Part II: Walter Hubert Lecture Chemotherapy of Upper Gastrointestinal Carcinoma

In the Western world, carcinoma of the pancreas has waxed as gastric cancer has waned, but both remain as major causes of cancer mortality. Carcinoma of the stomach dominates the cancer incidence of Asia and the Soviet Union. Cancers of the liver and oesophagus ravage the continent of Africa in almost epidemic proportions. In spite of the great human need which this problem presents, there are few areas where the inadequacies of modern medicine are so apparent as in the management of upper gastrointestinal cancer. With all the sophistication of our diagnostic approaches, and with the ingenuity and heroism of the surgical attack, end-result statistics show that over 95% of patients found to have cancer of the oesophagus, liver, biliary tract, or pancreas will die of their disease, as will almost 90% of patients with gastric cancer. These grim statistics have changed little if at all over the past 30 years. Until methods can be evolved for either prevention or for practical detection of upper gastrointestinal carcinoma in the asymptomatic state, we must deal with the problem as the patient presents it to us, and clearly this is not at a stage amenable to surgical cure. There would not seem to be a realistic hope that advances in surgical technique per se can subsequently change these statistics. The results of surgery essentially plateaued a quarter of a century ago. Any progress, it would seem, must be derived from nonsurgical approaches. Among these, radiation therapy is hampered by its regional restriction and by lack of specificity. Immu-notherapy has, as yet, no track record and may be largely an illusion. In spite of all its limitations, the most tangible hope in the foreseeable future would seem to rest with chemotherapy. Chemotherapy of gastrointestinal carci-noma had its beginnings with the development in clinical application of 5-fluorouracil (5-FU) some 18 years ago. Early reports of the therapeutic effectiveness of this and other agents presented the reader with such a confusing labyrinth of claims and counter-claims that an aura of witchcraft hovered over those engaged in this field. New drugs or methods were extravagantly praised by one investigating group only to be damned by another. Objective response rates with 5-FU therapy of large bowel cancer, for example, were reported over the astounding range of 8 to 85%, even though all investigators were treating the same neoplasm with the same drug by the same dosage schedule …