5-(3-3-dimethyl-1-triazeno)-1-methylimidazole-4-carboxamide and Melanoma

Topics: Antineoplastic Combined Chemotherapy Protocols; Dacarbazine; Humans; Interferons; Interleukin-2; Lomustine; Melanoma; Prognosis; Skin Neoplasms; Tamoxifen

A group of 668 stage II melanoma patients was entered into a randomized prospective study aimed at evaluating the efficacy of adjuvant BCG, 5-(dimethyltriazeno)imidazole-4-carboxamide (DTIC), or a combination of the two, given immediately after radical lymph node dissection. Of these, 176 patients received BCG and 164 BCG plus DTIC. These 340 patients had histologically proven metastatic nodes and 156 had a negative skin reactivity to BCG at the beginning of treatment. The distribution of known prognostic factors (sex, age, number of positive nodes, extracapsular invasion) was balanced in the groups of patients either with initially negative or with positive skin reactivity. All patients who were initially non-reactive to BCG developed skin reactivity after 6.7 +/- 9 BCG vaccinations. Disease-free and overall survival of patients receiving BCG or BCG + DTIC with an initially negative skin reactivity to BCG was significantly (P = 7 x 10(-3) better than that observed in patients with an initial positive skin reactivity. This finding was still evident after adjustment for other known prognostic criteria (P = 0.02). It seems likely that the initial BCG skin reactivity as such marks the prognosis; however, some therapeutic effect of BCG treatment in patients having initially no skin reactivity to BCG, can not be ruled out.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; BCG Vaccine; Dacarbazine; Female; Humans; Male; Melanoma; Middle Aged; Neoplasm Staging; Prospective Studies; Random Allocation; Risk Factors; Skin Tests

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Combined Modality Therapy; Cysteinyldopa; Dacarbazine; Dihydroxyphenylalanine; Female; Humans; Immunotherapy; Male; Melanoma; Middle Aged; Nimustine; Nitrosourea Compounds; Prognosis; Vincristine

The treatment of mice bearing i.m. B16 melanoma with equitoxic dosages of the clinically used 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) and of its benzenoid water-soluble analogue p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK) prior to surgical tumor removal results in a remarkable proportion of cures, even when the treatment is started on already palpable tumors for which surgery alone is ineffective. The survival time of mice which are not cured is also significantly increased with DM-COOK. At the same time, DM-COOK does not affect artificial metastases or spontaneous metastases in mice undergoing surgery and treated with DM-COOK postoperatively. Inhibition of i.m. tumor growth in surgical experiments, and of s.c. tumors in mice not treated with surgery, is significant, although not as pronounced as is necessary to obtain significant prolongation of the life span of the host; the survival time of mice with s.c. tumors treated with both drugs is indeed not significantly increased. DM-COOK thus appears to exert selective antimetastatic effects, unrelated to cytotoxicity for tumor cells, against B16 melanoma in addition to those reported for Lewis lung carcinoma and M5 ovarian reticular cell sarcoma; its therapeutic usefulness is evidenced in adjuvant surgical experiments. DM-COOK, unlike DTIC, is devoid of hematological toxicity for the host. Since, in leukemic mice, it is at least as active as DTIC in increasing the life span of the treated animals, it appears to be an advantageous substitute for DTIC that could undergo preliminary clinical trial.

Topics: Animals; Antineoplastic Agents; Combined Modality Therapy; Dacarbazine; Melanoma; Mice; Mice, Inbred Strains; Triazenes