[Phase II study of the water-soluble nitrosourea compound ACNU in advanced colorectal carcinomas]

In a phase-II study 46 patients with advanced colorectal cancer were treated with the new nitrosourea ACNU [1-(2-chloroethyl)-1-nitroso-3 (4-amino-2-methyl-5-pyrimidinyl)methyl-3-nitrosourea]. From 43 evaluable patients, 86% presented distant metastases and 14% an unresectable primary tumour or a recurrent tumour. 24 patients presented a colon and 19 a rectal cancer. Prior anticancer drug treatment was given to 34 patients (79%), 11 (26%) were pretreated with a nitrosourea. ACNU was administered every 4-6 weeks as a single intravenous push injection of 100 mg/m2. Most patients received 2-3 courses. From 43 evaluable patients, one patient achieved a complete and 3 a partial remission (CR + PR 9%). 5 patients reached a minimal regression (tumour regression of less than 50%) and 5 a no change for at least 2 months. The median duration (time from beginning of ACNU therapy until tumour progression) of the 14 responders was 132 days. The median survival time was significantly longer for responders in comparison to patients with progressive disease (9.8 versus 4.1 months). The dose limiting toxicity was delayed bone marrow suppression predominantly in the form of thrombocytopenia. 22/42 patients (52%) presented a thrombocytopenia of under 50.000/mm3 with a nadir after 27 days. Leucocytopenia under 2.000/mm3 were observed in 22/40 patients (30%). A fall of haemoglobin of more than 2 g/dl was seen in 71%. Nausea or vomiting over 1-2 days were found in 59% of the treatment courses. Other drug related side effects were not encountered. ACNU has a similar activity in colorectal cancer as BCNU and CCNU.(ABSTRACT TRUNCATED AT 250 WORDS)