A low-dose chemotherapy regimen appears safe and effective for older and frail patients with advanced gastroesophageal cancer.
In a phase 3 trial, progression-free survival in patients who received the lowest dose of oxaliplatin and capecitabine was noninferior to progression-free survival in patients who received two higher doses of the combination.
The lowest dose also was associated with better overall treatment utility, which is a composite of clinical benefit, tolerability, quality of life, and patient value.
“[T]his is the largest randomized, controlled trial to date specifically investigating frail or elderly patients with advanced gastroesophageal cancer,” said study investigator Peter S. Hall, PhD, of the University of Edinburgh. “We found that the lowest dose tested was noninferior in terms of progression-free survival, it produced less toxicity, and it had better overall treatment utility.”
These findings are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology. Dr. Hall discussed the findings during a press briefing in advance of the meeting.
The phase 3 trial (ISRCTN44687907) enrolled older and frail patients, aged 51-96 years, with advanced gastroesophageal cancer. Dr. Hall presented data on 514 patients randomized to receive oxaliplatin and capecitabine at one of three dose levels. Dose level A consisted of oxaliplatin given at 130 mg/m2 once every 21 days and capecitabine given at 625 mg/m2 twice a day every day. Dose level B was 80% of the level A dosage, and dose level C was 60% of the level A dosage. Patients with decreased kidney function received 75% of the allocated capecitabine dose.
The trial’s primary endpoint was noninferiority of progression-free survival at 12 months. Noninferiority was confirmed for level B, compared with level A, with a hazard ratio of 1.09, and for level C, compared with level A, with a hazard ratio of 1.10.
“The lowest dose, the level C dose, had the best overall treatment utility … compared to patients either on level A or level B, and this was due to lower side effects and better quality of life,” Dr. Hall said.
Overall treatment utility outcomes were “good” in 35% of the dose A group, 36% of the dose B group, and 43% of the dose C group. Outcomes were “poor” in 31%, 38%, and 29%, respectively, and outcomes were “intermediate” in 34%, 26%, and 27%, respectively.
To achieve “good” overall treatment utility, patients had to achieve the following six domains: cancer doesn’t progress on scans, oncologist assesses a benefit of treatment, lack of severe toxicity, patient’s global quality of life scores aren’t deteriorating, patient scores the treatment as worthwhile, and the patient says the treatment doesn’t interfere with daily activities.
These results suggest low-dose chemotherapy is feasible for older and frail patients with advanced gastroesophageal cancer, according to Dr. Hall.
“[L]ow-dose treatment may be offered to patients who are suitable for chemotherapy but considered too frail or elderly for a full-dose standard regime, in the confidence that it can produce superior outcomes without compromising cancer control or survival,” Dr. Hall said.
Dr. Hall reported relationships with Eisai, Pfizer, Roche, AstraZeneca, Daiichi Sankyo, and Novartis. The trial was funded by Cancer Research UK and sponsored by the University of Leeds (England).
SOURCE: Hall PS et al. ASCO 2019, Abstract 4006.