SAN FRANCISCO – Oral capecitabine is as effective as infused 5-fluorouracil when given as part of neoadjuvant therapy for rectal cancer, new data show. Adding oxaliplatin to either regimen increases toxicity and does not improve efficacy.
These were among the mature results of the National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol R-04 trial, being reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.
In the trial, 1,608 patients with resectable stage II or III rectal cancer received neoadjuvant chemoradiotherapy consisting of radiation plus either capecitabine or fluorouracil, each with or without oxaliplatin.
The 3-year rate of locoregional control was high overall, at almost 90%, and statistically indistinguishable between patients who received capecitabine and patients who received 5-fluorouracil (5-FU), lead study author Dr. Carmen Joseph Allegra, a professor of medicine at the University of Florida in Gainesville reported in a press briefing.
Dr. Carmen J. Allegra
"Capecitabine with preop radiation therapy achieved rates similar to continuous infusion 5-FU for the primary endpoint of locoregional failure, as well as for pathologic complete response rate and longer-term outcomes such as disease-free survival and overall survival," Dr. Allegra commented. "This study establishes capecitabine as a standard of care in the preop rectal setting."
"Oxaliplatin did not improve outcomes but added significant toxicity, primarily in the form of diarrhea, and is therefore not indicated in combination with radiation therapy in the preop rectal therapy setting," he added.
Capecitabine has advantages over 5-FU in terms of convenience and avoidance of the need to place central venous catheters and use infusion pumps. Although capecitabine is more expensive in terms of simple drug cost, 5-FU carries the additional costs of ports and infusions.
"This study in over 1,600 patients definitively demonstrates that patients can be treated with oral capecitabine instead of continuous infusion 5-FU, giving our patients a more convenient treatment option. The study also adds to data from prior trials concluding that oxaliplatin does not improve tumor response in this setting," commented press briefing moderator Dr. Smitha Krishnamurthi of Case Western Reserve University in Cleveland.
For the R-04 trial, patients were randomly assigned to receive 5 weeks of radiation therapy. They also received either 5-FU alone; 5-FU with oxaliplatin; capecitabine alone; or capecitabine with oxaliplatin. About a month later, they underwent surgery.
Capecitabine (Xeloda) is approved by the Food and Drug Administration for the treatment of breast and colorectal cancers. Fluorouracil (Adrucil) is approved for the treatment of colorectal and multiple other cancers. Oxaliplatin (Eloxatin) is approved for the treatment of colorectal cancer.
Main results showed that the trial arms were statistically indistinguishable with respect to rates of locoregional control, which required that the patient undergo surgery, have an R0 (complete) resection, and not have any recurrence.
The 3-year values ranged from 87.9% to 88.8%, with no significant difference between the capecitabine and 5-FU groups, or between the oxaliplatin and no-oxaliplatin groups.
The rate of locoregional recurrence was about 4% overall, with values essentially the same across groups, reported Dr. Allegra, who disclosed no relevant conflicts of interest.
In the entire trial population, the 5-year rate of disease-free survival was about 65%, and the 5-year rate of overall survival was about 80%, also with statistically indistinguishable rates by group.
There was no evidence of a significant interaction between capecitabine/5-FU treatment and oxaliplatin treatment in any of the efficacy analyses.
Capecitabine and 5-FU were similar with respect to the rate of overall grade 3 or worse toxicity (30% and 27%) and grade 3 or 4 diarrhea (7% for each).
However, adding oxaliplatin to either regimen increased to 40%-42% the rate of overall grade 3 or worse toxicity and to 16% the rate of grade 3 or 4 diarrhea.