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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↗
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↗
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↗
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↗
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↗
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↗
PubMed1980

Biodistribution of 14C-lomustine in an animal tumor model.

A formulation of 14C-lomustine in propylene glycol-ethanol (4:1) was administered intravenously to rats infiltrated with glioma tumors of the astrocytic series (RT6). The organ and tumor distribution of this agent was followed at 1, 4, 12, and 24 hr. Rapid blood disappearance (0-1 hr) of the label concomitant with an increase in all organs except the lung, muscle, and brain was observed. Only the blood, liver, and muscle contained greater than 1% of the dose after 24 hr. The bladder, liver, small bowel, and kidneys concentrated the highest percentages throughout the study. The distribution of 14C-lomustine in the tumor relative to the brain, muscle, and blood showed a maximum 4-12 hr after administration.

Animals↗
PubMed1997

Chemoimmunotherapy with bleomycin, vincristine, lomustine, dacarbazine (BOLD) plus interferon alpha for metastatic melanoma: a multicentre phase II study.

High response rates in patients with metastatic melanoma have been achieved with combination chemoimmunotherapy. A response rate of 62% in 45 patients has been reported for treatment with dacarbazine, bleomycin, vincristine, lomustine (BOLD) plus interferon alpha (IFN-alpha). We conducted a multicentre phase II study to confirm these results. Melanoma patients with distant metastases were treated as outpatients with dacarbazine 200 mg m(-2) on days 1-5, vincristine 1 mg m(-2) on days 1 and 4, bleomycin 15 mg on days 2 and 5 i.v. and lomustine 80 mg orally on day 1, repeated every 4 weeks. IFN-alpha-2b was initiated s.c. on day 8 at 3 MU daily for 6 weeks, and 6 MU t.i.w. thereafter. Forty-three patients entered the study. The median number of metastatic sites was three (range 1-5), and 81% of patients had visceral metastases. Nine patients had brain metastases, and seven patients were systemically pretreated. Among the 41 patients that were evaluable for response, the response rate was 27% (95% CI 14-3%), with one complete and ten partial remissions. The response rate in 25 previously untreated patients without brain metastases was 40% (95% CI 21-61%). Median duration of response was 6 (range 2-14+) months; median overall survival was 5 (1-26) months. The main toxicity was malaise/fatigue. We confirm that BOLD plus IFN-alpha has activity in metastatic melanoma. The lower response rate in our study compared with the previous report is probably related to patient selection, as in the previous study 46% of patients had stage III disease, whereas all our patients had stage IV disease, which is associated with a worse prognosis.

Abdominal Neoplasms↗
PubMed1995

Quality versus quantity of life in the treatment of patients with advanced small-cell lung cancer? A randomized phase III comparison of weekly carboplatin and teniposide versus cisplatin, adriamycin, etoposide alternating with cyclophosphamide, methotrexate, vincristine and lomustine. Swiss Group for Clinical Cancer Research (SAKK).

BACKGROUND: Based on a promising pilot study with weekly carboplatin and teniposide (CBDCA/VM) the Swiss Group for Clinical Cancer Research (SAKK) performed a randomised phase III trial in patients with extensive-disease small-cell lung cancer aimed at the development of an effective palliative treatment with low subjective toxicity. PATIENTS AND METHODS: From September 1989 to September 1991 patients were randomised to a weekly regimen of CBDCA/VM or to our 'standard chemotherapy' of cisplatin, adriamycin and etoposide alternating with cyclophosphamide, methotrexate, vincristine and lomustine (PAV-CyMOC). RESULTS: The trial was closed before the planned accrual of 140 evaluable patients due to a significant survival difference shown by an interim analysis. Of the 61 patients 59 were eligible and included in the final analysis. The results achieved with the PAV-CyMOC regimen were significantly better than those observed in patients treated with weekly CBDCA/VM (remission rate of 65% vs. 29%; p = 0.006). The median survival of patients treated with the PAV-CyMOC combination was significantly longer than that of patients receiving weekly CBDCA/VM (260 days vs. 147 days; p = 0.0035). The 1-year survival rate was 30% in the PAV-CyMOC arm compared to 4% in the CBDCA/VM-treated patients. As expected, side effects including myelosuppression, alopecia and mucositis were significantly more pronounced in patients treated with the PAV-CyMOC regimen. No significant difference was found in patient-rated tumor symptoms and general quality-of-life categories. CONCLUSION: Contrary to our initial expectation that we would achieve similar therapeutic results with less subjective toxicity, in this randomised prospective trial the results achieved by weekly carboplatin and teniposide were significantly inferior in terms of remission rate and survival to those of our 'standard regimen' of cisplatin, adriamycin and etoposide alternating with cyclophosphamide, methotrexate, vincristine and lomustine. The weekly regimen was less toxic than the standard chemotherapy. Whether patients are willing to accept a significant trade-off between quantity and quality of life remains to be evaluated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Attempted prevention of blast crisis in chronic myeloid leukemia by the use of pulsed doses of cytarabine and lomustine. A Cancer and Leukemia Group B study.

An attempt to prevent the blast crisis in chronic myeloid leukemia by the use of pulsed doses of (cytarabine cytosine arabinoside) and lomustine was attempted as a cooperative group study by Cancer and Leukemia Group B. The basis for this study was to delay the development of blast crisis by pulsing dose of drugs known to be effective against emerging "blast" cells. The experimental arm which consisted of cytarabine and lomustine did not produce overall results superior to conventional treatment with busulfan. This was related to the non-hematologic effects of the combination which produced significant gastrointestinal toxicity leading to relatively early discontinuation of the combination. Nevertheless, the trial design allowed relatively prompt discontinuation of experimental arm and cross-over to conventional treatment with either hydrea or busulfan. No evidence existed that the use of new drug combinations in CML prejudiced the patient's chance to response to conventional chemotherapy. Thus, a role model for future trials in this disease was developed. With the development of the interferons and other experimental forms of therapy this conceptual development may be of significance.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1979

Quality and duration of survival in glioblastoma multiforme. Combined surgical, radiation, and lomustine therapy.

A retrospective evaluation of the quality and length of survival of 74 patients nonrandomly receiving lomustine, 100 to 110 mg/sq m, following craniotomy and irradiation for glioblastoma multiforme was performed. After surgery all patients were capable of at least partial self-care. Patients receiving postoperative irradiation and lomustine had a median survival of 11.5 months. While receiving chemotherapy, 40% of these patients were capable of at least partial employment; 75% were able to care for themselves. These levels of function were stable for 70% of the average postoperative course (8.0 months), following which a decline ensued.

Activities of Daily Living↗
PubMed1986

Treatment of advanced resistant Hodgkin's disease with lomustine, etoposide, and prednimustine.

Fifteen patients with Hodgkin's disease resistant to the chemotherapy combinations of cyclophosphamide, vinblastine, procarbazine and prednisone and doxorubicin, bleomycin, vinblastine, and dacarbazine were treated with lomustine, etoposide, and prednimustine. Four of them achieved complete remission and two achieved partial remission (overall response rate, 40%). The median duration of response was 5.5 months, with two complete responders relapsing at 4 and 17 months and the other two remaining disease-free at 7 and 18 months, whereas disease progression was observed at 2.5 and 6 months in the partial responders. Extrahematological toxicity was scarce. Severe myelosuppression was observed in only three patients. These results indicate that lomustine, etoposide, and prednimustine can play a role in the treatment of advanced resistant Hodgkin's disease.

Adolescent↗
PubMed1977

Combination chemotherapy with doxorubicin and lomustine. Treatment of refractory Hodgkin's disease.

Ten patients with advanced Hodgkin's disease refractory to combination therapy with nitrogen mustard, vincristine sulfate, procarbazine, and prednisone (MOPP) were treated with a combination of doxorubicin hydrochloride and lomustine. Toxicity was acceptable. Five patients (50%)attained complete remission (median duration, 15 months). Three patients attained a partial remission (median duration, four months). Survival ranged from three to more than 40 months, and five patients are still alive. One patient remains disease-free after a course of radiation therapy to a site of localized nodal relapse. The doxorubicin-lomustine regimen has induced meaningful remissions in a patient population with very refractory disease.

Administration, Oral↗
PubMed1988

Bleomycin, vincristine, lomustine, and DTIC chemotherapy for metastatic melanoma.

Forty-six consecutive, evaluable patients with a diagnosis of metastatic melanoma without prior chemotherapy were treated with bleomycin, vincristine, lomustine, and DTIC (BOLD). Treatment was repeated every 28 days for two cycles. Complete restaging then was performed, and response to treatment was determined. Of the 46 patients, five (11%) achieved a complete response, five (11%) achieved a partial response, nine (19%) obtained disease stabilization, and 27 (59%) had progressive disease. If four patients who died of rapidly progressive disease are included, the response rate drops to 20%. Overall median survival was 6 months. These results are inferior to the 40% and 46% response rates reported by other investigators. The modest response rate toxicity and expense of the regimen do not support its use in metastatic melanoma except, perhaps, in selected patients with soft tissue and/or lung metastasis.

Antineoplastic Combined Chemotherapy Protocols↗