorenburg, M.E. Hamaker
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