Adjuvant FOLFOX Improves DFS in Rectal Cancer Patients

Treatment with oxaliplatin-containing FOLFOX significantly improved the 3-year disease-free survival of select patients with curatively resected rectal cancer compared with treatment with 5-fluorouracil (FU)/leucovorin.

Tae Won Kim, MD, of the department of oncology at Asan Medical Center, University of Ulsan College of Medicine in South Korea, presented the results (abstract 3502) of the phase II ADORE study at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 30–June 3 in Chicago.

“The ADORE study demonstrated that adjuvant FOLFOX improves 3-year disease-free survival compared with 5-FU/leucovorin in patients with pathologic stage II or III rectal cancer after fluoropyrimidine-based preoperative chemoradiotherapy,” Kim said.

The study included 321 patients with curatively resected rectal cancer who were postoperative pathologic stage II or III after preoperative chemotherapy with fluoropyrimidine alone. No prior oxaliplatin-based therapy was permitted.

The patients were randomly assigned to chemotherapy with 5-FU/leucovorin (n = 161) or FOLFOX (n = 160). About 95% of patients on both arms of the trial completed the planned cycles of treatment. Treatment was delayed at any cycle in 59% of patients assigned FOLFOX and 38% of patients in the 5-FU/leucovorin arm. The median follow-up was 38.2 months.

Thirty-nine disease-free survival events occurred in the FOLFOX arm compared with 53 in the 5-FU/leucovorin arm. This translated into a 3-year disease-free survival rate of 71.6% for FOLFOX compared with 62.9% for 5-FU/leucovorin (hazard ratio [HR] = 0.630; P = .032).

Isolating the results to those patients with stage III disease, the 3-year disease-free survival was 66.6% for patients assigned FOLFOX and 57.3% for patients assigned 5-FU/leucovorin (HR = 0.602; P = .04). There was no statistically significant difference in disease-free survival between the arms for patients with stage II disease. However, Kim noted that the stage II population was less than 40% of the patients included in the study.

Multivariable analysis for 3-year disease-free survival showed that the study treatment remained a significant prognostic factor, with an HR of 0.554.

“There was higher incidence of neutropenia and thrombocytopenia of all grades in the FOLFOX treatment arm,” Kim said. “In terms of grade 3 and 4 hematologic toxicity, there was no difference between the two groups.”

Fatigue and nausea were more frequently observed in the FOLFOX arm, but there was no difference in the occurrence of nonhematologic grade 3 or 4 adverse events between the two treatment arms.

The study discussant, Carmen Joseph Allegra, MD, of the division of hematology and oncology at the University of Florida, said that oxaliplatin adds benefit to fluoropyrimidine-based adjuvant rectal therapy for selected patients.

“This is supported by extrapolation from the colon adjuvant data, which in turn is supported by the genetic similarities reported in the Cancer Genome Atlas,” Allegra said. “While many of us already use oxaliplatin in this setting based on the colon data, today’s abstract provided the first direct evidence for benefit associated with the use of oxaliplatin in the rectal adjuvant setting and it further supports its use in clinical practice.”