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At least 325 records · Page 18Linked to original sources
PubMed1989

Adjuvant therapy of colorectal cancer: where do we stand?

The value of adjuvant therapy for colon and rectal cancer has been studied extensively in clinical trials. Data from earlier trials suggested some potential benefit for rectal cancer patients but minimal if any benefit for patients with Dukes' B2, B3 or C colon cancer. More recent data demonstrate that combined irradiation plus chemotherapy is useful in rectal cancer and that postoperative chemotherapy may have a small benefit as adjuvant treatment in patients with adenocarcinoma of the colon. Whether the recently reported statistically significant results in the adjuvant therapy of colon cancer are clinically significant is still being debated. A number of clinical trials evaluating biological response modifiers, regional chemotherapy, and tumor vaccines are either still under way or in the process of evaluation. The results of these trials may significantly enhance the therapeutic options available to clinicians managing patients with resected large bowel cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1978

Male sterility in the domestic fowl (Gallus domesticus) after 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitroso-trans-urea (NSC-95441) treatment of chicks.

Of 11 male baby chicks treated twice with 3 mg of 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitroso-trans-urea (once on the day of hatching and once on the day after), 9 showed absolute lack of spermatogenesis and 2 showed severe inhibition when examined at the age of 6 months. Plasma testosterone level was not altered, however, and histologic examination revealed well-organized testicular interstitial tissue with an abundance of Leydig's cells. In the lining of the seminiferous tubules only Sertoli's cells were present. The weight of the testes from treated animals was only about 10% of control weight. These findings emphasized the possibility that the nitrosoureas cause severe damage to the reproductive system in man.

Animals↗
PubMed1987

Glutathione and related enzymes in rat brain tumor cell resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea and nitrogen mustard.

Reduced glutathione (GSH) and activities of several glutathione-related enzymes were measured in two 9L rat brain tumor cell lines with differing sensitivities to both 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and nitrogen mustard. GSH, measured by a specific high-performance liquid chromatographic method, was found to be approximately twice as high in 9L cells sensitive to BCNU but resistant to nitrogen mustard. The nitrogen mustard resistant cell line was also found to have 2.5-fold more bulk glutathione transferase activity and approximately 3-fold more gamma-glutamyl transpeptidase activity. Glutathione reductase activity, protein thiol, and total protein content were similar in the two cell lines. Pretreatment of 9L cells with 50 microM buthionine sulfoximine for 24 h to deplete GSH only slightly potentiated BCNU cytotoxicity in a clonogenic assay whereas that of nitrogen mustard was markedly potentiated in both cell lines. Similarly, buthionine sulfoximine pretreatment had little effect on the induction of sister chromatid exchanges by BCNU, but significantly increased the number of sister chromatid exchanges induced by nitrogen mustard in both cell lines. Depleting GSH also had no significant effect on the cytotoxicity of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea to 9L cells. Pretreatment of 9L cells with 1 mM GSH significantly protected against nitrogen mustard cytotoxicity. Moreover, nitrogen mustard incubated with GSH and glutathione transferase was 4-fold less cytotoxic than nitrogen mustard incubated with GSH alone. Incubation of BCNU with GSH alone or with glutathione transferase had no effect on BCNU cytotoxicity. These results indicate that elevated GSH and glutathione transferase activity is one mechanism of cellular resistance to nitrogen mustard in the 9L cell line, but it does not correlate with resistance to BCNU or other clinically important nitrosoureas.

Animals↗
PubMed1987

A method to determine the carbamoylating potential of 1-(2-chloroethyl)-1-nitrosoureas.

1-(2-Chloroethyl)-1-nitrosoureas (CNUs) are alkylating agents that also possess carbamoylating activity, depending on the chemical nature of the substituent at N-3. Although effects on a variety of enzymes, including inhibition of glutathione reductase (GS-R) have been attributed to carbamoylation, the biological significance is still not well understood. This deficiency is due at least in part to the analytical method that has been used to measure carbamoylation:in-vitro reaction with the omega-amino group of lysine. Reaction of CNUs with glutathione (GSH) offers a better estimation of carbamoylating potential in vitro. The decrease in free thiol groups during incubation of GSH with various CNUs can be followed using the thiol reagent 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB). With this test, carbamoylating potential relative to that of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) as 100% was 94% for 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU), 86% for 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), 16% for 1-(2-chloroethyl)-3-(2-hydroxyethyl)-1-nitrosourea (HECNU) and 6% for chlorozotocin (CLZ). Various carbamoylated and alkylated GSH derivatives, such as S-(2-chloroethylcarbamoyl)-, S-(2-hydroxyethylcarbamoyl)-, S-(cyclohexylcarbamoyl)-, S-(4-methylcyclohexylcarbamoyl)- and S-(2-hydroxyethyl)glutathione, are formed on incubation of GSH with CNUs. High-performance liquid chromatography (HPLC) revealed that, in comparison to carbamoylated compounds, alkylated GSH derivatives are formed in only low yields (less than 3%). Formation of carbamoylated products during incubation correlated with the decrease in free thiol groups. Concentrations achieving 50% GS-R inhibition in vitro were 0.16 mM for BCNU and 1.9 mM for HECNU.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkylating Agents↗
PubMed1979

[Initial experiences with a nation-wide Austrian study of adjuvant chemo- and immunotherapy of colorectal cancer following radical surgery].

The outline of a cooperative study for adjuvant Chemo-Immunotherapy on radically operated Colon-Rectum-Carcinoma, is presented. One group of patients receiving Placebo, has to be randomized against another group who postoperatively received Chemo-Immunotherapy consisting of 5-Fluorouracil and CCNU and Corynebacterium parvum, which was administered intermittently, throughout one year. Patients with Rectum-Carcinoma additionally receive radio-therapy with 1500 rad HD before surgery and 4500--5000 rad HD postoperatively with Cobalt-60. The central documentation, and randomization, is provided at the Institute for Cancer Research of the University of Vienna.

Antineoplastic Agents↗
PubMed1987

Chemo- and immunotherapy of an adenovirus-induced transplantable sarcoma in hamsters.

The subcutaneous transplantable adenovirus sarcoma (TAVS) in hamsters was created in 1972 at the Oncological Research Institute and maintained by serial subcutaneous transplantation. It showed the highest sensitivity against some alkylating drugs and antimetabolites--cyclophosphamide, sarcolysine, methotrexate and 6-mercaptopurine. In some degree, TAVS is able to differentiate antitumor drugs of one group by the intensity of their antitumor activity. Among the drugs, cyclophosphamide was the most active and 6-mercaptopurine and 5-fluorouracil the least active. Antitumor drugs of plant origin, antibiotics and methyl-CCNU had a weak activity on subcutaneous TAVS. Intramuscular TAVS showed a similar sensitivity, with some differences for olivomycin, bruneomycin and vinblastine. Intracerebral TAVS was sensitive against antitumor agents penetrating through the hemato-encephalic barrier and which were active against its subcutaneous and intramuscular form. BCG vaccine and levamisole applied separately did not show any activity on the growth of TAVS. Combined immunochemotherapy with cyclophosphamide plus BCG gave a better enhancement of the antitumor effect of the cytostatic than that of the combination of methotrexate plus BCG and cyclophosphamide plus levamisole. These results showed that TAVS in hamsters may be used as a suitable experimental model for pharmacological studies of antitumor agents and combined immunochemotherapy.

Adenoviridae Infections↗
PubMed1988

Immunochemosurgery as a new approach to reasonable treatment of advanced cancer.

To evaluate the effectiveness of adjuvant immunochemotherapy in advanced adenocarcinoma of stomach, patients who had undergone radical subtotal gastrectomy for stage III gastric carcinoma were randomized to receive immunochemotherapy or not. For immunotherapy, streptococcus pyogenes preparation (picibanil) was given intramuscularly every week and for chemotherapy, either MFC (mitomycin-C, 5-fluorouracil and cytosine arabinoside) regimen or FME (5-fluorouracil and methyl-CCNU) regimen was given. Immunotherapy was started at the 4th or 5th postoperative day and chemotherapy was started at the 8th to 10th postoperative day. To evaluate the immune status of patients, various immune parameters such as 1-chloro-2, 4-dinitrobenzene (DNCB) test, T-lymphocyte count, PHA- and concanavalin-A stimulated lymphoblastogenesis and antibody dependent cellular cytotoxicity (ADCC) activity were checked before operation and 3 to 4 months after operation. One hundred and thirty-eight patients were chosen for study during a 5-year period. Seventy-four patients received postoperative immunochemotherapy and 64 patients received no further anticancer therapy following operation. All patients had been followed at least for 5 years since they underwent operation. Survival rate and immune status were compared between two groups. Patient characteristics and preoperative values for immune status of two groups were similar to each other. Five-year survival rate of postoperative immunochemotherapy group was 44.6%, whereas that of surgery alone group was 23.4%. The difference is statistically significant (p less than 0.05). All the postoperative values of immune parameters showed more favourable data in the postoperative immunochemotherapy group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMedDate not supplied

Phase I trial of ftorafur combined with mitomycin C or methyl-CCNU in gastrointestinal cancers.

Twenty-five patients with disseminated gastrointestinal malignancies were treated in a phase I study with a combination of ftorafur and mitomycin C or florafur and methyl-CCNU. Most patients had been heavily treated previously. Gastrointestinal, central nervous system, and marrow toxicity were manageable. Tumor regression was noted in five of 25 patients. A large-scale phase II study in untreated patients with gastrointestinal malignancies appears indicated with a combination of these agents.

Adenocarcinoma↗
PubMed1977

Phase II study of oral methyl-CCNU and prednisone in previously treated alkylating agent-resistant multiple myeloma.

Thirteen patients with multiple myeloma (MM) who either failed to respond to or who were relapsing from standard agents and who received four or more courses of methyl-CCNU + prednisone (adequate drug trial) are reported in this paper. Methyl-CCNU was given orally before breakfast at 6-week intervals at a starting dose of 50 mg/m2 with the intention of increasing the dose to 100, 150, and 200 mg/m2 with each subsequent course. The dose of prednisone was 75 mg/day x 7 with each course. The response rate was 46% (six of 13 patients). No patient had better than a fair response. Drug toxicity, severe enough to prevent further dose escalation, was observed in every case. Prior BCNU therapy or the lack of response to previous alkylating agents did not prevent a response to methyl-CCNU + prednisone. The response rate of methyl-CCNU + prednisone in MM is comparable to the results achieved with other agents in similar groups of patients.

Administration, Oral↗
PubMed1977

Combination chemotherapy for disseminated malignant melanoma with DTIC, vincristine, and methyl-CCNU.

Thirty patients with disseminated melanoma were treated with DTIC (250 mg/m2 for 5 consecutive days every 3 weeks), methyl-CCNU (175 mg/m2 orally every 6 weeks), and vincristine (1.4 mg/m2 weekly x 6 and then every 3 weeks). Seven patients died within 3 weeks of the start of chemotherapy. There was a 30% response rate (seven partial and two complete remissions) for all patients and a 39% response for evaluable patients. The median survival was 45 and 18 weeks respectively for responders versus non-responders and 22 weeks for all evaluable patients.

Adult↗
PubMed1987

The effects of liver directed radiotherapy and chemotherapy on liver function tests and hematological parameters in patients with surgically resected colon cancer: findings from the Gastrointestinal Tumor Study Group.

The effects on liver function tests of liver-directed radiation (RT) and systemic chemotherapy (CT) were examined at 6 months after initiation of treatment on two Gastrointestinal Tumor Study Group protocols. Data from patients on protocol GI 6175 (adjuvant CT or no adjuvant therapy) were used to evaluate the effect of CT alone, and data from patients on protocol GI 6179 (adjuvant CT plus liver directed RT or no adjuvant therapy) were used to evaluate the combined effects of CT and RT. Finally, data from patients on GI 6179 who received less than protocol specified RT doses were used to determine whether minor differences in dose are detectable via liver function tests. In 40 patients receiving CT, the serum level of alkaline phosphatase was not significantly increased (p = 0.14) compared to that of control patients whereas the level of serum glutamate oxoloacetate transaminase was significantly elevated (p = 0.03). In 31 patients receiving both CT and RT, both alkaline phosphatase and SGOT were significantly elevated (both p = 0.03). In addition, in 19 patients who received less than full RT doses, the changes in dose were not detectable from those patients who received full dose (all p greater than 0.10). In summary, CT alone may elevate hepatocellular enzymes, whereas a combination of CT and liver-directed RT is associated with a significant increase in both SGOT and alkaline phosphatase. Small alterations in the dose of volume of RT are not detectable by liver function test variations.

Alkaline Phosphatase↗