SAN FRANCISCO — Patients receiving preoperative chemotherapy for rectal cancer do not have to undergo the hassle and discomfort of intravenous infusion any longer, according to the results of a major randomized trial sponsored by the National Cancer Institute.
Investigators found that in patients with stage II or III disease, outcomes and toxicity were similar with an oral drug, capecitabine, and with the current standard of care, which is continuous intravenous infusion of 5-fluorouracil (5-FU).
All patients also received concurrent radiation therapy before undergoing curative surgery.
This study "establishes capecitabine as a standard care in the preoperative rectal cancer setting," said lead investigator Carmen Joseph Allegra, MD, professor of medicine at the University of Florida in Gainesville.
He spoke at a press conference held in advance of the 2014 Gastrointestinal Cancers Symposium.
"Oral capecitabine is certainly far more convenient for patients than infusional 5-FU," Dr. Allegra said in a press statement. "It means taking pills twice a day, rather than undergoing surgery to place an intravenous port and then wearing a pump on the belt for 5 weeks."
There were no significant differences between the 2 chemotherapies in terms of local-regional control, which was the primary outcome, report Dr. Allegra and his colleagues from the National Surgical Adjuvant Breast and Bowel Project (NSABP) R-04 trial.
The 3-year local-regional event rate was similar with capecitabine and 5-FU (11.2% vs 11.8%; P = .98), as was the 3-year local-regional recurrence rate (3.6% vs 3.8%; P = .52)
Disease-free survival, overall survival, and pathologic complete response were also similar.
"This large study of more than 1600 patients definitely demonstrates that patients can be treated with capecitabine instead of continuous intravenous infusion 5-FU, giving our patients a more convenient treatment option," said Smitha S. Krishnamurthi, MD, associate professor of medicine at Case Western Reserve University in Cleveland, who moderated the press briefing during which the results were presented.
"Doctors should feel reassured that they are not giving less-effective therapy if they prescribe capecitabine," Dr. Allegra added.
The only downside to capecitabine is that it is more expensive than 5-FU, said Dr. Allegra. However, there are additional expenses with 5-FU, and the cost of placing and maintaining the infusion port and pump need to factored into the overall cost differential.
No Help From Oxaliplatin
NSABP R-04 is actually a 4-group clinical trial of 1608 patients.
In addition to randomly assigning patients to 5 weeks of 5-FU (n = 477) or capecitabine (n = 472), the investigators randomized patients to a combination of 5-FU plus oxaliplatin (n = 329) or capecitabine plus oxaliplatin (n = 330).
The 5-FU was administered at 225 mg/m² daily and the capecitabine was administered at 825 mg/m² twice daily. The oxaliplatin was administered intravenously at 50 mg/m² once a week.
Oxaliplatin was used in this study because it, like 5-FU and capecitabine, is a radiosensitizing agent and makes tumors more vulnerable to radiation.
Patients in all 4 groups received concurrent preoperative radiation therapy, which consisted of 4500 cGy delivered in 25 fractions over 5 weeks plus a boost of 540 cGy to 1080 cGy delivered in 3 to 6 daily fractions. All of the patients received the neoadjuvant treatment for 5 weeks and underwent surgery to remove the tumor about a month after the chemoradiation.
The addition of oxaliplatin did not provide any additional benefit in local-regional control. When added to either 5-FU or capecitabine, oxaliplatin provided about the same local-regional event and recurrence rates as the other 2 agents alone.
However, oxaliplatin increased overall treatment toxicity, including more grade 3/4 diarrhea (P < .0001).
Dr. Allegra and Dr. Krishnamurthi have disclosed no relevant financial relationships.
2014 Gastrointestinal Cancers Symposium (GICS): Abstract 390. Presented January 18, 2014.
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