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Twenty-six patients with mycosis fungoides were treated topically with three nitrosourea compounds: carmustine (BCNU), lomustine (CCNU), and 1-methyl-1-nitrosourea. A high percentage experienced good to excellent results. Remissions following treatment of individual lesions varied from one month to at least three years. Remissions following total body surface treatment varied from two weeks to at least four months. Two of 13 patients treated over the entire body suffered temporary bone marrow depression, indluding one with severe pancytopenia. This toxic effect was attributed to lomustine and was not seen in patients treated with carmustine alone. Thirteen patients highly allergic to mechlorethamine hydrochloride showed no cross-sensitivity to nitrosourea compounds. A primary irritant dermatitis occurred in about one half of the patients and telangiectasia in two. Two patients developed hypersensitivity to nitrosourea compounds. Carmustine is the preferred nitrosourea compound for topical therapy of mycosis fungoides.

In March of 1972, the Southwest Oncology Group initiated a Phase II study, No. 7200, utilizing methyl-CCNU in the treatment of patients with solid tumors and lymphomas. Initially, they received 200 mg/m2 orally as a single dose every 6 weeks. The dose was subsequently reduced in poor-risk patients to 150 mg/m2. There were 69 responses noted in 675 evaluable patients (10%). The highest response rates were noted in patients with Hodgkin's disease (13/31, 35%), malignant gliomas of the brain (8/29, 28%), anaplastic carcinomas of the lung (5/20, 25%), and squamous cell carcinomas of the head and neck (5/29, 17%). Squamous cell tumors appeared to be more responsive than adenocarcinomas (15% vs. 5%, respectively). Hematologic toxicity was cumulative, and was influenced by dose and prior treatment. There appeared to be no cross-resistance in patients previously treated with alkylating agents. Methyl-CCNU is an active antineoplastic agent. Further studies are indicated in order to determine relative effectiveness.

Oral administration of N-nitrosomethylurea at maximally tolerated doses to guinea pigs on alternate days from days 34-58 of pregnancy induced prenatal toxicity, as evidenced by a high frequency of stillbirths and intrauterine growth retardation, and postnatal toxicity, as evidenced by stunting and progressive mortality. Similar administration of N-nitrosomethylurethane at maximally tolerated doses did not induce such toxic effects.

In a randomized, controlled study of 80 patients with advanced colorectal carcinoma, the combination of 5-fluorouracil (5-FU), methyl-1, 3-cis(2-chlorethyl)-1-nitrosourea, and vincristine produced an overall degree to toxicity comparable to that of 5-FU used alone. At 10 weeks, a positive objective response rate of 43.5% was observed with the three-drug combination compared to 19.5% with 5-FU alone (P less than 0.5).

The effect of N-nitrosomethylurea on the blood-glucose and the pancreatic islet light microscopic picture was studied in the Chinese hamsters, golden hamsters, guinea pigs, mice, rats and sand rats. The Chinese hamsters were most susceptible. Only in this species did a dose of 50 mg/kg body weight cause blood-glucose elevations and pancreatic islet damage. At a dose of 100 mg/kg body weight of N-nitrosomethylurea, blood-glucose elevations were recorded in the golden hamster together with damage to the islets and the exocrine pancreatic parenchyma. A toxic dose of 200 mg/kg body weight resulted in hyperglycemia and islet cell destruction in the rat and in slight alterations in the islets of mice. N-nitrosomethylurea was non-diabetogenic to guinea pigs and sand rats. The ethyl derivate of nitrosourea was less toxic and diabetogenic to the Chinese hamsters in comparison with the methyl derivate.