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PubMed1980

Treatment of brain giomas with high dose of CCNU and autologous bone marrow transplantation.

Seven patients with recurrent brain gliomas were treated by a single dose of CCNU 390 mg per m2. In five cases, chemotherapy was followed by autologous bone marrow transfusion containing 1.5 to 3 X 10(8) nucleated cells, 2.8 to 18 X 10(4) clusters plus colonies and 0.4 to 5 X 10(4) colonies forming cells per kg of body weight. Two patients were not grafted. None of these patients showed a clear cut response to the treatment as judged by clinical improvement and changes of the brain CT-scan. In 3 patients blood toxicity occurred early and was severe. In 4 others, it was milder and delayed. The duration and the severity of blood toxicity were modified by bone marrow transfusion but only slightly.

Bone Marrow Transplantation↗
PubMedDate not supplied

CCNU, melphalan, methotrexate, and prednisone (CAMP) versus cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) in the treatment of advanced breast cancer in postmenopausal women.

Sixty-nine postmenopausal patients with advanced breast cancer were randomized to receive treatment with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or CCNU, melphalan, methotrexate, and prednisone (CAMP). Response rate (partial and complete remission) was significantly higher with CMF (50%) than with CAMP (20%). Hematologic toxic effects were equally pronounced with the two combinations as were the other side effects with the exception of alopecia, which occurred most frequently with CMF.

Aged↗
PubMedDate not supplied

Phase II study of vinblastine-CCNU, triazinate, and dactinomycin in advanced renal cell cancer.

A total of 133 patients with advanced or metastatic adenocarcinoma of the kidney were stratified according to performance status and time from initial diagnosis to recurrence and were then randomized to one of three different drug treatment arms or the crossover secondary treatment. The study drugs (combination vinblastine-CCNU and single-agent triazinate or dactinomycin) failed to provide any meaningful antitumor activity for these patients with advanced renal cell cancer.

Adenocarcinoma↗
PubMed1981

Hodgkin's disease in childhood: therapy results in Argentina.

From 1940 to 1977, a total of 152 children aged 15 years or less with the histologic diagnosis of Hodgkin's disease were treated in Argentina. For analysis, these patients were placed into three periods which displayed the most outstanding changes in diagnostic workup and therapy. The periods are as follows: (1) 1940 to 1966 (43 children), (2) 1967 to 1972 (35 children), and (3) 1973 to 1977 (74 children). The patients were treated with extended field radiation therapy and followed by courses of cyclophosphamide-vinblastine-procarbazine-prednisone, with CCNU added (CCVPP) or not added (CVPP) in a randomized trial. The mean age of the whole group was 7.5 years (range 2 to 15 years) and there was a predominance of males (79%). Crude 6-year survival for the three periods were as follows: 1940 to 1966, 34%; 1967 to 1972, 50%; and 1973 to 1977, 79%. We conclude that (1) survival of Hodgkin's disease of childhood has shown a rather marked improvement during the last decade and this progress is probably due to the use of combined multidrug chemotherapy administered under collaborative controlled clinical trials; (2) preliminary evaluation of the results of CVPP and CCVPP therapy shows that the latter combination (CCVPP) neither increases the percent of patients achieving complete remission nor prolongs relapse-survival in Hodgkin's disease of childhood: and (3) all stages of childhood Hodgkin's disease can be successfully managed with multidrug chemotherapy alone.

Adolescent↗
PubMedDate not supplied

Immediate versus postponed combination chemotherapy (CAMP) for unresectable non-small cell lung cancer: a randomized trial.

A randomized control trial was performed in good performance status patients with unresectable non-small cell lung cancer to test a strategy of early aggressive combination chemotherapy (CAMP [cyclophosphamide, doxorubicin, methotrexate, and procarbazine]) versus a strategy of delaying such treatment until clinical deterioration. Thirty-seven patients received immediate CAMP and 35 patients received initial low-dose single-agent CCNU (CAMP was postponed). Immediate CAMP therapy produced an objective response rate of 44% in patients with measurable lesions, and CCNU produced none. Median survival was 193 days for the immediate-CAMP group and 175 days for the postponed-CAMP group (P = 0.26). Measures of quality of life were made and no difference emerged between the two treatment strategies. This trial failed to show substantial benefit from immediate combination chemotherapy in minimally symptomatic patients with non-small cell lung cancer.

Antineoplastic Agents↗
PubMed1981

[Background and experience of adjuvant cytostatic therapy in gastrointestinal cancer (author's transl)].

Survival rates for patients with colorectal cancer have remained unchanged during the last 30 years. Every third patient with colon cancer Dukes' C and every fourth patient with rectal cancer Dukes' C survives 5 years. Of the patients who succumb to colorectal cancer, 85% will die within 3 years from diagnosis. There are many studies concerning the mechanisms of adjuvant chemotherapy. Its effectiveness has been proven in animal experiments. Micrometastases have a large growth fraction, few non-proliferative cells, and because of this, increased sensibility to cytostatics. Adjuvant chemotherapy aimed at treating occult metastases. In colorectal cancer the combination of 5-FU and Nitrosurea has been shown to have a better effect than 5-FU alone. Grage et al. have shown patients with colorectal cancer Dukes' C to have a longer tumour-free interval with adjuvant 5-FU, and this treatment gives patients with rectal cancer a prolonged survival time. In an adjuvant study, peroral 5-FU 90 days versus placebo did not show any effect. In another adjuvant study Vincristin, CCNU and 5-FU treated patients had fewer tumour recurrences than control patients. The observation time is, however, rather short. Adjuvant chemotherapy for colorectal cancer has shown promising results and it is hoped that further attempts with other forms of cancer in the gastrointestinal tract will also yield the same results.

Antineoplastic Agents↗
PubMed1981

A review of studies of the EORTC brain tumor group.

The results of three randomized trials performed by the EORTC Brain Tumor Group in patients with histologically proven brain gliomas are presented. CCNU (130 mg/m2 every 6 weeks) in combination with dexamethazone (4-20 mg daily) prolonged total survival compared to a group of patients treated only with corticosteroids. CCNU (130 mg/m2 every 6 weeks) either alone or one day after VM-26 (100 mg/m2) produced an objective remission in less than 30% of treated patients. However, the two treatment modalities did not prolong the interval between surgical removal of the tumor and relapse (recurrence). None of 12 patients with signs of brain tumor recurrence previously treated with VM-26 plus CCNU responded to procarbazine (3-week courses of 150 mg/m2/day).

Antineoplastic Agents↗
PubMed1982

Quantitative dose-response relations for the cytotoxic activity of chloroethylnitrosoureas in cell culture.

A dose-response relation for the cytotoxic activity of chloroethylnitrosourea cancer chemotherapeutic agents in cell culture has been developed. Data for the activity of 1,3-bis(2-chloroethyl)-1-nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea, and 1-(2-chloroethyl)-3-(piperidine-3,6-dion-3-yl)-1-nitrosourea against 9L rat brain tumor cells are presented. Cytotoxicity resulting from treatment schedules at different initial drug concentrations, exposure periods, and preincubation periods are correlated using a proposed dose function. Equations are presented that incorporate drug concentration, duration of exposure of cells, and the rate constant for conversion of the drug from an active intermediate into a single dose function. When compared in this way, all cell treatment schedules used were found to be equally effective in killing cells in culture. The cytotoxic activity of the four different chloroethyl-nitrosourea analogs were also found to be the same. These data demonstrate the application of quantitative dose-response relations to the activity of chloroethylnitrosoureas in cell culture and provide new insight into the mechanism of action and structure-activity relationships of these compounds.

Animals↗
PubMed1982

Experimental approach for the search of effective drug combination in cancer chemotherapy.

A comparative assay of cytostatic combinations was carried out in a number of transplantable mouse tumors: L1210, Lewis lung carcinoma, Sarcoma 180 and others. The results suggest that the combination cyclophosphamide (CPH) plus procarbazine (PROC) enhances the antitumoral activity in comparison with monochemotherapy. The combination CPH + PROC can be used as basis for the elaboration of more effective polychemotherapy schemes. Combination of CPH + PROC + Prospidine and CPH + PROC + CCNU resulted in enhancement of the treatment effect in experimental tumors.

Adenocarcinoma↗
PubMed1982

Medulloblastoma in childhood. Multidisciplinary treatment.

20 medulloblastomas in children were treated at the Neurosurgical Department of Perugia over the last 6 years. The age ranged between 1.2 and 15 years, with a mean of 8 years. The ratio between males and females was 3/1. Only three tumors were localized within one cerebellar hemisphere. A shunt was performed before the removal of the tumor in 12 cases. Radical resection was completed in 15 cases, whereas a subtotal removal was performed in the cases with involvement of the brain stem. The postoperative mortality rate was 5%. The 3-year survival rate was 40% and the 5-year 25%. The postoperative radiotherapy was given at lower doses than usually reported by other authors: this seems to reduce the neuropsychological and endocrinological sequelae. CCNU of BCNU were given after radiotherapy, but this monochemotherapy seems to be less effective than polychemotherapy with CCNU, vincristine, procarbazine and dexamethasone, used in this series when relapse occurred. Radical resection improved the prognosis. The opportunity of using different protocols for 'low risk' and for 'high risk' patients is finally discussed.

Adolescent↗
PubMed1977

Overview of four clinical studies of chemotherapy for stage III and IV non-Hodgkin's lymphomas by the Cancer and Leukemia Group B.

This paper presents an overview of four Cancer and Leukemia Group B studies in 1266 patients with stage III-IV non-Hodgkin's lymphoma. The cases were analyzed across protocols; the major prognostic determinants were prior chemotherapy, age, and histology. The four studies proved that cyclophosphamide maintenance was superior to no maintenance even after prolonged intensive induction chemotherapy. Furthermore, the reinforcement program of monthly pulse doses of vincristine and prednisone, whose value was established in the treatment of acute leukemia, led to highly significant improvement in remission duration and survival. Other facets of the chemotherapy programs are still being subjected to analysis, but this report sets out some preliminary conclusions.

Adult↗
PubMed1982

Modifications of DNA by different haloethylnitrosoureas.

The modification of DNA by the haloethylnitrosoureas is probably responsible for their antitumor activity. A current hypothesis relates this cytotoxic action to the transfer of haloethyl groups from the nitrosourea to DNA followed by a second reaction of the haloethyl group with the opposite DNA strand. However, other modifications besides interstrand cross-links are introduced into DNA, raising the question whether the choice of the particular nitrosourea could affect the distribution of DNA modifications in a way which would maximize cytotoxic activity. To investigate this point, DNA was reacted with the following compounds: N,N'-bis(2-chloroethyl)-N-nitrosourea (NSC 409962); N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea (NSC 79037); N-(2-chloroethyl N'-(2,6-dihydroxycyclohexyl)-N-nitrosourea (NsC 264395); N-(2-chloroethyl)-N-nitrosourea (NSC 47547); and N-(2-fluoroethyl(-N'-cyclohexyl-N-nitrosourea (NSC 87974). Reacted DNA was depurinated, and the distribution of guanine derivatives was obtained by high-pressure liquid chromatography. These studies have shown that the distribution of products obtained is markedly influenced by the chemical structure of the nitrosourea. Differences are noted in the relative amounts of 6- versus 7-substituted guanines, in the amount of hydroxyethylation versus haloethylation, and in the amount of diguanylethane formation. Thus, it may be possible to modulate the biological effect obtained from a nitrosourea by changing its molecular structure.

Animals↗