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A modified regimen of docetaxel, cisplatin and fluorouracil appeared associated with improved efficacy and lower rates of toxicity than the standard regimen for patients with metastatic gastric adenocarcinoma, according to the results of a randomized phase 2 study.

“Gastric cancer remains a prevalent worldwide malignancy with a high mortality rate,” Manish A. Shah, M.D., Bartlett Family associate professor in gastrointestinal oncology and associate professor of medicine at Weill Cornell Medicine, and colleagues from the U.S. Gastric Cancer Consortium wrote. “Nearly 1 million people are diagnosed annually with the disease, and approximately 730,000 patients will die as a result annually.”

Docetaxel, cisplatin and fluorouracil (DCF) serves as the standard first-line chemotherapy regimen for advanced gastric or gastroesophageal junction (GEJ) cancer; however, it is associated with high toxicity rates.

Shah and colleagues sought to determine the safety and efficacy of a modified DCF regimen in 85 patients (median age, 58 years; female, n = 24) with metastatic GEJ (n = 28) or gastric adenocarcinoma (n = 57)

They randomly assigned 54 patients to modified DCF (2,000 mg/m2 IV fluorouracil every 48 hours; 40 mg/m2 IV docetaxel on day 1; 40 mg/m2 IV cisplatin on day 3; every 2 weeks) and 31 patients to standard DCF (75 mg/m2 docetaxel, 75 mg/m2 cisplatin and 750 mg/m2 fluorouracil IV over 5 days with granulocyte colony–stimulating factor; every 3 weeks).

The researchers included an early stopping rule for toxicity, defined as a grade 3 to grade 4 adverse event rate greater than 70% in the first 3 months.

Fifty-four percent of patients assigned modified DCF experienced grade 3 to grade 4 toxicities within the first 3 months, with a 22% hospitalization rate. The overall incidence of grade 3 to grade 4 toxicity in this cohort during the course of the study was 76%.

The researchers closed the DCF arm early due to severe toxicity. Seventy-one percent of patients experienced grade 3 to grade 4 adverse events in the first 3 months, with a 52% hospitalization rate. The overall incidence of toxicity in this cohort was 90%.

The most prevalent grade 3 to grade 4 toxicities in the modified DCF arm included neutropenia (56%), febrile neutropenia (9%) and fatigue (11%). Frequent grade 3 to grade 4 toxicities in the DCF arm included neutropenia without fever (45%), febrile neutropenia (16%) and gastrointestinal toxicity (58%). Both arms had a 20% rate of grade 3 to grade 4 thromboembolism.

Patients in the modified DCF arm achieved a median 6-month PFS rate of 63% (95% CI, 48-75), compared with 53% (95% CI, 34-69) in the standard DCF arm. Further, modified DCF appeared associated with improved OS (18.8 months vs. 12.6 months; P = .007).

The researchers acknowledged limitations of their study, including the smaller sample size in the standard DCF arm. Further, they acknowledged the potential for selection bias due to the longer accrual period, as well as the younger patient population.

“Based on comparable efficacy with reduced toxicity, we suggest the modified DCF regimen as a potential new three-drug standard chemotherapy option for patients with advanced gastric adenocarcinoma,” Shah and colleagues concluded. “Whereas parent DCF is associated with significant toxicity, with a high risk for patient hospitalization because of serious adverse events, even when supported by growth factors, modified DCF is better tolerated with similar efficacy.”

This article first appeared on Healio.com/HemOnc Today