Current palliative chemotherapy trials in the elderly neglect patient-centred outcome measures

doi:10.1016/j.jgo.2014.09.181

Journal of Geriatric Oncology

Volume 6, Issue 1, January 2015, Pages 15-22

https://doi.org/10.1016/j.jgo.2014.09.181 Get rights and content

Abstract

Background

The elderly comprise the majority of patients newly diagnosed with cancer. Despite this, little evidence-based data are available on the care of the growing number of older patients with cancer. The objective of the current study was to evaluate the characteristics and outcome measures of current clinical trials on palliative chemotherapy in elderly patients.

Methods

Fourteen international clinical trials registries were searched using the terms “cancer” and “elderly” to identify clinical palliative chemotherapy trials designed specifically for patients aged 70 + years. From the trial protocol, data were extracted on trial characteristics and outcome measures.

Results

Of 127 trials, 81% formulated one or more stringent criteria with respect to organ function; 32% excluded patients with WHO performance status (PS) 2 and 83% with PS3. Functional outcomes, health care utilisation, cognitive function after treatment, and quality of life were reported in 6%, 3%, 6%, and 31% of trials, respectively. In only 16% of trials on palliative cancer treatment, a geriatric assessment was performed at baseline.

Conclusion

Although recent years have seen a growing evidence base regarding fit older patients, our study suggests a lack of representative cohorts of older patients and patient-centred outcome measures in current palliative treatment trials for the elderly. Research addressing alternative outcome measures, including quality of life and impact of therapy on general functioning, cognition, and preservation of independence, and incorporation of a geriatric assessment are needed to provide elderly patients with cancer and their treating physicians with realistic information about palliative chemotherapy.

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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Study objectives in clinical trials in older patients with solid malignancies: do we measure what matters?
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Current palliative chemotherapy trials in the elderly neglect patient-centred outcome measures

Abstract

Background

Methods

Results

Conclusion

Introduction

Section snippets

Methods

Results

Discussion

Conclusion

Disclosures and Conflict of Interest Statements

Author Contributions

Crit Rev Oncol Hematol

Ann Oncol

J Geriatr Oncol

Eur J Cancer

Eur J Oncol Nurs

J Geriatr Oncol

Eur J Cancer

Crit Rev Oncol Hematol

Cancer statistics 2009

CA Cancer J Clin

Participation of patients 65 years of age or older in cancer clinical trials

J Clin Oncol

Underrepresentation of patients 65 years of age or older in cancer-treatment trials

N Engl J Med