HAMBURG, GermanyBarely 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
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
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.