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At least 343 records · Page 19Linked to original sources
PubMed1987

Cytostatics for acromegaly. Marked improvement in a patient with an invasive pituitary tumour.

A 21-year-old woman suffering from acromegaly was treated with transsphenoidal subtotal hypophysectomy (microscopy: acidophilic adenoma), followed by x-ray and bromocriptine therapy. Seven years later she was re-operated because of a partial bitemporal loss of vision, intracranial hypertension, and regrowth of the pituitary tumour seen on CT-scan. A large part of the invasive suprasellar tumour was then removed by transcranial approach. The neurosurgery was followed by cobalt radiotherapy and bromocriptine administration. Two years later, symptoms and signs of tumour growth reappeared. Administration of cytostatics, such as doxorubicin (Adriamycin) and lomustine (Belustine), resulted in distinct clinical improvement associated with a seven-fold decrease in the serum growth hormone concentration. The visual field became normal and the intracranial mass on a CT scan decreased markedly. As a result the patient was able to resume work.

Acromegaly↗
PubMed1987

Age-associated sensitivity to experimental, drug-induced marrow hypoplasia in laboratory rats.

Treatment of adult rats of three age groups (8, 11 and 29 weeks) with haematotoxic doses of three different cytostatic agents (cyclophosphamide, 5-(2-dimethyl-aminoethoxy)-7-oxo-7H-benzo(c)fluorene, and lomustine) demonstrated a tendency to lower the sensitivity of elder animals to cytotoxic effects. The influence of age was especially distinct in changes of the reticulocyte or segmented neutrophil counts after all drugs tested. Changes in marrow nucleated erythroid cell counts were not significantly influenced by age. Reactions of other characteristics also depended on this factor but not following the administration of every drug.

Abnormalities, Drug-Induced↗
PubMed1986

Effect of alkylating drugs on rat cerebellum.

Ultrastructural and histochemical studies were performed on Wistar rats treated during 6 days with Cyclophosphamide 50 mg/kg/day or Lomustine 20 mg/kg/day. Changes in cerebellum after both drugs were similar. Most severe ultrastructural lesions were found in glia, mainly astroglia cells localized in perivascular area. Cytoplasm of these cells was on the large area devoid of organelles. Neurons were less affected but in Purkinje cells mild ultrastructural lesions were found. Increased activity of glucose-6-phosphatase and decreased of succinate dehydrogenase activity in these cells suggest that cytostatic treatment disturbed metabolism in the neurons.

Acetylcholinesterase↗
PubMed1987

Effect of inhibition of glutathione reductase by carmustine on central nervous system oxygen toxicity.

Exposure of animals to O2 at increased partial pressures above 2.5 atmospheres absolute results in seizures. The endogenous intracellular antioxidant defense mechanisms are thought to play a protective role in mitigating such seizures. Investigations were carried out to determine if inhibiting brain glutathione reductase with carmustine would result in an alteration in time to seizures of rats exposed to high pressure O2. Treatment of air-breathing rats with carmustine (12.5, 25 and 50 mg/kg i.v.) resulted in a dose-dependent decrease (P less than .001) in whole-brain glutathione reductase activity without affecting the activities of the other components of the antioxidant defense mechanisms determined. This treatment also resulted in a dose-dependent decrease (P less than .001) in time to seizure of rats exposed to four atmospheres absolute O2. Conversely, treatment of rats with lomustine (30 mg/kg i.v.), a nitrosourea compound related to carmustine, failed to affect the activity of brain glutathione reductase or any other component of the antioxidant defense mechanism determined, or did it influence the seizure time of rats exposed to four atmospheres absolute O2. These results suggest that glutathione reductase is an integral component of the antioxidant defense mechanisms. Inhibition of this enzyme results in an alteration in sensitivity of the organism to the toxic effects of O2.

Animals↗
PubMed1985

Randomized trial of combination chemotherapy in hormone-resistant metastatic prostate carcinoma.

A prospective randomized study was conducted in 51 patients with stage D hormone-resistant prostatic carcinoma, comparing a combination of doxorubicin and lomustine (DC) with cyclophosphamide and 5-FU (CF). Patients were assessed objectively (employing National Prostate Cancer Project criteria) and subjectively (using a numerical scoring scheme). Each regimen was well tolerated with acceptable levels of myelosuppression. The objective partial response rate was 57% for DC and 8% for CF. Objective stabilization occurred, respectively, in 14% and 44% of the patients. Similarly, DC demonstrated a significantly superior subjective response rate (partial plus complete) of 82%, compared to 48% for CF. Patients with poor initial performance status or liver involvement had significantly lower response rates and reduced survival. Overall, there was no significant difference in survival between the two arms, reflecting the similarity between DC and CF in total objective response rate (partial response plus stable disease). DC provided superior palliation and was well tolerated by an essentially geriatric population.

Aged↗
PubMed1984

Effects of amphotericin B with combination chemotherapy on response rates and on survival in non-small cell carcinoma of the lung.

Thirty-seven patients with non-small cell carcinoma of the lung were randomized to receive doxorubicin, lomustine, hexamethylmelamine, and methotrexate (ACHM) or ACHM plus amphotericin B (AMB). The complete plus partial response rate was 39% for ACHM plus AMB, compared to 23% for ACHM alone. However, the median duration of complete or partial response was only 3.0 months with ACHM plus AMB, compared to 7.0 months with ACHM. Most importantly, median survival was only 4.0 months with ACHM plus AMB, compared to 8.0 months with ACHM (P = 0.08; two-tail test). Myelosuppression was enhanced by the addition of AMB. Although AMB has biological and antitumor activity in certain clinical circumstances, it does not appear to have a meaningful role in palliative therapy of patients with non-small cell bronchogenic carcinoma.

Altretamine↗
PubMed1981

Combined modality treatment of small cell carcinoma of the lung.

Ninety patients with extensive and 61 with limited small cell carcinoma of the lung were treated with three courses of intravenous chemotherapy (cyclophosphamide, doxorubicin hydrochloride, and vincristine sulfate) followed by radiotherapy to intrathoracic disease, and a second three-drug oral combination consisting of lomustine, procarbazine, and methotrexate for one year. Among the 147 patients who were evaluated, 55 of 66 (83%) with limited disease and 53 of 81 (65%) with extensive disease showed response after three courses of chemotherapy. The complete response rate in patients with limited disease prior to radiotherapy was 24%, but increased to 58% when evaluated following radiotherapy. The median survival was 47 weeks for patients with limited disease and 36 weeks for those with extensive disease. A 24% two-year survival is projected for complete responders. Important prognostic factors for survival are performance status, extent of disease, and sex, with female subjects doing somewhat better than male subjects. Among patients with limited disease, 45% failed within the CNS despite the use of chemotherapeutic agents that cross the blood-brain barrier. The initial induction regimen and radiotherapy were well tolerated; the oral three-drug combination was more toxic and did not prevent CNS metastases.

Adult↗
PubMed1982

Tumor size, response rate, and prognosis in small cell carcinoma of the bronchus treated by combination chemotherapy.

Ninety-eight patients with small cell carcinoma of the bronchus (SCCB) were treated with a combination of cyclophosphamide, methotrexate with calcium leucovorin rescue, and lomustine (CCNU). VP-16-213 was given on relapse. Response rate and survival were analyzed according to extent of tumor, presence of the syndrome of inappropriate antidiuretic hormone production (SIADH), and, in 38 patients, size of intrathoracic tumor as measured by computerized tomographic (CT) scanning. The median survival of the entire group was 34.6 weeks. In patients with limited disease the median survival was 46 weeks compared to 29 weeks for those with extensive disease. This difference in survival between patients with limited and extensive disease was most marked in those showing a partial response (median survival, 45.9 and 28 weeks, respectively). Patients with ectopic antidiuretic hormone production had a poor prognosis even if they had achieved a complete response. Only one partial response to VP-16-213 occurred. There was a strong correlation between initial intrathoracic tumor size as assessed by total cross-sectional area on CT scan and response and survival. When the total area exceeded 30 cm2 there were no complete responders, but there were complete responses in eight of 21 patients when the area was less than 30 cm2. The relationship between intrathoracic tumor size and response rate was present when analyzed according to disease extent, age, sex, and performance status. A clear relationship between total tumor area and survival was also found. When SCCB is treated with chemotherapy alone, the prognosis is better for those patients who present with limited disease, without SIADH, and with small intrathoracic tumor. In this group it is possible that further intensification of therapy may result in prolonged survival.

Adult↗
PubMed1982

Chemotherapy versus chemoimmunotherapy with levamisole or Corynebacterium parvum in advanced lung cancer.

A total of 109 patients with advanced lung cancer, all cell types, were randomized between MACC chemotherapy only, consisting of methotrexate, doxorubicin (Adriamycin), cyclophosphamide, and lomustine (CCNU); MACC plus levamisole (LMS) orally; and MACC plus Corynebacterium parvum (CP) sc. Of these patients, 101 were evaluable, with no differences among the three treatment groups for overall response rate and survival time. Objective response rates and median survival times were 41% and 230 days for patients given MACC only, 39% and 257 days for those given MACC plus LMS, and 44% and 223 days for those given MACC plus CP, respectively. There was a significant increase in survival for patients with large cell anaplastic carcinoma receiving CP or LMS, particularly in the good-performance-status category. Pretreatment delayed cutaneous hypersensitivity to recall antigens in 50 patients had prognostic significance, but repeat tests after 2 months of treatment in 30 patients did not show different patterns of conversion among the three groups. There was no difference in hematologic toxicity among the three groups. With the possible exception of large cell anaplastic carcinoma, immunotherapy with LMS or CP as given in this trial does not appear to be therapeutically advantageous in advanced lung cancer.

Adenocarcinoma↗
PubMed1982

CCNU, vincristine, methotrexate, and procarbazine treatment of relapsed small cell lung carcinoma.

Thirty-two patients with refractory relapsed small cell carcinoma of the lung (SCCL) were treated with a combination of CCNU (lomustine), vincristine, methotrexate, and procarbazine (COMP); 29 were evaluable for response. Nine patients (31%) had responses: five complete responses (CR) and four partial responses. Patients with CR had a median survival of 11 months (range, 51/2-141/2) from the start of COMP. Patients with less than CR had a median survival of approximately 3 months (range, less than 1-7). The comparison of CR versus less than CR is significant (P = 0.003). Patients achieving CR usually had limited disease and four of the five who achieved CR survived greater than 6 months. The regimen was well-tolerated, but myelosuppression was seen in all patients. COMP appears to be a useful combination in patients with relapsed SCCL. Aggressive retreatment should be considered in relapsed patients with this disease since some may achieve a second CR, with the associated potential survival benefit.

Administration, Oral↗
PubMed1984

Comparison of combination chemotherapy programs in advanced adenocarcinoma-large cell carcinoma of the lung: a North Central Cancer Treatment Group study.

One hundred and six patients with advanced adenocarcinoma and large cell carcinoma of the lung with no prior chemotherapy were entered in a prospectively randomized trial comparing cyclophosphamide, doxorubicin, and cisplatin versus methotrexate, doxorubicin, cyclophosphamide, and lomustine. The two regimens resulted in nearly identical regression probabilities (36% vs 34%), distributions of time to progression, and survival distributions. The major toxic effects from both regimens consisted primarily of myelosuppression and nausea and vomiting, with severe vomiting occurring more frequently in patients treated with cyclophosphamide, doxorubicin, and cisplatin (43% vs 19%).

Adenocarcinoma↗
PubMed1984

Potentiation of cytotoxicity of anticancer agents by several different polyene antibiotics.

The ability of several different polyenes to potentiate the cytotoxicity of carmustine, lomustine (LOM), and doxorubicin (DX) against AKR mouse leukemia was quantitated. All polyenes could potentiate the cytotoxicity of the anticancer agents; however, the methyl ester derivatives of the heptaenes amphotericin B and candicidin and the triene trienine were most effective with potentiations in the order of ten thousandfold for DX and LOM. A steep dose-response relationship for the polyenes was also noted. Neither the toxicity of the polyenes nor their level of potentiation could be correlated with structure or class.

Animals↗
PubMed1982

Salvage chemotherapy for non-Hodgkin's lymphoma.

Nineteen patients with advanced non-Hodgkin's lymphoma resistant to previous chemotherapy were treated with combination chemotherapy consisting of lomustine (CCNU), cytarabine, and prednisone. Eight patients (42%) had complete remission and four (21%) had partial remission. The median survival time of the 19 patients was greater than 14 months. The eight patients who had complete remission were still alive as of May 1, 1982, with a median follow-up time of 632 days (range, 365-1247). We believe that this combination chemotherapy scheme warrants further investigation.

Adult↗
PubMed1993

Vitamin D3, a possible nuclear protector in normal hepatic and medullar tissue in white Wistar rats treated with cytostatics. Radioisotopic and cytogenetic aspects.

Vitamin D3 was given to male Wistar rats in 3 doses totalling 10,000 IU/kg b.w. then, within 24 hrs, girostan (10 mg/kg b.w.), lomustin or CCNU (10 mg/kg b.w.), all cytostatic substances, were injected in a single dose. Association of vitamin D3 with these cytostatics was found to reduce incorporation of 3H thymidine and a return to normal of RNA synthesis. This suggests that vitamin D3 has a protective effect by maintaining the stability of the double helix. Cytogenetically, the level of the recombinations and of the lesions themselves changes in relation to the structure of the alkylant used, and the damage is smaller if vitamin D3 is given before cytostatics.

Animals↗
PubMedDate not supplied

MOPP/ABV/CAD chemotherapy with and without recombinant human granulocyte-macrophage colony stimulating factor in untreated, unfavorable prognosis Hodgkin's disease.

Seventeen consecutive patients with previously untreated poor prognosis Hodgkin's disease (clinical stage II and III with systemic symptoms, and stage IV) received 6 courses of aggressive chemotherapy, with (9 patients) and without (8 patients) the addition of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF). Chemotherapy (MOPP/ABV/CAD regimen) included full doses of nitrogen mustard, lomustine (CCNU), vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine and bleomycin, and was administered between days 1 and 15 of each course. Course were planned for 28-day intervals. rhGM-CSF was given at a dose of 5 micrograms/kg/day subcutaneously from day 16 to 26 of each course. With cytopenia (i.e. white blood cell, WBC, count < 3.0 x 10(9)/L and/or platelet count < 100 x 10(9)/L) delaying courses was preferred to administering reduced drug dosages. Substantial delays (ranging from 7 to 28 days) in delivering cytostatics were necessary between 70% of courses. The cumulative mean number of days for which the courses had to be delayed before completing the 6 MOPP/ABV/CAD courses was 57. The percentage of planned doses of cytotoxic drugs (nitrogen mustard, melphalan, epidoxorubicin, procarbazine) actually administered was 92%. Causes of treatment delay were presented by leucopenia in 82% and by leuco-thrombocytopenia in 23% of the courses. The WBC nadir was constantly encountered at day 20-21 following completion of courses, and slightly worsened with subsequent courses. The decrease in platelet values was milder than that in WBC counts. There were no differences in any of the above parameters between patients treated with MOPP/ABV/CAD alone or followed by rhGM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) modulates rat liver microsomal cyclophosphamide and ifosphamide activation by suppressing cytochrome P450 2C11 messenger RNA levels.

The alkylating anticancer drug 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU; lomustine) is frequently administered to cancer patients as part of a combination chemotherapy regimen. Previous studies have indicated that CCNU treatment of adult male rats leads to prolonged decreases in liver cytochrome P450 (CYP)-mediated enzyme activities. Because the alkylating agent prodrugs cyclophosphamide and ifosphamide are known to be activated by liver cytochrome P450 enzymes, the potential for interaction between CCNU and these oxazaphosphorines was examined. Treatment of adult male rats with a single dose of CCNU (30 mg/kg i.p.) resulted in a progressive loss of liver microsomal cyclophosphamide and ifosphamide hydroxylation activities in vitro (30-60% decrease after 7-27 days). The individual liver P450 forms modulated by CCNU were then identified using P450 form-specific microsomal testosterone hydroxylase assays. CCNU treatment was found to decrease substantially CYP2C11-dependent testosterone 2 alpha-hydroxylase activity (80-90% decrease after 14 or 27 days), but it did not affect CYP3A2-dependent testosterone 6 beta-hydroxylase activity. It only modestly decreased CYP2A2-mediated testosterone 15 alpha-hydroxylase activity. The reduction in CYP2C11 activity was not associated with a decline in liver microsomal NADPH-cytochrome P450 reductase activity, but rather was caused by a complete suppression of CYP2C11 mRNA levels. In contrast to other alkylating agents, such as cisplatin, which is known to feminize the overall expression profile of gender-specific liver enzymes, CCNU did not increase levels of the female-predominant liver enzymes steroid 5 alpha-reductase and CYP2C7, nor did it deplete circulating testosterone levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Corticosteroid is not beneficial in multiple-drug combination chemotherapy for multiple myeloma. Finnish Leukaemia Group.

In a randomised multicentre trial a combination of methylprednisolone, vincristine, lomustine, cyclophosphamide and melphalan (MOCCA) was compared with the same regimen omitting methylprednisolone after the first course (COLA) in previously untreated patients with multiple myeloma. The MOCCA arm showed a response rate of 72% among 79 patients and the COLA arm a response rate of 60% among 59 patients. This difference was not statistically significant. The median survival time was 56 months in the MOCCA arm and 61 months in the COLA arm. There was a slight increase of early deaths (within the first 6 months) in the MOCCA arm as compared with the COLA arm. We conclude that, in multidrug therapies, the continuation of corticosteroid at conventional dosage beyond the first course does not improve response rate or survival time in multiple myeloma.

Adult↗
PubMed1997

Role of O6-methylguanine-DNA methyltransferase in the resistance of pancreatic tumors to DNA alkylating agents.

Pancreatic adenocarcinomas rarely respond to radiation or chemotherapy, indicating that a large percentage of these tumors possess complex mechanisms of resistance. The failure of alkylating agents, such as carmustine [1,3-bis(2-chloroethyl)-1-nitrosourea; BCNU], lomustine [1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea; CCNU], and streptozotocin, to yield consistent therapeutic results further suggests that one of these mechanisms may be the high expression of O6-methylguanine-DNA methyltransferase (MGMT). All 12 human pancreatic ductal adenocarcinomas assayed for MGMT activity showed unusually high levels, implying that these malignancies are efficient in repairing genotoxic O6-alkylguanine lesions induced by methylating (streptozotocin) and 2-chloroethylating (BCNU and CCNU) chemotherapeutic genotoxic agents. Immunohistochemical analysis of an additional 15 pancreatic tumors showed that high levels of MGMT protein reside in the nucleus and the cytoplasm of malignant cells. Both nuclear and cytoplasmic staining were absent in hyperplastic duct epithelium, but staining was invariably present in moderate to highly dysplastic foci and especially strong in invasive components of the tumor. With the exception of lymphocytes that were MGMT positive, acinar, ductal, and islet cells did not stain for MGMT in histologically normal pancreata. These data indicate that MGMT activity is up-regulated in dysplastic epithelium, and its expression increases during tumor progression, reaching the highest levels in the invasive components of the tumor. Resistance of pancreatic tumor cells to alkylating agents was verified with four pancreatic tumor cell lines. CAPAN-2, CFPAC-1, PANC-1, and MIAPaCa-2, having MGMT levels of 1800, 987, 700, and 880 fmol/mg protein, respectively, were resistant to BCNU, but their resistance declined sharply following pretreatment with the MGMT inhibitor O6-benzylguanine (O6-BG). On the other hand, PANC-1 and MIAPaCa-2 could not be eradicated with N-methylnitrosourea (MNU) at concentrations as high as 2 mM, even when pretreated with O6-BG. These two lines were shown to be modified genetically in microsatellite sequences by MNU and are believed to have a defective mismatch repair system, which may explain their resistance to methylating agents. Failure of pancreatic tumors to respond to nitrosoureas is related to high levels of MGMT expression and in some cases to genomic instability. However, these tumors can be sensitized to chloroethylating drugs and eradicated following the elimination of MGMT activity by O6-BG or homologous MGMT inhibitors.

Adenocarcinoma↗