ABSTRACT
Therapeutic strategies for colorectal cancer have evolved over the past four decades. Early empirical approaches included the identification of drugs with single-agent activity. Two or more drugs were then combined in the hope that the multidrug regimen would be more effective than the individual agents given alone. 5-FU emerged as the most useful agent for colorectal cancer, although nitrosourea compounds and mitomycin C also had modest activity. Initial studies involving a combination of semustine, vincristine, and 5-FU seemed promising in advanced disease (with response rates of about 40%). Semustine plus 5-FU (with or without vincristine) were subsequently evaluated in the adjuvant therapy of colorectal cancer. Many years elapsed before two definitive randomized trials refuted the benefit of adding semustine to 5-FU. Because both mitomycin C and nitrosoureas have the potential for chronic hematologic, pulmonary, and renal toxicity, they are now infrequently used to treat colorectal cancer.
