Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Lomustine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,585 records · Page 88Linked to original sources
PubMed1978

Rate of DNA synthesis as an indication of drug toxicity and as a guide for scheduling cancer therapy.

The rates of incorporation of [C3H3]thymidine into the DNA of tissues of normal mice at various times after single doses of several drugs (adriamycin, vincristine, methotrexate, 5-fluorouracil [5-FU], melphalan, CCNU, and chlorozotocin) that have some clinical activity against cancer have been determined and are considered to be indicative of the "degree of normalcy" of the respective tissues at those times. These experiments show that there are some differences and some similarities in the effects of the agents upon the various tissues of the mouse. Each of the agents caused early inhibition of incorporation of [C3H3]thymidine followed by stimulation of such incorporation by intestinal mucosa and marrow, but the timing and the extents of inhibition and stimulation differed for the various agents. Except for CCNU, the preceding description would also apply to the effects upon liver and lungs, but the stimulation was delayed in comparison to that of intestinal mucosa and marrow. Early inhibition with little subsequent stimulation occurred in the spleen, kidneys, and heart. For all tissues, recovery was slower and less extensive after CCNU than after the other agents. The data obtained with the single agents were used for setting up experiments in which a single dose of one agent was followed after selected intervals of time with a single dose of a second agent. The combination of adriamycin plus 5-FU was less toxic when the two agents were given simultaneously than when the 5-FU was given 24-96 hours after the adriamycin, while for the combination of adriamycin plus CCNU there was less toxicity if the CCNU was administered 24 hours after the adriamycin rather than simultaneously with it. When a combination of a single dose of methotrexate and a single dose of 5-FU was administered to mice, the lethality was greater when the two agents were administered 120 hours apart than when the two agents were given simultaneously or were separated by 24 or 48 hours; this was true regardless of which agent was administered first. These results are consistent with what might be predicted upon the basis of the data obtained for the single agents in this study and of what is known about the mechanisms of action of these agents and of the effects of the agents in relation to cell and tissue kinetics. These results indicate that patterns of thymidine fixation by tissues following single doses of agents might be useful in scheduling multiple-drug therapy to minimize host toxicity.

Animals↗
PubMed1984

[Secondary malignant tumors following treatment of Hodgkin's disease].

Secondary tumors were noted in 8 out of 675 patients with Hodgkin's disease during remission following treatment. The following diseases were diagnosed:acute myeloblastic leukemia (1), lung cancer (2), gastric cancer (3), cervical cancer (1), and basalioma (2). The incidence of secondary tumors among patients with Hodgkin's disease turned out to be much higher than in general population. Complications were more frequently observed in men after combined therapy (radio- and drug therapy).

Adult↗
PubMed1984

[Antitumor activity of a new nitrosourea, MCNU, on a cellular morphological basis evaluated by a new in vitro antitumor sensitivity assay].

Using our new in vitro antitumor sensitivity assay, the basis of which depends on predictive analysis of morphological findings of L1210 leukemia cells under the influence of antitumor agents, 5 kinds of nitrosoureas including MCNU were comparatively tested for antitumor activity. A cell killing effect became apparent very soon under BCNU and CCNU, rather late under Methyl-CCNU and MCNU, and intermediately under ACNU. Various cellular biological effects were apparently induced in L1210 cells by MCNU and its mechanism of action seemed to be broader than that of any other members of the nitrosoureas.

Animals↗
PubMed1983

Successful therapy of convoluted T-lymphoblastic lymphoma in the adult.

Fifteen adult patients with biopsy-proven convoluted T-lymphoblastic lymphoma were treated with an aggressive regimen, modified from the LSA2-L2 protocol used for childhood lymphoma. The treatment schema consisted of induction phase, including cyclophosphamide, vincristine, prednisone, adriamycin, and 2000 rads to mediastinum, as well as intrathecal methotrexate. Consolidation phase included cytosine arabinoside, 6-thioguanine, L-asparaginase, and CCNU, along with cranial irradiation and further intrathecal methotrexate. Maintenance consisted of cyclical chemotherapy and intrathecal methotrexate, continuing for a total of 3 yr. Median age in the group was 25 yr (range 16-73). There were 8 males and 7 females. At diagnosis, 9 patients had mediastinal involvement, and 9 had bone marrow involvement. Five of these demonstrated malignant cells in the peripheral blood. Complete clinical response was attained in 11 patients. Three patients achieved partial response. Four complete responders have relapsed, 1 in the central nervous system at 6 mo. and 1 in nodal sites at 3 mo, 1 in multiple sites at 24 mo. and 1 in bone marrow at 42 mo while off all chemotherapy for 6 mos. At this time, median survival of all patients is 28.3 mo. and median relapse-free survival is 21 mo. The median survival for complete responders in excess of 71 mo. while the median relapse-free survival for this group is 41 mo.

Adolescent↗
PubMed1983

Difference in effect of single immunosuppressive agents (cyclophosphamide, CCNU, 5-FU) on peripheral blood immune cell parameters and central nervous system immunoglobulin synthesis rate in patients with multiple sclerosis.

Cyclophosphamide (CY), 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 5-fluorouracil (5-FU) were given in single course schedules to chronic progressive multiple sclerosis (MS) patients clinically stable for 6 months. The following peripheral immune cellular parameters were measured before, during and after each drug administration: white blood count (WBC), polymorphonuclear count (PMN), lymphocyte count, percentage of T cells, T cell response to phytohaemagglutinin (PHA), percentage of B cells, percentage of cells bearing receptors for the Fc portion of immunoglobulin (% FcR cells), killer (K) cell activity defined by antibody-dependent cellular cytotoxicity (ADCC), and natural killer (NK) cell activity. Central nervous system (CNS) immunoglobulin G (IgG) synthesis was also measured. The patients were followed carefully by both quantitative and qualitative methods for any change in their neurologic condition. Selective reduction in NK activity was observed with CY and 5-FU while no significant alteration was seen in %FcR cells and K activity. CY differed from 5-FU in reducing lymphocyte count and B cell percentage while 5-FU decreased the percentage of T cells. CCNU, but not the other drugs, reduced T cell proliferative response to PHA. In addition, CCNU, which is known to penetrate well into the nervous system, caused a modest reduction in CNS IgG synthesis, while 5-FU had an uncertain effect. Clinically the patients were unchanged or continued to progress in their disability. The results suggest an independence of the CNS immune from the systemic immune system in MS in response to many immunosuppressive drugs.

Adult↗
PubMed1983

[Long-term survival and fatal late relapse in acute leukaemia in adults].

This study comprises 187 patients aged over 15 years with acute leukaemia, diagnosed and treated between the years 1969 and 1978. Fourteen (7.5%) survived for more than 5 years after diagnosis. In this group of survivors there were 7 patients with AML and 6 with ALL--corresponding to 8.9 and 21.4% of each collective, respectively--and 1 patient with PML. Four patients (28.6%) died after a survival time exceeding 5 years, 1 patient with AML as a result of a gastric carcinoma and the 3 other patients (1 AML, 2 ALL) of the original disease. Hence, survival times over several years do not necessarily mean real cures. From an analysis of our data, no factor correlating with long-term survival was identifiable. In terms of clinical-diagnostic parameters the group of late relapses was also heterogeneous.

Acute Disease↗
PubMed1983

[Combined treatment of malignant gliomas].

A controlled study of 226 age-matched patients with histologically proven grade 3 and 4 supratentorial gliomas with maximum feasible tumour resection, postoperative Karnofsky performance over 50 and minimum survival of 8 weeks compares the results of supportive care (45 cases), high-dose irradiation of 40 to 66 Gy (59 cases), COMP protocol (CCNU, procarbazine, vincristine, methotrexate, prednisone in 15 day cycles-42 cases) and simultaneous irradiation and COMP chemotherapy (80 cases including 30 survivors). Median recurrent-free intervals in the treatment groups (7 to 11.7 months) were significantly longer than after supportive care (4.4 months). Median survival with supportive care (6.7 months) was significantly shorter than after radiation or COMP treatment (11.7 and 12.3 months) and 14.9 to over 19.9 months with combined treatment, where the two-year survival rates were 33 and 67% (for survivors), and the 3-year survival rates 13 to 30%. Toxic side effects of multimodality treatment were more frequent than after chemotherapy. In addition to space-occupying intracranial cysts often simulating tumour recurrence (12%) and rare radiation necrosis, about 15% of long-term survivors developed progressive intellectual dysfunction with brain atrophy, in the absence of tumour regrowth. Despite some promising results of multimodality approaches towards the management of malignant supratentorial gliomas, the overall results are unsatisfactory and need further optimization.

Adult↗
PubMed1983

The effects of BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) and CCNU (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea) on glutathione reductase and other enzymes in mouse tissue.

BCNU has been reported to cause a rapid, irreversible inhibition of human erythrocyte glutathione reductase (GR) at chemotherapeutic dosage, without affecting metabolic enzymes. This inhibition may mediate some of the therapeutic and toxic effects of BCNU. Thiol containing agents such as reduced glutathione can protect cells against BCNU and a change in glutathione concentrations could modify BCNU effectiveness. At doses of 50 mg/kg (LD-50) and 100 mg/kg, i.p., BCNU decreased the activity of GR in mouse kidney, liver, brain, and heart with a greater loss in those animals which died from drug administration. GR activity tended to recover but still remained below control at 96 hours. Erythrocyte GR activity was reduced only at the higher BCNU dose. CCNU (100 mg/kg, i.p.) did not affect GR activity. BCNU also decreased creatine kinase, malate dehydrogenase, and lactate dehydrogenase activities. The inhibition of GR in vitro occurred only after biochemical reduction of the enzyme with NADPH. The oxidation state of GR may determine its sensitivity to BCNU in the human erythrocyte but we were unable to demonstrate an unusually high sensitivity or a specific effect of BCNU on GR in mouse tissues.

Animals↗
PubMed1983

Effect of partition coefficient on the ability of nitroimidazoles to enhance the cytotoxicity of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea.

The ability of three nitroimidazoles [SR-2508, misonidazole (MISO), and benznidazole] with differing octanol-water partition coefficients to enhance the cytotoxicity of the nitrosourea 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) was evaluated in two mouse tumors (the KHT sarcoma and the SCC VII/St carcinoma). These results were compared with the effect on two normal tissues (bone marrow CFU-S and testis spermatogonia). When given as a large single dose, benznidazole was more effective than MISO in enhancing the cytotoxicity of CCNU to both tumors. SR-2508 had no effect. The advantage of benznidazole over MISO was lost, however, because benznidazole gave more toxicity in the normal tissues than MISO. In experiments where the nitroimidazoles were administered by multiple small injections to maintain a blood plasma level between 50 and 100 micrograms/ml, benznidazole was also more effective than MISO in enhancing CCNU cytotoxicity in the tumors. In each case, enhancement was rather less than that obtained with large single injections. Again, however, benznidazole did not produce a consistently greater therapeutic gain than MISO because it also enhanced normal tissue toxicity while MISO did not. SR-2508 was ineffective in both tumors and normal tissues. We conclude that neither SR-2508 nor benznidazole are superior to MISO in combination with CCNU.

Animals↗
PubMed1984

Effects of carbamoylation on cell survival and DNA repair in normal human embryo cells (IMR-90) treated with various 1-(2-chloroethyl)-1-nitrosoureas.

The possibility was examined that the carbamoylating activity of some chloroethylnitrosoureas could interfere with the activity of normal human cells to survive treatment with these drugs; 1-(2-chloroethyl)-3-(trans-4-hydroxycyclohexyl)-1-nitrosourea, which has strong carbamoylating activity, inhibited the rejoining of drug or X-ray-induced DNA strand breaks in IMR-90 cells, whereas the noncarbamoylating cis-2-hydroxy isomer had little or no effect; 1-(2-chloroethyl)-3-(trans-4-hydroxycyclohexyl)-1-nitrosourea was twice as potent as the cis-2-hydroxy isomer in reducing colony survival. The moderate or high carbamoylating drugs 1,3-bis(2-chloroethyl)-1-nitrosourea and 1-(2-chloroethyl)-3-(cyclohexyl)-1-nitrosourea had effects resembling those of 1-(2-chloroethyl)-3-(trans-4-hydroxycyclohexyl)-1-nitrosourea. The low carbamoylating drug 1-(2-chloroethyl)-3-(2,6-dioxo-1-piperidyl)-1-nitrosourea had effects resembling those of the cis-2-hydroxy isomer. 1-(2-chloroethyl)-1-nitrosourea, although a strong carbamoylator in chemical systems, behaved biologically as if it were a low carbamoylator. This can be rationalized on the basis of limited cellular uptake of cyanate ion. The results suggest that carbamoylation may inhibit the nucleotide excision repair of chloroethylnitrosourea-induced DNA damage that may be crucial to the ability of normal human cells to recover from the action of these drugs. Previous work has indicated that susceptible human tumor cells are sensitive to chloroethylnitrosoureas because of a lack of a DNA repair protein (guanine O6-alkyltransferase) that is not involved in nucleotide excision repair. On the basis of these findings and other evidence, further clinical trials of appropriate noncarbamoylating chloroethylnitrosoureas would be justified.

Carmustine↗
PubMed1984

Growth response of B16 melanoma to in vivo treatment with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) at the initial stage after tumor transplantation.

The changes of implanted B16 melanoma fragments in situ following early treatment with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) were studied by quantitative histopathologic methods from Day 1 to Day 7 and at Day 14 after transplantation. During the first 3-day period there were no apparent differences between the two groups in all the parameters studied. The most striking differences were observed on Day 5 after implantation, when the drug-treated tumor showed the lowest number of morphologically intact tumor cells and the lowest level of proliferative capacity, with a high proportion of melanotic cells. The late infiltration of host macrophages was more abundant in drug-treated tumors than in controls due to an enhanced production and liberation of melanin granules. The results suggest that a 7-day growth delay of drug-treated tumors is characterized not only by a reduced number (one order of magnitude) of intact tumor cells but also by a severely suppressed proliferative capacity.

Animals↗
PubMed1978

[Non resectable colonic cancer. Results from a test of chemotherapy with simultaneous prescription of VM26, methyl-CCNU and 5 fluoro-uracile (author's transl)].

Thirty nine patients with non resectable colonic carcinoma entered into a phase II combination chemotherapy trial. The patients were treated with a sequential cyclic combination of 3 drugs: VM 26 (60 mg/m2), methyl-C.C.N.U. (120 mg/m2) and 5 fluoro-uracile. Seventeen patients out of 39 (43.6%) are considered as good responders. The median survival time of the overall of this group is 12.6 months; it is of 15,6 months for good responders and of 7 months for non responders. The simultaneous application of B.C.G. do not change neither the level of responses nor the median of survival time. The good tolerance of this protocol let us to propose this combination as an adjuvant treatment for patients surgically treated for a Dukes'C colonic cancer.

Adult↗
PubMed1984

[Combination chemotherapy with vincristine, melphalan, CCNA, cyclophosphamide, prednisone in myeloma].

The authors report the results of a prospective, multi-centre trial involving 87 patients with previously untreated myeloma who were treated by combination chemotherapy consisting of melphalan, cyclophosphamide, CCNU, prednisone and vincristine. 83.1% of patients had a high tumour mass (stage III on Durie and Salmon's classification). The response to treatment could be evaluated in 76 patients and 70% were found to respond. The median actuarial survival of the whole population is 30 months. The survival is significantly longer (p less than 0.001) in responders (median 40 months) than in non-responders (median: 17 months); the survival is significantly shorter (p less than 0.01) in subjects with renal failure (median: 10 months) than in subjects without renal failure (median: 36 months). This treatment is sufficiently well tolerated to be administered on an outpatient basis. One case of acute monoblastic leukaemia was observed. These results are similar to those reported in the literature.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1977

[Chemotherapy in bronchogenic carcinoma (author's transl)].

Therapy results in bronchogenic carcinoma remain unchanged since the establishment of thoracic surgery. Prognosis depends on the two main factors: histological type and extension of disease at the time of diagnosis. Both factors are mutually dependent. Small cell carcinoma of the bronchus represents a special entity with its early hematogenous spread and the poorest prognosis of all bronchogenic carcinomas. The tumor is highly sensitive to radioor chemotherapy. A marked prolongatoion of medium survival time can be obtained by combination chemotherapy. This is usually accompained by an obvious improvement in the patient's general condition. In certain cases results can be further improved by irradiation of the primary tumor and the mediastinum. Prophylactic cranial irradiation is often indicated because of the frequent cerebral metastases. Results of chemotherapy are much less impressive in adenoor squamous-cell carcinomas of the bronchus. Such therapy can only be recommended for the exceptional case. Pilliative radiotherapy should be used freely. Till now, adjuvant chemotherapy after surgery has only proven its value in small cell bronchogenic carcinoma.

Antineoplastic Agents↗