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2019 ASCO: Reduced Chemotherapy Dosages in Elderly Patients With Advanced Gastroesophageal Cancer

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Key Points

  • A lower-dose combination of oxaliplatin and capecitabine was more tolerable and as effective as higher doses of the chemotherapies in elderly patients with advanced gastroesophageal cancer. 
  • The results from this study should guide future treatment of advanced gastroesophageal cancer in elderly patients.

A phase III randomized clinical study evaluating the optimum dose of a combination chemotherapy regimen of oxaliplatin and capecitabine in the treatment of advanced gastroesophageal cancer in frail and elderly patients has found that the patients prescribed the lowest dose tested experienced less toxicity and had noninferior progression-free survival compared with those patients prescribed the higher doses of the combination therapy. When analyzed by age, frailty, and poor performance status, the lowest combination dose produced the best overall treatment utility even in younger, less frail patients with better performance status. The study by Hall et al will be presented during the 2019 ASCO Annual Meeting (Abstract 4006). 

Study Methodology

The researchers enrolled 514 patients into the study between 2014 and 2017 at cancer centers in the United Kingdom. Patients with gastroesophageal cancer were eligible if they could not tolerate full doses of the combination chemotherapy regimen epirubicin, oxaliplatin, and capecitabine due to age or frailty, but were fit for a combination of oxaliplatin and capecitabine chemotherapy. Baseline assessment included quality of life, symptoms, functional scales, comorbidity, and frailty.

The patients were randomly assigned 1:1:1 to three groups: dose level A (oxaliplatin at 130 mg/m2d1 and capecitabine at 625 mg/mdaily on days 1–21, every 21 days); level B (80% of level A doses); or level C (60% of level A doses). The study participants were scored for overall treatment utility at 9 weeks and thereafter, based on clinical judgement. Baseline fitness was assessed as predictive of overall treatment utility, overall, and by interaction with dose level.

Study Results

The researchers confirmed the noninferiority of progression-free survival for level B chemotherapy doses vs level A doses (hazard ratio [HR] = 1.09, confidence interval [CI] = 0.89–1.32) and for level C vs level A (HR = 1.10, CI = 0.90–1.33). Level C patients had less toxicity and better overall treatment utility outcomes than patients receiving level A or B chemotherapy doses.

When analyzed by baseline age, frailty, and poor performance status, level C chemotherapy doses produced the best overall treatment utility outcome even in patients who were younger, less frail, and had better performance status. No group was identified who benefited more from the higher-dose levels.

“This is the largest [randomized clinical trial] to date specifically investigating frail and/or elderly patients [with] advanced-stage gastroesophageal cancer, and [the findings] should guide future treatment. The lowest dose tested was noninferior in terms of progression-free survival and produced less toxicity and better overall treatment utility,” concluded the study authors. 

“Previous trials of palliative chemotherapy for gastric and esophageal cancer have not included frail or older patients. Therefore, the benefit of chemotherapy in these groups was unknown,” said lead study author Peter S. Hall, PhD, a medical oncologist at the University of Edinburgh, United Kingdom. “We hope our finding helps patients make a more informed choice, between low-dose chemotherapy and no chemotherapy at all, with the knowledge that that low-dose chemotherapy can prove beneficial and still allow patients to maintain some quality of life while slowing the progression of the disease.”

Disclosure: Funding from this study was provided by Cancer Research UK. For full disclosures of the study authors, visit asco.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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