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At least 379 records · Page 21Linked to original sources
PubMed1982

[The combination methyl-CCNU, vincristine, 5-fluorouracil and streptozotocin in the treatment of advanced colo-rectal adenocarcinoma].

Sixteen patients with advanced colo-rectal cancer were treated with the combination methyl-CCNU, vincristin, 5-fluorouracil and streptozotocin (MOF-Strepto). Seven cases were previously untreated. A partial remission was observed only in one patient (6%, confidence limits to 95%: 1-17%). Marked gastrointestinal and hematologic toxicity was registered. Based on this experience the authors are unable to confirm other pilot studies claiming major antitumor activity for MOF-Strepto in the treatment of advanced colo-rectal cancer.

Adenocarcinoma↗
PubMed1982

[Cancer chemotherapy with special reference to pharmacokinetics of nitrosoureas].

This paper provides an overview of cancer chemotherapy with special reference to the pharmacokinetics of the nitrosoureas. At physiological PH, the chloroethylnitrosoureas can be decomposed into an isocyanate and 2-chloroethyl diazene hydroxide. Therefore, it is clear that they have both alkylation and carbamoylation actions. In addition to the spontaneous chemical dissociation, the nitrosoureas can be metabolized by liver microsomal enzymes to more polar hydroxylated products, and certain nitrosoureas can be denitrosated by these enzymes to the parent urea. Since the lipid-soluble nitrosoureas and some of the water-soluble nitrosoureas such as ACNU and MCNU demonstrated to cross the blood-brain barrier, they have been used in the treatment of primary brain tumors and tumors and tumors of metastatic origin. It has been demonstrated from the results of our study and other reports that the alkylation of DNA by ACNU progresses more slowly as compared with that of other alkylating agents. This is an important finding in relation to the appearance of delayed myelosuppression of the nitrosoureas and in the design of dose schedules of these agents. The major clinical emphasis has been directed towards the more active chloroethylnitrosoureas with reduced myelosuppression, and attempts are now made for this purpose. Unfortunately, the results of phase I and II trials of the newly developed nitrosoureas suggest that these agents produce delayed and cumulative bone marrow toxicity. Antitumor activity of the nitrosoureas is frequestly observed in chronic myelocytic leukemia, malignant lymphoma, brain tumors and small cell carcinoma of the lung, and less frequently in gastrointestinal carcinoma, multiple myeloma and malignant melanoma. In order to enhance clinical effects of the nitrosoureas, further investigation of the design in therapeutic schedules on the basis of their pharmacokinetic characteristics will be needed.

Carmustine↗
PubMed1978

Differential repair of 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea-induced DNA damage in two human colon tumor cell lines.

Two human colon tumor cell lines were examined for their responses to 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea treatment when maintained as cultured cell lines and xenograft tumors in nude mice. One tumor line, HT, was resistant to 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea treatment both in tissue culture and in vivo. The other tumor line, BE, was sensitive to 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea treatment in vitro and in vivo. The DNA of tissue-cultured cells treated with 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea was examined by alkaline elution for DNA damage. 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea was found to produce DNA strand breaks and DNA cross-links in both cell types. The DNA cross-links appear to be completely repaired in the resistant HT line over the 48-hr period following drug removal, but in the sensitive BE line little or no cross-link repair was observed during this interval.

Animals↗
PubMed1984

Preliminary research on the evaluation of some prognostic factors in a randomized study of adjuvant immunochemotherapy in colorectal adenocarcinoma.

In a randomized, multicenter study, 168 evaluable patients with colorectal adenocarcinoma at B2, C1 or C2 stages of the Dukes, Astler and Coller classification, were treated after radical surgery with BCG and 5-fluorouracil alone (regimen A) or in combination with hydroxyurea, methyl-CCNU and mitomycin C (regimen B). Radiation therapy was mandatory after surgery for rectal cancer. Response to therapy was evaluated for length of disease-free interval after surgery and was analyzed in comparison to the data obtained upon entrance to the study. The results are reported as life curves of the duration of the disease-free interval for treatment in comparison to the presence or absence of various signs or symptoms of disease. Also reported are responses obtained using the Cox method for linear regression analysis on non-parametric data, that gave information on the importance of various prognostic factors.

Adenocarcinoma↗
PubMedDate not supplied

Trials of single-agent and combination chemotherapy for advanced cancer of the pancreas.

In a study of 127 patients with advanced measurable pancreatic cancer, objective response rates of 2% (melphalan), 10% (5-FU and methyl-CCNU), and 7% (5-FU, methyl-CCNU, and streptozocin) were achieved. No responses occurred in the 28 patients treated with VP-16-213 who had already received prior chemotherapy. Toxicity was greater for the two- and three-drug combinations than for melphalan. There was no difference in survival following use of the three treatment regimens. Further studies are needed to develop effective chemotherapy for patients with cancer of the pancreas.

Antineoplastic Agents↗
PubMed1981

Antitumor effect of 3-[3-(2-chloroethyl)-3-nitrosoureido]-3-deoxy-D-glucopyranose on murine tumors.

The antitumor activity of a new derivative of nitrosourea, 3-[3-(2-chloroethyl)-3-nitrosoureido]-3-deoxy-D-glucopyranose (CNUG), against murine tumors was studied. CNUG showed remarkable antitumor activity against leukemias L1210 and P388, Lewis lung carcinoma, and sarcoma-180 (solid form). In particular, the majority of mice with leukemia or sarcoma-180 tumor were cured when they were given a single injection of CNUG on day 1 after tumor inoculation, and this treatment was more effective than daily treatment. CNUG was also active against sarcoma-180 grown in the brain, lung, liver or under the capsule of the kidney, and even against autochthonous lung tumor induced by 1-ethyl-1-nitrosourea. The number of peripheral leucocytes was depressed by the treatment with CNUG but this depression was less than that with 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea.

Animals↗
PubMed1984

[Intracranial ependymomas. Study of 81 cases and comparison with the literature].

For ten-years of period, between 1973-1982, 81 cases with intracranial ependymoma have been operated in H.U.T.F. Neurosurgery Department. Supratentorial localisation have been found in 24 cases (30%), and infratentorial in 57 (70%). 80% of the patients in supratentorial group and 91% in infratentorial group were under the age 20. In supratentorial group 79% were in paraventricular localisation, and 21% were intraventricular. In infratentorial group 70% of the cases were localised within the IV. ventricle, 20% in province of the tentorial roof, 5% in the lateral recessus and 5% into cerebellum. The 40 patients who were followed up were rated according to the localisation and the grades of the tumors, the type of the surgical intervention and chemotherapy with respect to the postoperative survival. As a result only the total resection of the tumor was found to be significant.

Adolescent↗
PubMed1984

Adjuvant therapy for carcinoma of the colon and rectum.

Because all types of cancer therapy are most effective when the tumor burden is small, adding adjuvant cancer treatment to surgical excision has great merit both in theory and experimentally. Even though large numbers of patients with large bowel cancer have been entered into various types of experimental trials over the past 25 years, the potential of multimodal cancer therapy has only been examined in a superficial manner at best. If this therapeutic approach had any substantial effectiveness, it would have long since become apparent. Surgical therapy is effective, with a five-year survival of 50%, and the various adjuvant therapies have shown only modest effectiveness when tested on patients with measurable disease. 5-Fluorouracil, with a response rate in measurable disease of approximately 20%, is the only consistently effective cancericidal drug, and its combination with other agents has thus far shown no increase in this response rate. Currently, available data would indicate a modest survival benefit from the use of postoperative 5-fluorouracil, particularly in patients with positive lymph nodes. There are a number of trials in progress studying the effectiveness of multiple drug combinations as well as combining chemotherapy with radiotherapy and/or immunotherapy in the adjuvant setting. Preliminary studies would suggest a benefit from infusing chemotherapy into the liver in the immediate postoperative period, although there has been no evidence substantiating improved survival from this approach. The multiple approaches for generating an effective immunologic response continue to be experimental and have little use in other than a highly controlled experimental environment. The use of radiotherapy as an adjuvant to surgery has been confined largely to patients with low-lying rectal cancer. There is substantial evidence that high-dosage radiotherapy for large bulky and fixed rectal cancer will result in shrinkage of the lesion, permitting more satisfactory surgical resection and decreasing the incidence of perineal recurrence. Evidence would also suggest that moderate-dosage preoperative radiotherapy may sufficiently alter cancer cells so that cells disseminated at the time of operation are no longer capable of growth. It has also been demonstrated that preoperative radiotherapy decreases the incidence of positive lymph nodes. Modest increase in survival following preoperative radiotherapy has also been demonstrated in numerous trials. Postoperative radiotherapy has not been tested for a sufficient period of time to either demonstrate its effectiveness or safety.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Agents↗