A lower dose of oxaliplatin (Eloxatin) and capecitabine (Xeloda) had comparable efficacy and minimized adverse events (AEs) in elderly and frail patients with advanced gastroesophageal cancer, according to the GO2 study that will be presented at the 2019 ASCO Annual Meeting.
“The average age in the UK of a diagnosis of advanced gastroesophageal cancer is around 75 years of age, and many of these patients demonstrate frailty or suffer from medical comorbidities,” said study author Peter S. Hall, PhD, clinical senior lecturer in cancer informatics and health economics at the University of Edinburgh.
“Standard chemotherapy for these patients has been developed over a number of historical clinical trials which have predominantly included younger patients at an average age of about 65, who are usually free of medical comorbidities and have been selected to be without frailty.”
As a result, many elderly or frail patients with advanced gastroesophageal cancer are being treated with a wide range of chemotherapy regimens not backed by evidence, Hall explained. In the researcher’s earlier 321GO trial, a standard 3-drug regimen was compared with a 2-drug and a 1-drug regimen for this patient population.
“We found that the 2-drug regime had the best balance of benefits and harms in that phase 2 trial. So, we took forth that 2-drug regime in the setting of a large, phase III trial called GO2, which was a national trial conducted in the UK aiming to find the optimal dose levels of that regime, specifically in frail or elderly patients, with an emphasis in addressing the harms and benefits,” Hall said.
GO2 was a randomized, phase III trial designed to find the optimum dose of oxaliplatin, which inhibits DNA replication, plus capecitabine, which inhibits tumor cell division. Researchers also investigated optimal clinical benefit, tolerability, quality of life, and patient satisfaction for the drug duo to determine Overall Treatment Utility (OTU).
Trial participants were between the age of 51 and 96 and were randomly assigned to one of three dosage levels: Level A, 130 mg/m2
of oxaliplatin administered once ever 21 days and 625 mg/m2
of capecitabine twice a day, given continuously; Level B, which was 80% of the Level A dosage; and Level C, which was 60% of the Level A dosage. Patients who had decreased kidney function received 75% of the suggested dose of capecitabine.
Progression-free survival (PFS)–the primary endpoint–was comparable among the groups, at 4.9 months, 4.1 months, and 4.3 months for Levels A, B, and C, respectively.
After 9 weeks, the researchers found that patients randomized to the Level C dosage had fewer toxic reactions and better OTU outcomes than those in Levels A and B. Younger and less frail patients tended to have the best OTUs, and there was no patient group benefitted from the higher doses given in Level A. Level C patients also had a higher percentage of good OTU scores (43%) compared to 35% in Level A and 36% in Level B.
To achieve a good OTU, patients had to achieve 6 different domains, including: cancer not progressing on scans; lack of severe toxicity; global quality of life scores not deteriorating; patients scoring the treatment as being both worthwhile and not interfering with daily activities.
Overall survival (OS) was a secondary measure, and also did not vary much between the groups. Patients on Level A lived a median of 7.5 months; patients on Level B received an average of 6.7 months; and patients on Level C lived an average of 7.6 months.
When it came to toxicity, more than half (56%) of patients receiving Level A and B doses experienced severe, grade 3 or higher AEs, compared to only 37% of patients on the Level C doses.
“We found that the lowest dose tested was noninferior in terms of progression-free survival. It produced less toxicity and better overall treatment utility,” Hall said. “So we conclude that low-dose treatments may be offered to patients who are suitable for chemotherapy, but considered either too frail or elderly for a full-dose standard regime, with the confidence that it can produce superior outcomes without compromising cancer control or survival.”
Hall PS, Swinson D, Waters JS, Falk S, et al. Alternative chemotherapy for frail or elderly patients with advanced gastric or oesophageal cancer. Presented at: 2019 ASCO Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 4006.
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