_40565055_ulcer203 Stomach and gullet tumours are the third most common cause of cancer death in Scotland.  Men over 40 are the group most likely to have the disease.  Despite some increase in survival rates, only 40% of patients survive one year after diagnosis.

A group of UK researchers reported results from the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial concluded that adding a regimen of chemotherapy before and after surgery for localized gastric cancer significantly improved survival compared with surgery alone, in the July 6 issue of the New England Journal of Medicine.

This trial convincingly demonstrated a benefit from perioperative chemotherapy added to surgery and offers a new option for the treatment of localized, resectable gastric cancer. The trial was well designed and well executed and patients can have confidence in the solid evidence.

Significantly Improved Survival

The MAGIC trial, headed by David Cunningham, MD, from the Royal Marsden Hospital, London, United Kingdom, was conducted in more than 500 patients with resectable adenocarcinoma of the stomach, oesophageal junction, or lower oesophagus. Patients were randomised to treatment with surgery alone or to surgery combined with perioperative chemotherapy. After a median follow-up of 4 years, 170 of 253 patients in the surgery group had died, compared with 149 of 250 patients treated with surgery and chemotherapy.
The 5-year survival was 36% in the group that received chemotherapy compared with 23% in the group treated with surgery alone, an improvement of 13%, which corresponds to a 25% reduction in the risk of death, according to the researchers.

Chemotherapy Regimen May Be Altered

The MAGIC trial used a chemotherapy regimen consisting of epirubicin, cisplatin, and fluorouracil (ECF), administered for 3 cycles preoperatively and 3 cycles postoperatively. The cost of epirubicin used in the trial was reimbursed by Pharmacia/Pfizer, but otherwise the trial was supported by the UK Medical Research Council.

This ECF regimen was developed during the late 1980s, and there are now newer and less complex regimens available. Some are currently being tested in this patient population — for instance, capecitabine in place of fluorouracil and oxaliplatin in place of cisplatin.

Irrespective of the details of the chemotherapy regimen, the larger question was whether perioperative chemotherapy is the best way to improve the cure rate in resectable gastric adenocarcinoma.

Part of the answer hinges on when clinicians first see the patients. It is a reasonable option for patients seen before gastrectomy, but obviously it is no longer an option for those who have already undergone surgery. Yet it is not unusual for an oncologist to see such patients only after a gastrectomy with a curative intent has already been performed.

The most important point about the Cunningham study is that it provides convincing evidence to clinicians that the use of perioperative chemotherapy can help prevent cancer recurrence and improve overall survival. This study gives clinicians another useful alternative (along with postoperative radiation and chemotherapy) in managing patients with resectable stomach cancer.

Preoperative Chemo Appears to Shrink Tumours

The use of chemotherapy before surgery (neoadjuvant therapy) appears to have resulted in tumour shrinkage; the tumours in the combined-modality group were significantly smaller, with a median maximal diameter of 3 cm compared with 5 cm in the other group (P = .001).

The results of this trial may lead to a change in clinical practice in some centres, particularly in the United Kingdom and Europe, however, this will be influenced by factors such as local referral patterns and in particular the time at which the oncologist first sees the patient.

Source: New England Journal Medicine 2006;355:11-20, 76-77