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PubMed1984

Cisplatin, doxorubicin, cyclophosphamide, lomustine, and vincristine (PACCO) in the treatment of non-small cell bronchogenic carcinoma.

A total of 43 patients with non-small cell carcinoma from a small preliminary trial and a larger in-house study were evaluated after treatment with cisplatin (50 mg/m2), doxorubicin (50 mg/m2), cyclophosphamide (300 mg/m2), and vincristine (1.4 mg/m2), all given iv on Day 1, and lomustine (50 mg/m2) given orally on Day 1. The response rate in the larger trial was 9%, with a 95% confidence interval of 2%-24%. For the combined group of all patients, median survival was 200 days, with a 95% confidence interval of 115-229 days. Hematologic toxicity and nausea and vomiting were moderate to severe and there were two treatment-related deaths. This combination drug regimen appears to have no advantages over other, less toxic regimens in the treatment of non-small cell bronchogenic carcinoma.

Aged↗
PubMed1983

Effect of pretreatment with phenobarbital or SKF 525A on the toxicity and antitumor activity of lomustine.

Previous investigations have shown that the combination of the conventional chemotherapeutic agent lomustine (CCNU) and the nitroimidazole radiation sensitizer misonidazole can lead to an improved therapeutic result. To study whether altered CCNU metabolism plays a role in this chemopotentiation, mice were treated with known modifiers of hepatic microsomal enzymes prior to CCNU exposure, and tumor response and systemic toxicity were assessed. KHT sarcoma-bearing C3H/HeJ mice were pretreated with either (a) five daily doses of phenobarbital (80 mg/kg) to induce the microsomal enzymes and then CCNU 48 hours later or (b) a 50-mg/kg dose of the microsomal enzyme inhibitor SKF 525A 1 hour before CCNU. Tumor response and normal tissue toxicity following treatment were measured using a regrowth delay and 30-day lethality assay, respectively. Phenobarbital pretreatment reduced both the antitumor efficacy and toxicity of CCNU (factor of approximately 0.8), while SKF 525A increased the effect of CCNU in both cases (factor of approximately 1.6). Thus, unlike pretreatments with the sensitizer misonidazole, pretreatments with phenobarbital or SKF 525A did not result in a therapeutic advantage for CCNU.

Animals↗
PubMed1993

The combined action of thiotepa and lomustine cytostatics, of estradiol hormone and of vitamins E and A on Walker tumor chromatin structure.

The combined action of thiotepa (1 mg) and lomustine (3 mg) cytostatics, of estradiol hormone (0.05 mg) and of vitamins E (1 mg) and A (56 U) on Walker tumor chromatin of Wistar rats, was analysed. The cytostatics used determine modifications at chromatin DNA level, with the decrease of intact double helix proportion, as indicated by the analysis of chromatin thermal transition and of fluorescence intensity of chromatin-ethidium bromide complexes. Also, the determination of chromatin tyrosine and tryptophane intrinsic fluorescence denotes a diminution of the quantity of basic and acidic chromatin proteins under these cytostatics. The association of cytostatics administration with a treatment with estradiol or with vitamins E and A, determines a complex and specific change in the parameters analysed. Generally, the modulation under vitamins action consists of an increase in double helix chromatin DNA proportion, and of chromatin acidic proteins quantity. In the combined treatment estradiol-cytostatics, an increase takes place in basic and acidic proteins quantity coupled with DNA.

Animals↗
PubMed1997

[Assessment of procarbazine, vincristine and lomustine association (PCV protocol) in oligodendroglioma and mixed glioma].

Effective chemotherapy using PCV (procarbazine, lomustine and vincristine) has been documented in anaplastic oligodendrogliomas and oligoastrocytomas. A pilot study using PCV was conducted for relapsing patients with anaplastic oligodendrogliomas and oligoastrocytomas. Preliminary results are reported. Fourteen patients were enrolled. All received at least two courses of PCV and were evaluable for response. Eleven patients (78%) responded to chemotherapy with complete responses in 2 patients. Response was more obvious regarding contrast enhanced areas than volumes changes (11 responses versus 7). A story of seizure was the main clinical prognostic factor for response. All toxicities were manageable and no treatment related death occurred. Chemotherapy is an effective treatment in aggressive oligodendrogliomas. Further studies must assess the role of chemotherapy in the multidisciplinary management of oligodendroglioma.

Adolescent↗
PubMedDate not supplied

Mitoxantrone, vinblastine, and lomustine (CCNU) (MVC): a highly active regimen for advanced and poor-prognosis Hodgkin's disease.

PURPOSE: A new regimen, MVC (mitoxantrone, vinblastine, and CCNU [lomustine]), was studied in advanced Hodgkin's disease. This regimen combines the most effective elements of previous regimens for poor-prognosis Hodgkin's disease and eliminates agents with unnecessary toxicities and marginal activity. Initially, patients with relapsed or refractory disease were entered, and after substantial activity was observed, patients with advanced-stage, newly diagnosed Hodgkin's disease were also treated. PATIENTS AND METHODS: Thirty-six relapsed or refractory patients were entered on this study. Prior treatment included radiotherapy alone (three patients), combined-modality treatment (n = 21), and single (n = 2) or multiple chemotherapy regimens (n = 10). Seventeen advanced-stage (bulky IIB-IVB) newly diagnosed Hodgkin's patients were also entered, with a median follow-up of 7 years. RESULTS: Thirty-two of 36 (88%) relapsed/refractory patients responded to MVC, with 18 partial responses (50%) and 14 complete responses (39%). Median complete response duration is 20 months (range, 2 to 108+ months). The median survival of all previously treated MVC patients is 28 months (range, 4 to 127+ months). Eleven of 32 previously treated MVC responders remain alive and disease-free at 12 to 127+ months, seven after autologous bone marrow transplantation (12 to 127+ months) and four after MVC without transplantation (31 to 113+ months). Thirteen of 17 advanced-stage, newly diagnosed Hodgkin's disease patients achieved a complete response and four achieved a partial response to MVC (100% response rate). Two complete response and all partial response patients have relapsed. Eight complete responses are ongoing at 11 to 114+ months. Three patients died in complete response at 11, 42, and 43 months. Median response duration has not been reached. DISCUSSION: MVC is a highly active regimen in relapsed and advanced-stage Hodgkin's disease, with outcome results comparable to other established regimens. Treatment is associated with myelosuppression but is otherwise well tolerated. MVC provides an effective alternative regimen for newly diagnosed patients with Hodgkin's disease and an effective salvage regimen for patients previously treated with anthracyclines.

Adult↗
PubMed1998

Dose-intensification of procarbazine, CCNU (lomustine), vincristine (PCV) with peripheral blood stem cell support in young patients with gliomas.

BACKGROUND: The regimen of procarbazine, CCNU, and vincristine is active against gliomas. Previous attempts at dose-intensification have been unsuccessful because of delayed and cumulative myelosuppression. We sought to determine whether peripheral blood stem cell (PBSC) infusions would allow dose-escalation and time compression. PROCEDURE: Eleven patients, age 2.8-35.9 years, with newly diagnosed (n = 10) or recurrent (n = 1) gliomas underwent PBSC harvesting after mobilization with G-CSF. Chemotherapy consisted of CCNU 130 mg/m2 on day 0, vincristine 1.5 mg/m2 on days 0 and 7, and procarbazine 150 mg/m2 on days 1-7. PBSCs were reinfused on day 9 of each course. Four courses of chemotherapy were administered 28 days apart or when counts recovered. Involved field radiation was administered to newly diagnosed high-grade glioma patients following recovery from chemotherapy. RESULTS: Compared to the standard PCV regimen given every 6 weeks, dose intensity received was 1.7- and 1.8-fold greater for CCNU and procarbazine. Chemotherapy was delivered on time in 33/41 (80.5%) courses. Four courses (9.8%) were complicated by absolute neutrophil counts < 200/microL; platelet nadirs < 50,000/microL occurred in two courses (4.9%). Fever with neutropenia complicated three courses. Eight of 9 patients with measurable disease had an objective decrease in tumor size and/or decreased enhancement. Median survival for patients with high-grade gliomas (n = 6) was 13 months. CONCLUSIONS: Dose-intensification of PCV is possible using PBSCs.

Adolescent↗
PubMed1988

Results of the treatment of children with recurrent gliomas with lomustine and vincristine.

Gliomas comprise over 50% of all childhood brain tumors. Treatment of recurrent childhood gliomas has been disappointing and the effectiveness of therapy has been difficult to judge because of the variable natural history of the disease. Information gathered recently has suggested that treatment with [1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea)] (CCNU) and vincristine (VCR) after radiotherapy is effective in prolonging survival in children with newly diagnosed anaplastic gliomas. The authors have used these same drugs--CCNU (100 mg/m2) and VCR (1.5 mg/m2 up to a maximum dose of 2 mg)--in 6-week cycles for a maximum of eight cycles in children with recurrent gliomas. To date, 15 patients have been treated; five patients had malignant gliomas and ten low-grade gliomas. Three children showed improvement, five had stable disease, and seven had progressive disease. Of the five patients with malignant gliomas, four progressed within two cycles of treatment and one had stable disease for 7 months on treatment and then relapsed. Seven of ten children with low-grade gliomas benefitted from treatment and six remain in continuous remission a median of 16 months after initiation of therapy. Three of these children are off all therapy 21, 30, and 30 months after treatment, respectively. Therapy was well tolerated and toxicity consisted primarily of reversible bone marrow suppression. The authors conclude that CCNU and VCR chemotherapy is effective in children with recurrent low-grade gliomas and can result in relatively long-term disease stabilization. In limited experience of the authors, it is not of benefit in children with recurrent anaplastic lesions.

Adolescent↗
PubMed1985

Clinical pharmacokinetics of oral CCNU (lomustine).

The plasma pharmacokinetics of orally administered CCNU (130 mg/m2) were studied in four patients using reversed-phase high-performance liquid chromatography (HPLC) analysis. Parent CCNU was not detected in the plasma of any of the patients, probably due to complete conversion to monohydroxylated metabolites during the 'first pass' through liver and gut. However, two monohydroxylated metabolites, trans-4-hydroxy CCNU and cis-4-hydroxy CCNU, were found at high concentrations, the relative amounts being about 6:4. Peak concentrations of the metabolites were reached 2-4 h after administration and were remarkably similar for all four patients, the total being 0.8-0.9 micrograms/ml. The metabolites were also detected in a tumour biopsy. Plasma clearance half-lives of the two metabolites were similar in each patient but showed a two-fold variation between patients, from 1.3 to 2.9 h. These results suggest that the antitumour activity and systemic toxicity of CCNU when given orally are due mainly to its monohydroxylated metabolites. Finally, comparison with data obtained in vitro and in mice showed that the nitrosourea exposures in these patients were at the lower limit of those required for significant antineoplastic activity.

Administration, Oral↗
PubMed2006

Effects of lipid association on lomustine (CCNU) administered intracerebrally to syngeneic 36B-10 rat brain tumors.

A syngeneic, intracerebral rat brain tumor model was developed and characterized and then used to evaluate the therapeutic enhancement of lipid-associated 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). The Fisher rat glioma cell 36B-10 (100,000-500,000 cells) was implanted intracranially to Fisher F-344 rats into the caudate nucleus. Animals treated with lipid-associated CCNU showed a 2- to 10-fold decrease in tumor size compared with animals treated with free CCNU, indicating that lipid association increases the therapeutic index of intracerebral CCNU treatment. Moreover, the syngeneic rat brain tumor model may be useful for evaluation of other therapeutic modalities.

Alkylating Agents↗
PubMed1984

Karyometric, cytophotometric, and histoenzymatic studies on neuroglia of young rats subjected to CCNU (Lomustine) action.

Studies on the effects of CCNU on neuroglia cells of the central nervous system in young individuals were conducted on 19 Wistar strain rats, each given 2 mg doses of 0.25 CCNU in 7th and 12th d of life. Karyometric and cytophotometric studies proved that CCNU administered to young rats induced changes in oligodendroglia and astroglia of the central nervous system. The changes included significant increase in nuclei contour and in the area of nuclei cross-section in oligodendro- and astroglia cells, elongation of oligodendroglia nuclei and an augmented DNA content in the 2 neuroglia types. The observed karyometric and cytophotometric changes were more evident in oligodendroglia nuclei than in astroglia nuclei.

Alkaline Phosphatase↗