Neoadjuvant Chemo Ups Survival in Esophageal Cancer

HAMBURG, Germany—Barely one fifth of patients who undergo surgery for esophageal cancer are alive 2 years later, and studies exploring the possible benefits of preoperative chemotherapy and radiotherapy have yielded equivocal results at best.

Solid evidence that neoadjuvant chemotherapy can improve survival without heightening the risk of postoperative complications has now come from a randomized trial performed by the UK Medical Research Council (MRC) Upper Gastrointestinal Tract Cancer Group and reported at the 25th Congress of the European Society of Medical Oncology.

Over a 6-year period, the MRC investigators recruited 802 patients with resectable esophageal cancer, no indications for urgent resection, and sufficient renal function to take cisplatin (Platinol). Three quarters were male, and two thirds had adenocarcinoma of the lower third of the esophagus. They were randomly assigned to chemotherapy followed by surgery or to surgery alone.

The chemotherapy regimen consisted of two courses, given 3 weeks apart, of cisplatin 80 mg/m² administered as a 4-hour infusion on day 1, plus a 4-day infusion of 5-fluorouracil (5-FU) 1 g/m²/d.

Fully 85% of patients who received preoperative chemotherapy were able to undergo complete resection, compared with 72% of control patients, reported Peter Clark, MD, of Liverpool, UK. Importantly, Dr. Clark pointed out, the frequencies of perioperative death and postoperative complications were virtually identical in both treatment arms, confirming the safety of neoadjuvant chemotherapy in this relatively fit patient population.

“There was a significant survival benefit for those patients who had chemotherapy prior to surgery,” Dr. Clark said. “At 2 years, your chance of being alive with just surgery is 34%, but rises to 43% if you had chemotherapy prior to the surgery.” Chemotherapy increased median survival from 13.5 months to 17.5 months. He stressed that this advantage was independent of tumor histology.

Short Interval

Commenting on the MRC trial, Jean-François Bosset, MD, of CHU Besancon (France), maintained that the relatively short 63-day median interval between randomization and surgery for patients assigned to chemotherapy was a key element accounting for the successful outcome in this trial.

He suggested that a longer delay, such as the 93-day interval reported in the US Intergroup study, might have been detrimental for those patients who did not respond to chemotherapy, permitting accelerated growth of chemotherapy-resistant cancer cells.

“My opinion is that two moderate-dose courses of cisplatin/5-FU chemotherapy should now be considered in patients with resectable squamous cell carcinoma and adenocarcinoma of the esophagus,” Dr. Bosset said.