Keeping Advanced Cancer from Advancing

Colorectal cancer with liver metastases responded to perioperative FOLFOX4

(RxWiki News) Advanced colorectal cancer can metastasize (spread) to the liver. These new tumors can be surgically removed in some patients. A follow-up study analyzed whether chemotherapy helped these patients live longer.

Compared to surgery alone, giving chemotherapy to colorectal cancer patients whose liver metastases had been removed did not prolong life, according to the long-term results of a phase III trial.

However, the study also found that chemotherapy given before and after surgery did extend progression-free survival — the time during which the disease does not worsen.

"Find out what each of your cancer therapies is designed to do."

This new study, led by Bernard Nordlinger, MD, of the Centre Hospitalier Universitaire Ambroise Paré, Assistance Publique–Hôpitaux de Paris, Université de Versailles, Boulogne- Billancourt, France, was a long-term follow-up to the European Organization for Research and Treatment of Cancer (EORTC) trial 40983.

Timothy J. Yeatman, MD, director of the Gibbs Cancer Center and president of the Gibbs Research Institute in Spartanburg, SC, told dailyRx News, "While liver resection [surgical removal] can result in cures in 20-50 percent of patients, the remaining patients will still suffer a recurrence, with many occurring in the residual liver, begging the question as to whether further therapy might prevent recurrences."
Dr. Yeatman continued, "Post-operative adjuvant therapy has been shown to have marginal benefit in previous studies. Peri-operative chemotherapy given before and after surgery has been also proposed as a means to reduce recurrence of disease in the liver following curative hepatic resection for colorectal liver metastases."

The original trial involved 40,983 colorectal cancer patients with liver metastasis that was surgically removed. These patients were recruited from 78 hospitals throughout Europe, Australia and Hong Kong.

Previously reported results from this trial showed that 35.4 percent of patients who received perioperative chemotherapy were alive and progression-free at three years, compared to 28.1 percent of patients who had surgery only.

For the follow-up conducted between 2000 and 2004, 364 patients were randomly assigned to receive either surgery alone or FOLFOX4 chemotherapy before and after surgery.

FOLFOX4 is a combination of several medications: folinic acid (brand name Wellcovorin), fluorouracil (Adrucil, Efudex, Fluoroplex) and oxaliplatin (Eloxatin).

Perioperative FOLFOX4 consisted of six 14-day cycles.

After a median of 8.5 years of follow-up, the study found the following:

  • 59 percent of patients in the chemotherapy group had died, compared to 63 percent of patients in the surgery group.
  • Median overall survival (death from any cause) was 61.3 months among patients who received chemotherapy and 54.3 months among patients who had surgery only.
  • Median five-year overall survival was 51.2 percent among the chemotherapy patients and 47.8 percent in the surgery group.
  • Two patients in the chemotherapy group and three patients in the surgery-only group died of surgery complications, and one patient in the chemotherapy group died possibly as a result of treatment toxicity.

"We found no difference in overall survival with the addition of perioperative chemotherapy with FOLFOX4 compared with surgery alone for patients with resectable [capable of surgical removal] liver metastases from colorectal cancer,” the researchers wrote, “However, the previously observed benefit in [progression-free survival] means that perioperative chemotherapy with FOLFOX4 should remain the reference treatment for this population of patients.”

According to Dr. Yeatman, "The current study, while supporting a benefit in [progression-free survival], failed to show overall survival benefit. The study, however, was not actually properly powered to predict overall survival. On the other hand, there was a 4.1 percent absolute survival benefit at 5 years which is similar to other adjuvant colon cancer trials. Thus, while there may be a marginal benefit to post-operative adjuvant therapy, the jury is thus still out as to the value for neo-adjuvant pre-operative chemotherapy or peri-operative chemotherapy in patients with resectable liver-metastatic disease," Dr. Yeatman said.

This study was published in the November issue of The Lancet Oncology.

Research funding came from the Norwegian and Swedish Cancer Societies, Cancer Research UK, Ligue Nationale Contre Cancer, the US National Cancer Institute and Sanofi-Aventis.

A number of the authors reported financial ties to various pharmaceutical companies.

Review Date: 
November 7, 2013