Reduced-Intensity Chemotherapy in Older, Frail Patients With Gastroesophageal Cancer

Senior woman with cancer, closed eyes, close up footage
Investigators aimed to determine optimal chemotherapy dosing for older, frail patients with gastroesophageal cancer and use of geriatric assessment as a decision making tool.

Reducing the intensity of palliative chemotherapy may improve patient experience in frail and older adults with advanced gastroesophageal cancer without significantly altering cancer control, according to study results published in JAMA Oncology.

A team of investigators conducted a randomized controlled phase 3 clinical trial (GO2; Identifier: ISRCTN44687907) of palliative chemotherapy with oxaliplatin and capecitabine. The study cohort included frail and older patients with advanced gastroesophageal cancer who were not eligible to receive standard full-dose chemotherapy but were suitable for lower-dose therapy. They aimed to determine what dosage was most suitable for this patient group and whether a formal geriatric assessment could aid in decision-making for treatment options.

The multicenter, noninferiority, open-label study included 2 randomizations. The first, aimed to compare 3 doses of oxaliplatin and capecitabine: levels A, B, and C. Level A was 130 mg/m2 of oxaliplatin on day 1 with 625 mg/m2 capecitabine twice a day on days 1 to 21, on a 21-day cycle. Levels B and C were 0.8 and 0.6 times the dosage of level A, respectively. The second randomization of the trial compared level C with the best supportive care.

Main study outcomes were progression-free survival and overall survival, as well as the overall treatment utility, which included: efficacy, toxicity, quality of life, and patient value/acceptability.

A total of 514 patients were included in the first randomization of the study; 75% of patients were men, 58% were severely frail, and the median patient age was 76 years. Of the cohort, 170 patients were treated with level A, 171 patients were treated with level B, and 173 patients were treated with level C.

Using level A as a reference dose, broad noninferiority of level B and C for progression-free survival were confirmed (hazard ratios [HRs] for level B and C, 1.09 and 1.10, respectively). The overall treatment utility and toxic effects were better in level C as compared with levels A and B; no patient subgroups benefited from higher doses.

In the secondary analysis, which included 45 patients, 23 patients were treated with level C chemotherapy, while 22 patients comprised the best supportive care cohort. Patients in the level C group had a longer overall survival compared with the best supportive care group. However, results were not significant (median overall survival, 6.1 vs 3.0 months, respectively; HR, 0.69; P =.34).

Using data from 522 patients with all available variables, multivariate analysis results suggested that baseline frailty, quality of life, and neutrophil to lymphocyte ratio were all independently linked to overall treatment utility, and can be collectively used in a model to predict the probability of different outcomes in this patient demographic.

The main limitation of this study was its solely observational geriatric assessment of patients.

“Careful baseline geriatric health assessment in the oncology clinic can help predict the likelihood of achieving those goals, and so contribute to patients’ and clinicians’ treatment decisions,” wrote the authors. “Assessing the outcome of cancer treatment should be multidimensional, including its value to patients and its adverse effects, and we recommend further development of [overall treatment utility] to capture this complexity,” the investigators noted.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Hall PS, Swinson D, Cairns DA, et al; GO2 Trial Investigators. 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. JAMA Oncol. Published online May 13, 2021. doi: 10.1001/jamaoncol.2021.0848