Cancer Research UK Edinburgh Centre

Optimizing treatment for the older and frailer cancer patients

Study with important contributions from Edinburgh investigators finds that less chemotherapy is noninferior to more in frail and elderly patients with advanced gastroesophageal cancer: May 2021

Schematic of the human digestive system

The food pipe (oesophagus) and stomach are part of the upper gastrointestinal (digestive) system. In Europe and North America, gastroesophageal cancers are the third-commonest cause of cancer death. These cancers are more frequent in older people who are often too frail to undergo full course of chemotherapy. There is no standard of care for the treatment of advanced gastroesophageal cancer in the United Kingdom, and practices vary widely as to which regimen is used.

In order to find the best way to treat people with cancer of the stomach or oesophagus who are not well enough for standard chemotherapy a clinical trial, known as GO2 phase III trial, has been designed. This trial brought together researchers and clinicians from multiple centres in the UK to assess whether older and/or frail patients with advanced gastroesophageal cancer benefit from less intensive palliative chemotherapy and whether a formal Geriatric Assessment can assist treatment decision-making.

The GO2 trial is the largest randomised controlled trial to date investigating frail and/or elderly. The trial was open for people to join between 2014 and 2017. It is supported by Cancer Research UK and led by Dr Peter Hall (CRUK Edinburgh Centre) and Professor Matt Seymour (University of Leeds) acting as Chief Investigators. The trial was run by the University of Leeds Clinical Trials Unit. It compared effects of three different dose levels of chemotherapy with oxaliplatin/capecitabine (level A: oxaliplatin at 130 mg/m2 given on day 1 every 21 days and capecitabine at 625 mg/m2 given twice daily on days 1 to 21; level B: 80% of level A doses; and level C: 60% of level A doses) using Overall Treatment Utility (OTU) assessment tool to help determine the outcomes.

Some of the results from the trial have been recently published in the journal JAMA Oncology. The article titled “Efficacy of Reduced-Intensity Chemotherapy With Oxaliplatin and Capecitabine on Quality of Life and Cancer Control Among Older and Frail Patients With Advanced Gastroesophageal Cancer - The GO2 Phase 3 Randomized Clinical Trial” presents evidence that reduced-intensity chemotherapy provides a better patient experience without significantly compromising cancer control and should be considered for older and/or frail patients. Baseline geriatric assessment can help predict the utility of chemotherapy but did not identify a group benefiting from higher-dose treatment. These results met with great interest among the oncologists worldwide and are likely to be practice-changing.

This is the largest randomized controlled trial to date specifically investigating frail and/or elderly patients with advanced gastroesophageal cancer, and the results should guide future treatment. We hope our findings will help patients make an informed choice between low-dose chemotherapy and no chemotherapy at all, with the knowledge that low-dose chemotherapy may prove beneficial and still allow them to maintain some quality of life while slowing the progression of the disease.

Dr Peter HallUniversity of Edinburgh

Related Links

Article in JAMA Oncology: https://jamanetwork.com/journals/jamaoncology/fullarticle/2780033

Commentary on the GO2 trial by Monica M. Bertagnolli (Harvard Medical School): https://ascopost.com/issues/may-25-2019/study-finds-less-chemotherapy-noninferior-to-more-in-frail-and-elderly-patients-with-advanced-gastroesophageal-cancer/

Commentary on the GO2 trial by Armin Shahrokni (Memorial Sloan Kettering Cancer Center): https://ascopost.com/issues/may-25-2019/epov-armin-shahrokni/

Information about GO2 phase III clinical trial: https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-chemotherapy-for-people-with-advanced-cancer-of-the-stomach-or-food-pipe-go2

Dr Peter Hall profile: https://www.ed.ac.uk/profile/peter-hall

Prof Matt Seymour profile: https://medicinehealth.leeds.ac.uk/medicine/staff/3085/professor-matt-seymour

Information about oesophageal cancer: https://www.cancerresearchuk.org/about-cancer/oesophageal-cancer

Information about stomach (gastric) cancer: https://www.cancerresearchuk.org/about-cancer/stomach-cancer