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At least 19 recordsLinked to original sources
PubMed1986

Cytotoxic chemotherapy of disseminated cutaneous malignant melanoma--a prospective and randomized clinical trial of procarbazine, vindesine and lomustine versus procarbazine, DTIC and lomustine.

Forty-three patients with measurable disseminated cutaneous malignant melanoma, stages III-IV, and without previous cytotoxic chemotherapy or immunotherapy, were randomly allocated from 30 June 1980 to 30 November 1984, to receive either a schedule of procarbazine (100 mg/m2 p.o., max 150 mg) days 1-10, vindesine (3 mg/m2 i.v., max 5 mg) days 1 and 8, and CCNU (150 mg/m2 p.o., max 200 mg) day 1, (regimen A), with 4-6 weeks interval between the courses, or a combination of procarbazine (100 mg/m2 p.o., max 150 mg) days 1-10, DTIC (250 mg/m2 i.v. max 400 mg) days 1-5, and CCNU (150 mg/m2 p.o. max 200 mg) day 1 (regimen B), also repeated every 4-6 weeks. Twenty-one patients were treated according to regimen A and 22, by regimen B. Objective responses (three PR, two CR) were seen in 5 out of 21 patients (23.8%) in group A and 8 out of 22 (four PR, four CR), (36%) in the group B, this difference not being statistically significant. The median duration of response was 8 and 10 months, respectively, and the estimated median survival 10 months for regimen A and 14 months for regimen B. Regimens A and B must be regarded as of no value in view of poor response rate and the unacceptable toxicity, respectively. Therefore, we are now conducting a further phase II study, to determine, prospectively, whether the previously noted high response rate obtained with our previous POC protocol can be reaffirmed.

Adult↗
PubMed1995

Multiorgan failure associated with lomustine overdose.

OBJECTIVE: To report a lomustine overdose in a patient with anaplastic astrocytoma. CASE SUMMARY: A 28-year-old woman with anaplastic astrocytoma was treated with partial resection and radiation therapy followed by a lomustine-containing regimen. The patient took lomustine 1400 mg po over a week, her regular dose being 200 mg on day 1 of the regimen. Pancytopenia developed within a week after the last dose of lomustine and the patient was admitted to the bone marrow transplant unit for supportive care. About 3 weeks later, the patient gradually developed a multiorgan dysfunction, including liver, brain, and lungs without evidence of infection or tumor progression, and died on day 45 of hospitalization. DISCUSSION: This is the third reported case of lomustine overdose that resulted from supplying the patient with more tablets than needed for 1 dose. Although late hematopoietic recovery may be possible after such a high dose of lomustine, other organ toxicities might be detrimental. CONCLUSIONS: Physicians and pharmacists should avoid supplying more tablets than needed for 1 lomustine dose. High doses of lomustine may cause irreversible multiorgan toxicities.

Adult↗
PubMed1991

Nitrosoureas lomustine, carmustine and fotemustine induced hepatotoxic perturbations in rats: biochemical, morphological and flow cytometry studies.

Chloroethylnitrosoureas are reactive compounds that are highly effective against malignant neoplasms in humans and animals. The most widely used nitrosoureas, lomustine and carmustine, are known to be hepatotoxic and to induce pericholangitis and intrahepatic cholestasis, which in the long term lead to cholangiolysis and biliary cirrhosis. However, the nitrosourea fotemustine has proved to be non-hepatotoxic at 20 mg/kg and 50 mg/kg. We have studied the effect of these three nitrosoureas on the cytotoxicity and cellular kinetics of rat liver cells. Lomustine and carmustine modify the proliferation index of liver cells in vivo: flow cytofluorometry showed that DNA cell distribution is quite similar for lomustine and carmustine, with subsequent accumulation of cells in G2 + M phase. 3 months later regressive morphological and cell cycle perturbations are noted for the lower dose of lomustine and carmustine. The most severe lesions are noted with lomustine (50 mg/kg). Fotemustine is not hepatotoxic and preferentially induces S phase perturbations. The more toxic nitrosoureas, lomustine and carmustine, induce comparable hepatocyte cell cycle alterations which differ from those induced by the less hepatotoxic nitrosourea fotemustine.

Alkaline Phosphatase↗
PubMed2000

Effects of carmustine and lomustine on arylamine N-acetyltransferase activity and 2-aminofluorene-DNA adducts in rat glial tumor cells.

Carmustine and lomustine are nitrosourea antitumor chemotherapeutic agents which were used to determine whether or not they could affect arylamine N-acetyltransferase (NAT) activity and DNA-2-aminofluorene adducts in rat glial tumor cell line (C6 glioma). The NAT activity was measured by high preformance liquid chromatography (HPLC) assaying for the amounts of N-acetyl-2-aminofluorene (AAF) and N-acetyl-p-aminobenzoic acid (N-Ac-PABA) and remaining 2-aminofluorene (AF) and p-aminobenzoic acid (PABA). The results indicate that NAT activity in glial tumor cell cytosols and intact tumor cells were decreased by carmustine and lomustine in a dose-dependent manner. The apparent values of Km and Vmax of NAT from rat glial tumor cell also decreased after co-treatment of carmustine and lomustine in both examined cytosols and intact cells. Following exposure of glial tumor cells to the various concentrations of AF with or without co-treatment with carmustine and lomustine, DNA-AF adducts were determined by using gamma-[32p]-dATP and HPLC. The DNA-AF adducts in rat glial tumor cells were decreased by co-treatment with carmustine and lomustine. This report is the first demonstration to show carmustine and lomustine did inhibit rat glial tumor cells NAT activity and DNA-AF adduct formation.

Animals↗
PubMed2006

A phase I/II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma.

Temozolomide is an alkylating agent with activity in the treatment of melanoma metastatic to the brain. Lomustine is a nitrosurea that crosses the blood brain barrier and there is evidence to suggest that temozolomide may reverse resistance to lomustine. A multicentre phase I/II study was conducted to assess the maximum-tolerated dose (MTD), safety and efficacy of the combination of temozolomide and lomustine in melanoma metastatic to the brain. Increasing doses of temozolomide and lomustine were administered in phase I of the study to determine the MTD. Patients were treated at the MTD in phase II of the study to six cycles, disease progression or unacceptable toxicity. Twenty-six patients were enrolled in the study. In phase I of the study, the MTD was defined as temozolomide 150 mg m(-2) days 1-5 every 28 days and lomustine 60 mg m(-2) on day 5 every 56 days. Dose-limiting neutropaenia and thrombocytopaenia were observed at higher doses. Twenty patients were treated at this dose in phase II of the study. No responses to therapy were observed. Median survival from starting chemotherapy was 2 months. The combination of temozolomide and lomustine in patients with brain metastases from melanoma does not demonstrate activity. The further evaluation of this combination therefore is not warranted.

Administration, Oral↗
PubMed1996

Combination of 6-thioguanine, procarbazine, lomustine, and hydroxyurea for patients with recurrent malignant gliomas.

OBJECTIVE: To determine the efficacy of the combination of 6-thioguanine, procarbazine, lomustine, and hydroxyurea for patients with recurrent malignant gliomas after failure of either previous radiotherapy alone or previous radiotherapy plus nitrosourea-based chemotherapy. METHODS: Seventy-seven patients with recurrent malignant gliomas were studied. 6-Thioguanine was administered for 4 days before lomustine, and procarbazine was administered for 1 day before and 2 days after lomustine to potentiate lomustine's antitumor effect. Hydroxyurea was initiated 1 day before lomustine and continued for a total of 3 days. RESULTS: Thirty patients with glioblastomas and 47 patients with anaplastic gliomas were eligible for evaluation. In the glioblastoma group, 2 of 30 patients had a partial response and 8 of 30 patients had stable disease. This group of patients who responded and had stable disease included 6 of 10 patients who had not undergone previous chemotherapy but only 4 of 20 who had undergone previous chemotherapy. The overall median time to disease progression for the glioblastoma group was 9 weeks. In the anaplastic glioma group, 11 of 47 patients had a partial response and 25 of 47 had stable disease, including 23 of 30 without previous chemotherapy and 13 of 17 who had undergone previous chemotherapy. The median time to disease progression for the whole anaplastic glioma group was 24 weeks; however, the time to disease progression was 50 weeks for responding patients who had not undergone previous chemotherapy and 25 weeks for those who had undergone previous chemotherapy. CONCLUSION: Our results indicate that chemotherapy with a combination of 6-thioguanine, procarbazine, lomustine, and hydroxyurea is active for patients with recurrent anaplastic gliomas and glioblastomas not previously treated with nitrosourea-based chemotherapy but is inactive for patients with glioblastomas previously treated with chemotherapy.

Adolescent↗
PubMed1995

Randomized phase III study of 5-fluorouracil plus high dose folinic acid versus 5-fluorouracil plus folinic acid plus methyl-lomustine for patients with advanced colorectal cancer.

BACKGROUND: Metastatic colorectal cancer is generally incurable. The most active regimen available, 5-fluorouracil (5-FU) and folinic acid (Leucovorin), produces response rates of approximately 25% to 30%. Methyl-lomustine is a nitrosourea with modest activity against colorectal cancer. A randomized trial was undertaken to evaluate the impact the addition of methyl-lomustine would have on response, duration of survival, and survival rates in patients with advanced colorectal cancer. METHODS: The methyl-lomustine/5-FU/Leucovorin (MFL) regimen consisted of methyl-lomustine (110 mg/m2), administered on Day 1 of each 8-week cycle with six weekly boluses of 5-FU (600 mg/m2), and Leucovorin (500 mg/m2). The FL treatment arm consisted of the administration of 5-FU and Leucovorin as described above. Patients were evaluated for response and toxicity after each 8-week cycle. RESULTS: Of 319 patients included in this trial, 297 (93.1%) had disease evaluable for response and toxicity: 145 received MFL, and 152 received FL. In this trial, 526 courses of MFL and 529 courses of FL were administered. Methyl-lomustine/5-FU/Leucovorin treatment resulted in 4 complete and 30 partial responses (response rate, 21.9%), and FL treatment resulted in 9 complete and 33 partial responses (response rate, 26.4%). There was no significant difference in median survival duration between patients in the two arms (MFL = 48 weeks, FL = 51 weeks). However, MFL was significantly more toxic with greater myelosuppression than was FL (Grade 3-4 neutropenia: MFL = 56 patients, FL = 27 patients, P < 0.001; Grade 3-4 thrombocytopenia: MFL = 49 patients, FL = 2 patients, P < 0.001; Grade 3-4 anemia: MFL = 15 patients, FL = 6 patients, P < 0.001; and more prolonged median duration of granulocytopenia: MFL = 9 days, FL = 7 days, P < 0.001; and thrombocytopenia: MFL = 14 days, FL = 7.5 days, P < 0.001). CONCLUSION: Because the addition of methyl-lomustine in the MFL schedule markedly increased the toxicity of the regimen and because the FL regimen was as effective as MFL, the authors recommend that Leucovorin and 5-FU remain the treatment choice for treating patients with metastatic colorectal cancer.

Adult↗
PubMed2006

Phase II trial of lomustine plus temozolomide chemotherapy in addition to radiotherapy in newly diagnosed glioblastoma: UKT-03.

PURPOSE: To evaluate toxicity and efficacy of the combination of lomustine, temozolomide (TMZ) and involved-field radiotherapy in patients with newly diagnosed glioblastoma (GBM). PATIENTS AND METHODS: Thirty-one adult patients (median Karnofsky performance score 90; median age, 51 years) accrued in two centers received involved-field radiotherapy (60 Gy in 2-Gy fractions) and chemotherapy with lomustine 100 mg/m2 (day 1) and TMZ 100 mg/m2/d (days 2 to 6) with individual dose adjustments according to hematologic toxicity. RESULTS: A median of five courses (range, one to six courses) were delivered. WHO grade 4 hematotoxicity was observed in five patients (16%) and one of these patients died as a result of septicemia. Nonhematologic toxicity included one patient with WHO grade 4 drug-induced hepatitis (leading to discontinuation of lomustine and TMZ) and one patient with WHO grade 2 lung fibrosis (leading to discontinuation of lomustine). The progression-free survival (PFS) rate at 6 months was 61.3%. The median PFS was 9 months (95% CI, 5.3 to 11.7 months), the median overall survival time (MST) was 22.6 months (95% CI, 12.5 to not assessable), the 2-year survival rate was 44.7%. O6-methylguanine-DNA methyltransferase (MGMT) gene-promoter methylation in the tumor tissue was associated with longer PFS (P = .014, log-rank test) and MST (P = .037). CONCLUSION: The combination of lomustine, TMZ, and radiotherapy had acceptable toxicity and yielded promising survival data in patients with newly diagnosed GBM. MGMT gene-promoter methylation was a strong predictor of survival.

Administration, Oral↗
PubMedDate not supplied

Hematological toxicity and therapeutic efficacy of lomustine in 20 tumor-bearing cats: critical assessment of a practical dosing regimen.

Twenty cats with spontaneously arising tumors received oral lomustine at a dose range of 32 to 59 mg/m2 every 21 days. Due to biohazard concerns associated with lomustine capsule reformulation, a standardized 10-mg capsule dosage was used for all cats regardless of body weight. Severe hematological toxicity was infrequent, with the incidence of either grade III or IV neutropenia and thrombocytopenia being 4.1% and 1.0%, respectively. Cats receiving higher cumulative doses of lomustine trended toward a greater likelihood for progressive neutropenia (P=0.07). Two cats with lymphoma, two cats with fibrosarcoma, and one cat with multiple myeloma achieved a measurable partial response to lomustine therapy. Cats treated with higher dosages of lomustine trended toward statistically significant higher response rates (P=0.07).

Administration, Oral↗
PubMed1985

Nephrotoxicity of lomustine. A case report and literature review.

A patient is presented who developed nephrotoxicity after therapy with lomustine (CCNU) for astrocytoma of the brain. Only three other cases of lomustine nephrotoxicity have been reported, and all cases have been associated with cumulative drug doses of greater than 1,500 mg/m2. The clinical and pathologic features of lomustine nephrotoxicity are reviewed. It is recommended that cumulative doses of more than 1,200-1,4000 mg/m2 lomustine be avoided because of the risk of nephrotoxicity.

Adult↗
PubMedDate not supplied

Overdose of lomustine: report of two cases.

Two male patients with high-grade gliomas were treated with subtotal or total resection and radiotherapy followed by a lomustine-containing chemotherapy regimen. Both patients took lomustine at an oral dose of 800 mg over five days instead of their regular doses of 200 and 240 mg. Grade 4 neutropenia and thrombocytopenia developed in both patients within two weeks of the last lomustine dose. One of them was admitted to hospital because of febrile neutropenia. Neutropenia and thrombocytopenia were detected in the other patient when he was examined in the emergency room following a generalized convulsion. Both patients recovered from the severe myelosuppression caused by lomustine. No other organ toxicities were observed.

Adult↗
PubMed1994

A phase I trial of weekly lomustine in patients with advanced cancer.

BACKGROUND: Lomustine is a commercially available chloroethyl nitrosourea compound whose antitumor activity in vitro and in animal tumor models exceeds its activity in humans. Part of the poor clinical performance of this drug may be explained by dose-limiting subjective toxicity observed with the standard schedule of one oral dose of approximately 130 mg/m2 every 6-8 weeks. METHODS: Twenty patients were enrolled in a Phase I clinical trial of weekly oral lomustine. The first dose level was 24 mg/m2, with subsequent dose increases in increments of 6 mg/m2. Intrapatient dose escalations were allowed if there were no toxic reactions noted after 12 weekly doses. RESULTS: The dose-limiting toxic effect was the development of thrombocytopenia in 35% of patients (6 of 17) treated at 30 mg/m2 after a median of 12 weekly doses (range, 5-20 weeks), whereas in 18% of patients (3 of 17), neutropenia developed after a median of 12 weeks (range, 9-22 weeks). Grade 3 or Grade 4 hematologic toxicity developed in three of three patients whose doses were escalated to 36 mg/m2/week after showing no evidence of toxicity for 12-16 weeks at 30 mg/m2/week. Partial remission was observed in two patients with malignant melanoma, and stable disease was observed in two patients with hypernephroma. Nausea, vomiting, and malaise were not significant complications of treatment. CONCLUSION: Lomustine can be administered at a dose of 30 mg/m2/week for 12+ weeks to patients with cancer who have received previous treatment with minimal toxicity while retaining antitumor activity.

Administration, Oral↗
PubMed2000

Chemosensitivity in childhood brain tumours in vitro: evidence of differential sensitivity to lomustine (CCNU) and vincristine.

The aim of this study was to examine the range of sensitivity of a panel of short-term cultures derived from different types of malignant childhood brain tumours including medulloblastoma, ependymoma and glioblastoma multiforme to three cytotoxic drugs, lomustine (CCNU), vincristine (VCR) and procarbazine (PCB). Sensitivity was assessed using a modification of the dimethylthiazolyl-2,5-diphenyl tetrazolium bromide (MTT) assay. Short-term cell lines derived from ependymomas were considerably more resistant to VCR than other types of childhood brain tumours, while cultures derived from supratentorial primitive neuroectodermal tumour (PNET) displayed marked sensitivity to both lomustine and VCR. Cultures from ependymomas, medulloblastoma and astrocytic gliomas had similar sensitivity to lomustine and PCB as cultures derived from adult malignant astrocytoma.

Adult↗
PubMed1986

Lomustine (CCNU)-induced pulmonary fibrosis.

A case of progressive pulmonary interstitial fibrosis following adjuvant lomustine (CCNU)-5-fluorouracil therapy for a colon carcinoma is reported. A close relationship between lomustine assumption and lung damage seems to emerge from the clinical, radiologic and histologic findings presented. On the basis of this experience and previous available data from literature, pulmonary toxicity must be regarded as a possible adverse effect of lomustine therapy.

Adult↗
PubMedDate not supplied

[Results of hyperfractionated radiation therapy used in combination with lomustin in malignant gliomas of the brain].

The postoperative use of lomustin, a nitrosourea agent, was investigated for its impact on the efficiency of hyperfractionated radiation therapy performed in patients with glioblastoma and anaplastic astrocytoma of the brain. A total of 35 patients (26 and 9 patients with glioblastoma and anaplastic astrocytoma, respectively) were followed up. Radiation therapy was performed, by using a total focal dose of 65 Gy in 2 steps or a single dose of 1.25 Gy twice daily every 4-6 hours. The patients received lomustin in a single oral dose of 160-200 mg at each of 2 stages of a hyperfractionated course of radiation therapy. The interval between two successive administrations was 5 weeks. Lomustin in combination with hyperfractionated radiation therapy was found to have no effect on the survival of patients with glioblastoma and anaplastic astrocytoma.

Adult↗
PubMed1987

Effect of lomustin on some platelet functions in vitro.

The effect of lomustin on platelet functions was investigated in vitro using a wide battery of tests. Lomustin was found to act as a specific inhibitor of platelet aggregation, release reaction and clot retraction and to induce acquired thrombocytopathy. Thus, impairment of platelet functions might play a role in hemorrhagic complications accompanying lomustin therapy in some cases.

Adenosine Diphosphate↗
PubMed2002

Chemoimmunotherapy with bleomycin, vincristine, lomustine, dacarbazine (BOLD), and human leukocyte interferon for metastatic uveal melanoma.

BACKGROUND: A Phase II trial comprising patients with metastatic uveal melanoma (Stage IVB) was undertaken to determine the activity of bleomycin, vincristine, lomustine, and dacarbazine (BOLD) chemotherapy with human leukocyte interferon, as well as the progression-free and overall survival of the patients according to the substage before treatment. METHODS: Twenty-two patients with histologically proven metastatic uveal melanoma received 15 mg of bleomycin (Days 2 and 5), 1 mg/m(2) vincristine (Days 1 and 4), 200 mg/m(2) dacarbazine (Days 1 to 5), and 80 mg lomustine (Day 1) every 4 weeks together with a leukocyte interferon preparation (3 x 10(6) IU daily for 6 weeks followed by 6 x 10(6) IU three times per week). RESULTS: Of 20 evaluable patients, 3 (15%; 95% confidence interval [CI] 0-38) obtained a partial objective response in hepatic and extrahepatic sites and 11 (55%; 95% CI 32-77) showed stable disease after receiving more than two cycles. The median progression-free survival was 4 months (95% CI 2-10) and the median overall survival was 12 months (95% CI 8-22). Eleven patients who had favorable pretreatment characteristics (Stage IVBa) survived a median of 17 months (95% CI 4-37) whereas 10 patients with less favorable characteristics (Stage IVBb) survived a median of 11 months (95% CI 1-23). Moderate toxicity occurred with this outpatient regimen. CONCLUSIONS: The BOLD/human leukocyte interferon regimen had modest activity against metastatic uveal melanoma in hepatic and extrahepatic sites. The median overall survival approached that reported for more aggressive intrahepatic therapy regimens. Substage differences can significantly impact study outcomes. Therefore, substage information should be reported to facilitate comparisons between studies.

Administration, Oral↗