Chemotherapy of advanced measurable colon and rectal carcinoma with oral 5‐fluorouracil, alone or in combination with cyclophosphamide or 6‐thioguanine, with intravenous 5‐fluorouracil or beta‐2′‐deoxythioguanosine or with oral 3(4‐methyl‐cyclohexyl)‐1(2‐chlorethyl)‐1‐nitrosourea. A phase II‐III study of the eastern cooperative oncology group (EST 4273)

In a randomized multi‐institutional trial of the Eastern Cooperative Oncology Group, 316 patients with advanced measurable colorectal adenocarcinoma were treated with a weekly schedule of 5‐fluorouracil given orally and intravenously with oral 5‐fluorouracil in combination with cyclophosphamide or 6‐thioguanine, or with oral Methyl CCNU administered once every eight weeks. On failure or progression, 133 protocol patients crossed‐over to a secondary therapy, while 116 other patients previously treated with 5‐fluorouracil off protocol were randomized to treatment with Methyl CCNU or B‐2′‐deoxythio‐guanosine. Response rates among patients who had received no prior chemotherapy were 18% to oral 5‐FU, 15% to intravenous 5‐FU and to MeCCNU, 12% to 5‐FU and 6‐thioguanine and 5% to cyclophosphamide and 5‐FU, with little activity (3% response rate) in crossover or previously treated patients. Treatment with 5‐FU, particularly oral 5‐FU was associated with the least drug‐related toxicity. Hematologic toxicity was greatest with Methyl CCNU, but was no more frequent in previously treated than in untreated patients. A tendency toward cumulative bone marrow depression was noted. 5‐FU was effective only in ambulatory patients, whereas responses among non‐ambulatory patients were seen only in the group treated with Methyl‐CCNU. Cancer 42:2538–2545, 1978.