A clinical trial of procarbazine plus vincristine plus bis-chloroethyl-nitrosourea plus imidazole carboxamide dimethyl triazeno in metastatic malignant melanoma.

Only a limited percentage of patients with metastatic malignant melanoma respond to single-agent chemotherapy. Vincristine, procarbazine, imidazole carboxamide dimethyl triazeno (DTIC) and bis-chloroethyl-nitrosourea (BCNU) have been used as single agents by various investigators. A response rate of +/- 20% was seen with vincristine (1-3) and BCNU (3, 4), and a response rate of 20-30% has been observed with DTIC (3, 5-8) and procarbazine (3, 9, 10). Newer agents such as triazeno imidazole carboxamide mustard (TIC mustard) (11), chloroethyl cyclohexyl nitrosourea (CCNU) (12), and chloroethyl methylcyclohexyl nitrosourea (methyl-CCNU) (13) have not so far proved superior. During the last years various drug combinations have been tried in an effort to improve the results of treatment in patients with metastatic malignant melanoma. In 1959 Moon reported objective response in 9 out of 20 patients who received a minimum of two courses of a combination of BCNU and vincristine (14). In a randomized trial performed by Acute Leukemia Group B (15), only 24% responded to this combination as compared to 32% and 29% for two different DTIC schedules. There were 120 patients who entered onto this protocol. A combination of DTIC plus cyclophosphamide plus vincristine was reported to give a 25% response (16). Workers at the Mayo Clinic reported objective response in 4 out of 18 patients treated with a combination of DTIC plus vincristine as compared to 1 out of 19 using CCNU (12). Costanza and co-workers (Eastern Co-Operative Oncology Group study) reported that 12 out of 61 patients responded to treatment with DTIC plus BCNU as compared to 9 out of 51 on DTIC alone (17); while Cohen (18) and co-workers reported that 10 out of 16 patients treated with the triple combination of vincristine plus BCNU plus DTIC showed significant response and concluded that this combined approach in the treatment of disseminated malignant melanoma warranted further study. Preliminary analysis of an Eastern Co-Operative Oncology Group protocol showed no statistical advantage of DTIC plus methyl-CCNU over each drug on its own (19). The present study was undertaken to investigate the possible advantage of combining DTIC plus vincristine plus BCNU plus procarbazine in courses of treatment. All of these agents are of some value on their own and all four have possible different mechanisms of action.     

A random phase II study of mitoxantrone and cisplatin in patients with hepatocellular carcinoma. An ECOG study

Of 86 patients entered in an Eastern Cooperative Oncology Group (ECOG) random Phase II study of mitoxantrone (DHAD) and cisplatin (DDP) in primary liver cancer, 69 were eligible. Nine of the 13 ineligible patients were excluded after a pathology review. Sixty-one percent of the patients were North American, and 39% were South African. The most common severe or the worst toxicity on DHAD was hematologic; and to DDP, hematologic and vomiting. Of the 69 eligible patients, 21 experienced severe, life-threatening or fatal toxic reactions. Two patients treated with DDP had partial responses. With a 95% confidence interval, the true response rate to DHAD was less than 8%, and to DDP, less than 17%. The median survival time was 14 weeks on both drugs. Assuming a proportional hazards model, factors that are significantly associated with survival are patient performance status, the presence of the symptoms, raised bilirubin and hepatomegaly, and clinical evidence of cirrhosis. Any differences between survival rates for South African and North American patients were largely explainable by these factors.     

Intranasal buserelin in the treatment of advanced prostatic cancer: a phase II trial

Thirty-five patients with advanced prostatic cancer were entered in a trial of nasally administered gonadotropin-releasing hormone analogue agonist (GnRHA) buserelin. Four patients were unevaluable for response and toxicity. Twenty-five patients responded to treatment, two with complete remissions, 12 with partial remissions, and 11 who improved. The median baseline value for testosterone was 14.4 nmol/L. After 1 week of treatment, the median value was 10.8 nmol/L, while after 1 month the median value had decreased to 1.1 nmol/L (normal, 10.0 to 34.7). It is concluded that intranasal buserelin is an effective, simple, and safe method to achieve androgen deprivation in the treatment of advanced prostate cancer and is an alternative to orchiectomy and more acceptable than daily subcutaneous injections.     

Sister chromatid exchanges in lymphocyte cultures of patients previously treated with dibromodulcitol

Acute non-lymphatic leukaemia and myelodysplasia occur in a larger percentage of patients treated with dibromodulcitol (DBD) than in patients treated with other cytostatics. Sister chromatid exchanges (SCE) in the lymphocytes in peripheral blood as well as other haematological parameters were measured in women with breast cancer to investigate whether women who had previously been treated with DBD as a part of their treatment regime had an increased frequency of SCE or another haematological abnormality attributable to DBD. SCE levels were elevated in women treated with DBD as well as in those treated with other cytostatics compared to the untreated control group. All other haematological parameters were normal. There was no significant difference in the number of SCEs between the patients who received DBD and those treated with other cytostatics. The increased frequencies of SCE in the treated patients are attributable to various cytostatic agents, and there is no significant permanent increase in the frequency of SCE after exposure to DBD.     

Zur Kenntniss der Kiefercysten

Ohne ZusammenfassungHierzu Taf. VIII. Fig. 5.     

Normalization of skin appearance in a patient with scleromyxoedema after intensive chemotherapy for Hodgkin's disease

A patient with scleromyxoedema was treated for 6 years with cytostatic drugs. During this time the skin lesions followed a fluctuating but progressive course. After 6 years she developed Hodgkin's lymphoma of the mixed cellularity type. Intensive cytostatic treatment given for Hodgkin's disease resulted in virtually complete disappearance of the scleromyxoedema lesions. The development of Hodgkin's disease is considered fortuitous and not due to the previous cytostatic drugs.     

Metastatic breast cancer--age has a significant effect on survival

The data on 217 elderly (aged greater than or equal to 65 years) and 209 middle-aged postmenopausal patients with metastatic breast cancer treated in the Department of Medical Oncology, University of Pretoria, from 1976 to 1985 were analysed to determine the effect of age on survival. When considered as a group, the elderly have a more favourable prognosis (median survival 20.3 months) than the middle-aged (median survival 15.54 months) (P = 0.0457). Multivariate age subset analysis (taking into account all other major prognostic factors) reveal a distinct bimodal pattern. The median survival of patients aged 45-54 years is 21.2 months and decreases to 16.2 months for patients aged 55-64 years (P = 0.08; Cox model). The median survival improves again to 24.6 months for patients aged 64-74 years (P = 0.0001; Cox model), followed by an apparent but non-significant decrease to 17.1 months in the very old (aged 75-84 years) (P = 0.52; Cox model). The more favourable prognosis in the elderly dictates effective non-toxic treatment.