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Preoperative Oral Capecitabine Chemotherapy Is Equivalent to Infusional 5-FU for Rectal Cancer

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Key Points

  • Combining preoperative radiation with oral capecitabine or intravenous fluorouracil resulted in similar outcomes in local-regional control, disease-free survival, and overall survival.
  • The addition of oxaliplatin to either regimen did not provide benefit and resulted in increased toxicity.

New findings from a four-arm phase III clinical trial in patients with stage II or stage III rectal cancer indicate that combining preoperative radiation with either capecitabine or fluorouracil (5-FU) results in equivalent outcomes. This study provides strong clinical evidence that using either 5-FU or capecitabine is acceptable in this setting. The researchers also found that adding another chemotherapy drug, oxaliplatin, to either of these regimens did not provide further benefit but increased overall treatment toxicity. The findings were presented at a press conference in advance of the 2014 Gastrointestinal Cancers Symposium (Abstract 390).

“Doctors should feel reassured that they are not giving less effective therapy if they prescribe capecitabine,” said lead study author Carmen Joseph Allegra, MD, a Professor of Medicine at the University of Florida in Gainesville, Florida. “Oral capecitabine is certainly far more convenient for patients compared to infusional 5-FU. It means taking pills twice a day, rather than undergoing surgery to place an intravenous port and then wearing a pump on their belt for 5 weeks.”

Early-stage rectal cancer is potentially curable with a combination of preoperative chemotherapy, radiation therapy, surgery, and postoperative chemotherapy. Patients with operable stage II or stage III rectal cancer typically undergo chemotherapy and radiation therapy before surgery to shrink the tumor. Certain chemotherapy drugs, including 5-FU, capecitabine, and oxaliplatin, act as radiosensitizers—they make the tumors more vulnerable to radiation—but only 5-FU is currently supported by randomized clinical trials data as a radiosensitizer in the preoperative treatment of rectal cancer. Although there hasn’t been any definitive data to support the use of capecitabine in this setting, many doctors suspected it would work as it is effective as an adjuvant treatment for metastatic colorectal cancers and in the adjuvant colon setting.

Study Details

In this four-arm clinical trial, 1,608 patients were randomly assigned to receive 5 weeks of radiation therapy plus 5-FU (arm 1, 477 patients); 5-FU and oxaliplatin (arm 2, 329 patients); capecitabine (arm 3, 472 patients); or capecitabine and oxaliplatin (arm 4, 330 patients). Patients received one of these treatments for 5 weeks and about 1 month later underwent surgery to remove the tumor.

There were no significant differences between treatment arms in terms of local-regional control, disease-free survival, and overall survival. The 3-year local-regional control rates ranged from 87.4% to 88.2%. In cases where surgeons were able to completely remove the tumor (about 95% of patients) and no traces of microscopic disease were detected, 2% to 4% of stage II patients and 4% to 11% of stage III patients had a local recurrence within 3 years after undergoing surgery. And in each of the treatment arms, about 80% of patients were still alive 5 years after surgery.

Infusional 5-FU and capecitabine had similar side effects. Patients who also received oxaliplatin, however, experienced significantly more diarrhea and fatigue.

Dr. Allegra commented that although capecitabine is more expensive than 5-FU, one has to take into account that the overall cost differential for the two therapies also depends on the cost of placing and maintaining the port and pump for 5-FU infusion.

Study author Norman Wolmark, MD, reported a consultant or advisory role with Sanofi.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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