Oral capecitabine/oxaliplatin/epirubicin is comparable to the intravenous option of 5-fluorouracil/cisplatin/epirubicin for untreated, advanced esophagogastric cancer, according to an article in the January 3 issue of New England Journal of Medicine.

The Phase III REAL 2 study was conducted in 1002 patients with advanced esophagogastric cancer patients from 61 centers, mainly in the United Kingdom. The study aimed to establish the potential use of capecitabine and oxaliplatin in previously untreated patients, and the primary endpoint was non-inferiority in overall survival in patients who received capecitabine (Xeloda, X) compared with those who received fluorouracil (F) and for those who took oxaliplatin (O) compared with cisplatin (C). All patients received epirubicin (E).

Patients were randomized to one of four regimens: ECF, EOF, ECX or EOX.
The primary comparison was overall survival between the capecitabine and 5-FU containing arms (ECX + EOX versus ECF + EOF) and the oxaliplatin and cisplatin containing arms (EOF + EOX versus ECF + ECX). An additional comparison was survival between all four regimens.

Study participants were limited to patients aged 18 years and older who had a histologically proven adenocarcinoma, squamous-cell carcinoma or undifferentiated carcinoma of the esophagus, gastroesophageal junction, or stomach that was locally advanced (inoperable) or metastatic.

Patients received eight three-week cycles of one of the four triplet treatment regimens. On day one, every patient received an intravenous bolus of epirubicin (50 mg/m²); cisplatin (60 mg/m²) was given intravenously with hydration in the ECF and ECX groups, and oxaliplatin (130 mg/m²) was administered intravenously during a two-hour period in the EOF and EOX groups. Fluorouracil (200 mg/m²) and twice-daily capecitabine (625 mg/m²) were given throughout the treatment in the respective patient groups.

Median survival times in the ECF, ECX, EOF and EOX groups were 9.9 months, 9.9 months, 9.3 months, and 11.2 months, respectively; one-year survival rates were 37.7 percent, 40.8 percent, 40.4 percent and 46.8 percent, respectively.

In a secondary analysis, overall survival was statistically significantly longer with EOX than with ECF, with a hazard ratio of 0.80 in the EOX group. Progression-free survival and response rates were higher for capecitabine-treated patients than those treated with 5-FU, but those differences were not statistically different.

Adverse events between capecitabine and fluorouracil appeared similar. As compared with cisplatin, oxaliplatin was associated with lower incidences of grade 3 or 4 neutropenia, alopecia, renal toxicity and thromboembolism, but with slightly higher incidences of grade 3 or 4 diarrhea and neuropathy.

In the study, median survival time was longer and one-year survival was higher among patients taking the oral triple combination compared with the standard infusion regimen.

Gastric and esophageal cancers are the second and sixth most common causes of cancer-related deaths worldwide, respectively, according to global cancer statistics published in the peer-reviewed journal of the American Cancer Society, CA: A Cancer Journal for Clinicians.

"Our research suggests that oral capecitabine and oxaliplatin can provide patients with a valuable option over the standard regimen of infused fluorouracil and cisplatin in combination with epirubicin as a first-line therapy for esophagogastric cancer," stated lead investigator Professor David Cunningham, MD, FRCP, Head of the Gastrointestinal and Lymphoma Units of the Royal Marsden Hospital National Health Service Foundation Trust of Surrey and London.

"These results are an important advance for this hard-to-treat patient population which has no other treatment option other than a lengthy, infusion- based treatment that can be inconvenient and associated with complications."