Recent Advances in Cytotoxic Therapy for Gastrointestinal Carcinoma: A Review

Abstract

Single-agent therapy Until recently the use of cytotoxic drug therapy in gastrointestinal cancer has been confined to the administration of single drugs to patients with advanced, incurable, disease. The results of this approach are summarized in Table I. The modest success of 5-fluorouracil, noted sooã fter its introduction 18 years ago, has tended to inhibit the evaluation of other agents, clinical resources being largely devoted to determining the optimum dose and route of administration for 5-fluorouracil. Mitomycin-C has been widely used in Japan, but there were fatalities with high doses when it was first used in the West. At lower doses it is a safe and valuable agent, but the stigma of the original toxicity has inhibited its acceptance. By the early 1970s it became clear that intermittent intravenous administration was the optimum regimen for 5-fluorouracil and nothing more could be expected from variations in the route of administration and dose schedules (Moertel 1975). Clinicians began to explore other drugs and this shift of attention corresponded with the appearance of several new compounds that were immediately assessed. This move directly from 5-fluorouracil to new agents has meant that many of the established anti-cancer drugs have been inadequately assessed in gastrointestinal cancer. The first group of new drugs to be screened were the nitrosoureas, comprising BCNU, CCNU and methyl-CCNU (Me-CCNU). The initial assessment suggested that MeCCNU and BCNU were active in stomach and large-bowel cancer. Subsequent comparative studies in large-bowel cancer showed that MeCCNU was more effective than BCNU and that, with an overall response rate of 26%, it might have an activity comparable to

Review of general surgery 1978

“…5-Fluorouracil with methyl CCNU was compared against untreated controls in patients with unresectable gastric cancer. In a total of 193 cases, no difference could be found in overall survival or quality of life between the 2 groups, although it should be noted that only 41% of the treatment group could receive the full course of both drugs The results of single agent therapy in advanced gastrointestinal cancer is not encouraging although rather better results are reported with combination chemotherapy (Priestman, 1978).…”

Colorectal Cancer: The Modern Treatment of Disseminated Disease ‐ a Review

“…This marked discrepancy between increased response rate, but failure to prolong survival, has been well recognized by Schein and Hoth (1 978), and separates colorectal cancer from most other malignancies. Furthermore, many later studies, using drug combinations similar to that of Moertel and Falkson, have failed to substantiate the initially promising results and have given response rates no greater than those for 5-FU alone (Kane et alii, 1978;Belt and Stephen, 1979;Kemeny et alii, 1979, Priestman, 1978Buroker et alii 1978a;Buroker et a h , 1978b). A further death knell to the early enthusiasm for increased response using combination chemotherapy has been the inability of Moertel to confirm his own earlier encouraging report.…”

Radiotherapy in Management of Gastrointestinal Carcinoma: A Review

“…The overall 5-year survival rate is 11% (Waterhouse 1974). These depressing figures have not altered for a number of years, despite the introduction of cytotoxic agents (Philip 1978, Priestman 1978. Recently there have been a number of reports on the value of radiotherapy used with surgery for carcinoma of the rectum.…”