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 181 records · Page 10Linked to original sources
PubMed1997

BOLD+interferon in the treatment of metastatic uveal melanoma: first report of active systemic therapy.

We conducted a phase II trial of bleomycin+vincristine+lomustine+dacarbazine (BOLD) with intercycle alpha interferon-2b in previously untreated patients with metastatic uveal melanoma. Objective tumor response and toxicity were assessed. Twenty-three patients with histologically verified metastatic uveal melanoma were enrolled into this study between November 1992 and August 1995. Chemotherapy was administered in the following fashion: dacarbazine (DTIC), 200 mg/m2 intravenously on days 1-5; vincristine, 1 mg/m2 (not to exceed 2 mg) intravenously on days 1 and 4; bleomycin, 15 mg intravenously on days 2 and 5; lomustine (CCNU), 80 mg orally on day 1; and alpha interferon-2b, 3 x 10(6) IU subcutaneously on days 8, 10, 12, 15, 17, 19. A cycle was 28 days, and patients were reevaluated after every 2 cycles. Among twenty evaluable patients, four objective responses were observed (RR = 20%). Hematologic toxicity was modest by comparison to some other combination chemotherapy regimens in common use. Neurotoxicity was frequently observed, but it was seldom severe. An unexpected and unpredictable severe pulmonary toxicity was observed in 3 patients, the etiology of which remains unclear. The regimen of BOLD+interferon is active in the treatment of metastatic uveal melanoma. The precise role of the regimen has to be defined in light of its toxicity, particularly the unpredictable pulmonary toxicity. The pattern of occurrence of these pulmonary events is most consistent with either an acquired hypersensitivity reaction or a cumulative toxic effect of 2 or more of the agents. Patients considered for treatment with this regimen must be judiciously selected. Those with no clear contraindications may benefit from a trial of this regimen, but they must be monitored closely.

Adult↗
PubMedDate not supplied

Comparison of the induction of SOS repair in Escherichia coli PQ37 and PQ243 by antineoplastic agents.

Six alkylating antineoplastic drugs (Cyclophosphamide, Chlorambacil, Busulfan, Melphalan. Streptozotocin and Lomustine) and two reference compounds (methyl methanesulphonate and N-methyl-N'-nitro-N-nitrosoguanidine) were investigated in the SOS Chromotest using the Escherichia coli strain PQ37 (wilde-type) and derived strain (PQ243), which carries the same markers as PQ37 and additionally tagA alkA. As a measure of the SOS induced activity induction factors of sflA::lacZ expression were determined. The strain PQ243 was more sensitive towards all compounds inducing SOS DNA repair then the strain PQ37 Cyclophosphamide was detected as negative in the strain PQ243 in the presence of an exogenous metabolic activation system. Lomustine was inactive both in the mutant strain and in the wild-type strain in the presence of S9 mix fraction as well as in the absence of it. Melphalan and Busulfan (without or with S9 mix) were shown to be positive exclusively in the strain PQ243. Based on these results, we discuss the usefulness of the strain PQ243 in the monitoring of the genotoxicity of drugs and in the genetic analysis of their mode of action.

Antineoplastic Agents, Alkylating↗
PubMed1988

Combination chemotherapy for advanced adenocarcinoma of the lung. A review.

Combination chemotherapy has been used widely in the treatment of inoperable adenocarcinoma of the lung (ACL), but without uniform success. This review summarizes current knowledge of combination chemotherapy in ACL, with the aim of establishing critical background material for future studies. Not all the numerous combinations applied in non-randomized studies have produced response rates above 20% when evaluated in randomized trials. This holds true for the following regimens: cyclophosphamide + lomustine + methotrexate (response rates 14%-38%), hexamethylmelamine + doxorubicin + methotrexate (13%-32%), methotrexate + doxorubicin + cyclophosphamide + lomustine (13%-24%), cyclophosphamide + doxorubicin + cisplatin (0-36%), cyclophosphamide + bleomycin + cisplatin (20%), mitomycin C + vinblastine + cisplatin (26%-33%), cyclophosphamide + doxorubicin + etoposide + cisplatin (29%) and vindesine + cisplatin (33%). None of these combinations has been shown to be clearly superior to single-agent treatment. Nor has any specific regimen been shown to have clear advantages over other active combination chemotherapy regimens or over the sequential administration of either single agents or combined treatments. The prognosis for patients with inoperable ACL remains dismal. None of the studies considered in this review revealed median survival times exceeding 47 weeks. High priority should therefore be given to the identification of new compounds with significant activity against ACL.

Adenocarcinoma↗
PubMed2004

Human osteosarcoma xenografts and their sensitivity to chemotherapy.

Despite the increased survival rates of osteosarcoma patients attributed to adjuvant chemotherapy, at least one third of the patients still die due to their disease. Further improvements in the management of osteosarcoma may rely on a more individualised treatment strategy, as well as on the introduction of new drugs. To aid in the preclinical evaluation of new candidate substances against osteosarcoma, we have established 11 human osteosarcoma xenograft lines and characterised them with regard to response to five different reference drugs. Doxorubicin, cisplatin methotrexate, ifosfamide and lomustine were effective in 3/11, 3/11, 1/10, 5/11 and 4/11 of the xenografts, respectively. Five xenografts were resistant to all compounds tested. We also assessed the mRNA expression levels of the xenografts for the O(6)-Methylguanine DNA Methyltransferase (MGMT), DNA topoisomerase II- (Topo II)-alpha, Gluthathione-S-transferase (GST)-pi, Multidrug-resistance related protein (MRP) 1 and Multidrug-resistance (MDR) 1 genes. There was an inverse correlation between the transcript levels of GST-pi and doxorubicin growth inhibition (r=-0.66; p<0.05), and between the transcript levels of MGMT and the effect of lomustine (r=-0.72; p<0.01), whereas the expression of MRP1 and cisplatin growth inhibition was positively correlated (r=0.82; p<0.005). This panel of xenografts should constitute a good tool for pharmacological and molecular studies in osteosarcoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Cytotoxic efficacy of bendamustine in human leukemia and breast cancer cell lines.

PURPOSE: The purpose of this study was to characterise bendamustine's cytotoxic and apoptotic activity in a panel of leukemia and breast cancer cell lines in comparison to its clastogenicity in murine bone marrow. METHODS: The cytotoxic effect of bendamustine was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT)-dye reduction assay. Induction of apoptosis was evidenced by DNA gel electrophoresis, nuclear staining, Western blot poly-(adenosine diphosphate-ribose) polymerase (PARP) cleavage, and flow cytometry. As a measure of hematological toxicity, the formation of chromosomal aberrations was investigated in bone marrow cells isolated from mice treated with low non-toxic doses of bendamustine and lomustine. RESULTS: Bendamustine was preferably active against leukemic cells of lymphoid origin and was found to induce apoptosis in SKW-3 and BV-173 cells as shown by oligonucleosomal DNA and nuclear fragmentation, PARP cleavage, and formation of a sub-G1 fraction. Myeloid and breast carcinoma cell lines were resistant towards bendamustine with the exception of HL-60 cells which exhibit an intermediate sensitivity. Bendamustine was found to have a very low clastogenic effect as compared with equimolar doses of lomustine. CONCLUSION: Taken together, the mode of action of bendamustine includes induction of apoptosis. The specific spectrum of activity and the unexpectedly low clastogenicity support the hypothesis that bendamustine in not a typical alkylating agent but exerts an additional mode of action, possibly as a purine antimetabolite.

Animals↗
PubMed2002

Recurrent malignant glioma in adults.

Meaningful palliation is possible for selected patients with recurrent malignant glioma (glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendroglioma, or anaplastic mixed oligoastrocytoma) using aggressive treatment. Although long-term disease-free survival occurs in fewer than 10% of patients, most who achieve such survival have been treated for multiple recurrences. Surgical resection with the placement of lomustine-releasing wafers is the only therapy proven in randomized trials to be beneficial for recurrent malignant gliomas. Reoperation is indicated when local mass effect limits the quality of life. Reoperation may make other treatments more effective by removing treatment-resistant hypoxic cells and thereby prolonging high-quality survival. Combination chemotherapy (including procarbazine and a nitrosourea) provides dramatic benefit for many recurrent anaplastic or aggressively behaving oligodendrogliomas and anaplastic mixed oligoastrocytomas. For other recurrent malignant gliomas, single-agent cytotoxic chemotherapy (eg, intravenous lomustine or platinums, oral carmustine, temozolomide, or procarbazine) appears to provide equivalent results and better quality of life at a lower cost than do the combinations of cytotoxic drugs. A randomized phase II trial demonstrates that temozolomide provides longer progression-free survival and better quality of life than standard-dose procarbazine in patients with recurrent glioblastoma multiforme. Because benefits of available cytotoxic chemotherapy for anaplastic astrocytoma and glioblastoma are small, participation in clinical trials is appropriate for most patients. Reirradiation (using stereotactic or three-dimensional conformal techniques with or without concomitant cytotoxic chemotherapy) as radiation sensitization can prolong high-quality survival in selected patients. Specific examples include radiosurgery with the gamma knife or with linear accelerators, intracavitary radiation with the newly US Food and Drug Administration-approved GliaSite (Proxima Therapeutics, Alpharetta, GA) radiation therapy system, low dose rate permanent-seed brachytherapy, and high dose rate stereotactic brachytherapy. Dexamethasone (used for the shortest time in the lowest effective doses) can provide symptomatic benefits. Osmotic diuretics such as mannitol reduce cytotoxic edema more rapidly.

Adult↗
PubMed1994

Hyperfractionated craniospinal radiation therapy for primitive neuroectodermal tumors: early results of a pilot study.

PURPOSE: To report the early results of hyperfractionated craniospinal radiation therapy with and without adjuvant chemotherapy for primitive neuroectodermal brain tumors (PNETs). METHODS AND MATERIALS: Thirty-nine patients with PNETs were classified as good-risk (23) or poor-risk (16), based on postoperative magnetic resonance imaging and a cytological examination of cerebrospinal fluid. All patients received hyperfractionated craniospinal radiation therapy; poor-risk patients subsequently received adjuvant chemotherapy with cisplatin, lomustine, and vincristine. The first six patients received 72 Gy to the primary tumor site and 24 Gy to the rest of the craniospinal axis. Subsequent patients received 30 Gy to the craniospinal axis. RESULTS: During a median of 1.9 years of follow-up (range 4 months to 3.5 years), there have been ten treatment failures in 39 patients, five in the good-risk group and five in the poor-risk group. Three failures occurred in the primary tumor site in areas that received 72 Gy; two were in poor-risk patients with residual disease after surgery; one was in a good-risk patient who had a gross total resection. Three failures occurred in the spine and craniospinal fluid of patients treated with 24 Gy. Four occurred in areas treated to 30 Gy; two of these were in areas thought to be undertreated because of treatment planning errors. Adjuvant chemotherapy was difficult to give to poor-risk patients because of poor bone marrow recovery, even with relatively low doses of lomustine (75 mg/m2). CONCLUSION: We think a dose of 24 Gy to the craniospinal axis is inappropriate because three of the six patients who received it had treatment failures outside the primary site. Whether 30 Gy is an appropriate dose for good-risk patients is still unclear. Even after a dose of 30 Gy, chemotherapy was difficult to give; this potentially limits the impact of adjuvant chemotherapy in poor-risk patients. Further follow-up is necessary to evaluate the use of hyperfractionated radiation therapy alone or with chemotherapy in patients with PNETs.

Adolescent↗
PubMed2003

Myeloid clonogenic assays for comparison of the in vitro toxicity of alkylating agents.

A battery of clonal assays for myeloid progenitor cells (HPP-CFC, CFU-gemm, CFU-gm, CFU-g) was utilized to evaluate the myelotoxicity of a series of alkylating agents representing the spectrum of clinical times to nadir. Bone marrow aspirates from normal volunteers were incubated with mechlorethamine, busulfan, melphalan, carmustine or lomustine for 1 h and then cultured in methylcellulose with 30% serum and cytokines. There was a concentration-dependent inhibition of colony formation and often a differential toxicity to the myeloid progenitors with the alkylators tested. On a molar basis, mechlorethamine and melphalan were the most toxic of the alkylator drugs to the myeloid precursors. The most sensitive progenitor was CFU-gemm with the lowest inhibitory concentration IC(70) concentrations for mechlorethamine, melphalan, carmustine and lomustine. Generally, there was great similarity for drug effects between CFU-g and CFU-gm with overlapping inhibition curves. HPP-CFC proved to be the least sensitive of the progenitors to the toxic actions of the drugs. While there was no correlation between the time to clinical neutropenic nadir and the most sensitive progenitor in the clonal assays, the CFU-gm assay remains a suitable method for determining the myelotoxic potential of cytotoxic agents.

Antineoplastic Agents, Alkylating↗
PubMed1996

Pre-radiation chemotherapy for malignant glioma in adults.

PURPOSE: To review our experience with pre-radiation chemotherapy for malignant glioma. METHODS: Consecutive adults with newly diagnosed glioblastoma, anaplastic astrocytoma, anaplastic oligodendroglioma and anaplastic mixed glioma with a Karnofsky Performance Score of 60 or greater were treated with one cycle of procarbazine, lomustine and vincristine or lomustine alone, prior to radiation. Computed tomographic scans were obtained soon after surgery, eight weeks later, after radiation, and at regular intervals thereafter. The effects of chemotherapy and subsequent radiation and durations of tumor control and survival were assessed in this single arm, single center, prospective trial. RESULTS: Thirty-seven patients started chemotherapy, 36 were rescanned eight weeks after diagnosis. Five patients (16%) responded to the first cycle of chemotherapy, three had glioblastoma and two anaplastic oligodendroglioma. Seven (19%) progressed during the first cycle, 6 had glioblastoma; with the addition of radiation one progressive case responded, three stabilized, and three continued to progress. Median times to progression and median durations of survival were 26 weeks and 60 weeks for the entire group, 24 weeks and 44 weeks for glioblastoma, and greater than 104 weeks for anaplastic astrocytoma. CONCLUSIONS: Most patients with glioblastoma do not respond to one cycle of nitrosourea-based chemotherapy given prior to radiation, but patients with anaplastic oligodendroglioma sometimes do. Patients with anaplastic astrocytoma may not respond to one cycle of chemotherapy, but often respond to subsequent radiation. Judging by survival results, radiation can be delayed eight weeks without appearing to compromise patient outcome. IMPLICATIONS: Pre-radiation chemotherapy with newer agents can be evaluated more fully in the future knowing that brief delays in radiation are unlikely to yield substantially inferior results.

Adult↗
PubMed2004

Second malignancies after chemotherapy and radiotherapy for Hodgkin disease.

The purpose of this preliminary study was to determine the incidence of second malignancies after combined-modality therapy for adults with Hodgkin disease and relate it to the details of initial treatment. We retrospectively studied 286 patients ranging in age from 16 to 88 years with stage I or II Hodgkin disease who were treated between 1980 and 1995 with chemotherapy followed 3 to 4 weeks later by radiotherapy. Patients received a median of three cycles of induction chemotherapy. Mitoxantrone, vincristine, vinblastine, and prednisone was used in 161 cases, mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) in 67 cases, Adriamycin, bleomycin, vinblastine, and dacarbazine in 19 cases, lomustine, vinblastine, procarbazine, and prednisone/doxorubicin, bleomycin, dacarbazine, and lomustine in 18 cases, and other chemotherapeutic regimens in the remaining 21 cases. The median radiotherapy dose was 40 Gy given in 20 daily 2-Gy fractions. Median follow-up of surviving patients was 7.4 years. There were 2,230 person-years of observation. Significantly increased relative risks (RR) were observed for acute myeloid leukemia (RR, 69.3; 95% CI, 14.3-202.6) and melanoma (RR, 7.3; 95% CI, 1.5-21.3). The 5-, 10-, and 15-year actuarial risks of acute myeloid leukemia were 0.8%, 1.3%, and 1.3%, respectively. Patients treated with MOPP had the highest 15-year actuarial risk of leukemia (1.6%). The 5-, 10-, and 15-year actuarial risks of solid tumors were 1.9%, 9.3%, and 16.8%, respectively. Consolidative radiotherapy to both sides of the diaphragm resulted in a trend toward an increased risk of solid tumors relative to radiotherapy to only one side of the diaphragm (p = 0.08). In an effort to reduce the risk of second malignancies, we have stopped using the alkylating agents nitrogen mustard and procarbazine and elective paraaortic and splenic radiotherapy after chemotherapy.

Adolescent↗
PubMed2004

Chemotherapy-induced cell death in primary cerebellar granule neurons but not in astrocytes: in vitro paradigm of differential neurotoxicity.

The nervous system is frequently the site of symptomatic toxicity of antineoplastic agents. However, there is limited information about the differential vulnerability of neurons, astrocytes and glioma cells. We have analyzed the effects of four chemotherapeutic drugs (lomustine, cisplatin, topotecan and vincristine) on primary cerebellar granule neurons and astrocytes derived from rats. All drugs led to cell death in cerebellar granule neurons in a concentration-dependent manner. Comparison of the EC50 values for cerebellar neurons and astrocytes with the median EC50 values of 12 malignant glioma cell lines demonstrated a large therapeutic range for lomustin and cisplatin. Further, this comparison revealed a 100-fold higher sensitivity of cerebellar neurons towards vincristine and 10-fold higher sensitivity towards topotecan compared with glioma cells. Astrocytes were generally resistant to vincristine. In cerebellar granule neurons, vincristine and to a lesser extent topotecan induced caspase 3 and caspase 9 cleavage, and enhanced caspase activity and Akt-dependent expression of phosphorylated BAD. zVAD-fmk, a caspase inhibitor and brain-derived neurotrophic factor (BDNF), but not MK-801, a non-competitive NMDA receptor antagonist, significantly reduced vincristine- or topotecan-induced cell death.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Recognition and management of gliomas.

Gliomas are the most frequent primary brain tumours. They include astrocytic gliomas, oligodendrocytic gliomas, ependymomas and gliomas with mixed cell populations. Each glioma type consists of both low-grade and malignant atypical varieties. The low-grade tumours occur predominantly in children and young adults, and the malignant forms in older people. The presenting symptoms are epileptic seizures, headache and mental confusion. Focal neurological symptoms and findings, such as hemiparesis, are mostly associated with the malignant forms. Magnetic resonance imaging (MRI) scan of the brain with and without gadolinium contrast demonstrates the tumour. However, stereotactic biopsy or surgical resection is necessary to obtain the correct pathological diagnosis, except for diffuse pontine astrocytomas, which have an unmistakeable imaging appearance and for which biopsy has substantial risks. Treatment depends on the pathological diagnosis. Complete surgical resection may be curative for low-grade tumours. Postoperative radiotherapy is recommended for partially resected tumours. Most malignant gliomas require aggressive combination therapy with radiotherapy and chemotherapy after maximal surgery. The standard initial regimens are nitrosourea-based chemotherapies, such as carmustine alone, a combination of procarbazine, lomustine and vincristine, or a combination of thioguanine, procarbazine, lomustine and hydroxycarbamide (hydroxyurea). Unfortunately, the prognosis of malignant gliomas is generally poor despite aggressive treatment, because of their infiltrative nature and high relapse rate.

Brain Neoplasms↗
PubMed1999

Oral combination chemotherapy in the management of AIDS-related lymphoproliferative malignancies.

An oral combination chemotherapy regimen initially developed for AIDS-related non-Hodgkin's lymphoma includes lomustine (CCNU), etoposide, cyclophosphamide, and procarbazine. This regimen takes advantage of oral administration, the in vitro synergy of these drugs and their first-line efficacy in lymphoma, and the ability of lomustine and procarbazine to cross the blood-brain barrier. This regimen was used to treat 38 patients with AIDS-related non-Hodgkin's lymphoma. The overall objective response rate was 66% (34% complete response rate) with a 5% CNS relapse rate, and a median survival duration of 7.0 months. One-third of the patients survived for 1 year, 11% for 2 years, and half of the patients survived free from progression of their lymphoma. On the basis of these results, this oral regimen was modified and administered to 5 patients with AIDS-related primary CNS lymphoma as part of a sequential combined-modality chemotherapy and radiation regimen. Rapid progression of CNS disease was observed in this group of patients, with a median survival duration of 1.0 month. The identical regimen was administered to 7 patients with AIDS-related Hodgkin's disease: we observed a 71% partial remission rate and a median survival duration of 7.0 months. Myelosuppression remains the most significant clinical toxicity. Our results with this oral regimen appear comparable to those of standard intravenous combination chemotherapy regimens in patients with AIDS-related non-Hodgkin's lymphoma.

Administration, Oral↗
PubMedDate not supplied

Effects of combined selenium and vitamin E administration on DNA in Walker tumor bearing Wistar rat exposed to cytostatic acute treatment.

Previous studies have showed that organic Se and Vitamin E have a significant protective effect when administered in combination with cytostatics. This paper reports the investigation on effects of mixed administration Orgasel 50 and Vitamin E in Wistar rat with experimentally induced Walker tumor under acute cytostatic treatment, with emphasis on two aspects: a) the influence of antioxidants upon liver unscheduled DNA biosynthesis under cytostatic (Lomustin) acute aggression; and b) the potential improvement of cytostatic effects by antioxidants treatment in tumor. Two lots of animals were used: lot 1 - Orgasel 50 and Vitamin E administered 7 days before the initiation of tumor induction and lot 2 - the antioxidants were concomitantly administered with tumor cell inoculation. The Walker tumor (an epithelial carcinoma) cells were subcutaneously injected (5 x 10(6) cells/0.5 ml in isotonic saline solution); the first tumor nodules appeared in 4 days; the tumor has reached the appropriate dimensions in 12 days. The unscheduled DNA biosynthesis caused by Lomustin in rat liver as well as the replicative DNA biosynthesis taking place in Walker tumor cells were assessed radioisotopically by measuring the uptake of 3H-Thymidine (200 microCi / 100 g.b.w.). Our observations regarding the role of antioxidant treatment suggest: 1) a benefic effect on DNA alkylant-induced lesions, expressed by a decrease in the level of 3H-Thymidine uptake in liver and, 2) an increase of the inhibitory activity of cytostatic on DNA replication biosynthesis in tumor cells, suggested by lower 3H-Thymidine incorporation in tumor cells. The most significant results were showed in both analyzed tissues, when the Orgasel 50 + Vitamin E administration begins at the same time with the tumor cell inoculation. These findings clearly show the organic Se salts and Vitamin E constitute a valuable adjuvant in anticancer medication, increasing the interest for the application of these antioxidants in cancer therapy and prevention.

Administration, Oral↗
PubMed1986

Northern California Oncology Group protocol 6G91: response to treatment with radiation therapy and seven-drug chemotherapy in patients with glioblastoma multiforme.

The Northern California Oncology Group (NCOG) conducted a nonrandomized phase II study to evaluate the benefit of a seven-drug chemotherapy protocol (NCOG 6G91) in patients with glioblastoma multiforme (GM). Time to tumor progression was the primary end point of the study. The treatment consisted of 5-FU and lomustine administered after surgery and before radiation therapy, hydroxyurea and misonidazole during radiation therapy, and procarbazine and vincristine alternated with carmustine and 5-FU after radiation therapy. Ninety patients entered the study; data from the 64 patients with GM who completed radiation therapy and at least started the postradiation chemotherapy regimen and returned for follow-up examination are analyzed in this report. The median time to tumor progression in the 64 adequately treated patients was 42 weeks; the 25th percentile value was 60 weeks. A Cox multivariate analysis showed that age and extent of surgical resection were important prognostic variables in patients with GM. The results of this treatment regimen were similar to those of a previous NCOG protocol (6G61), which consisted of hydroxyurea during radiation therapy followed by chemotherapy with carmustine or a combination of lomustine, procarbazine, and vincristine.

Adult↗
PubMed1993

Chemotherapy for malignant gliomas.

An increase in the incidence of malignant gliomas has been noted over the last two decades. Chemotherapy, either adjuvant or at recurrence, has extended the survival of patients with malignant gliomas. Oligodendrogliomas and anaplastic astrocytomas represent the most chemosensitive tumors, while glioblastomas have been relatively resistant to any treatment modality. The most active agents include carmustine, procarbazine, and eflornithine, and combinations such as lomustine, procarbazine and vincristine, or thioguanine, dibromodulcitol, procarbazine, lomustine, fluorouracil and hydroxyurea. Although chemotherapy has demonstrated some efficacy against malignant glioma, new therapeutic strategies are needed for this devastating disease.

Antineoplastic Agents↗
PubMed1993

Degradation and inactivation of antitumor drugs.

Chemical methods for the degradation of 11 antineoplastic drugs [etoposide, teniposide, bleomycin, mitomycin C, cisplatin, cis-dichloro-trans-dihydroxy-bis(isopropylamine) platinum IV (CHIP), cyclophosphamide, ifosfamide, carmustine, lomustine, and methotrexate] were investigated. The success of the degradation procedures was assessed by HPLC and degree of biological inactivation by mutagenicity assays. The most widely applicable procedure was oxidation with potassium permanganate or 5.25% sodium hypochlorite solution (bleach). Oxidation completely degraded and inactivated etoposide, teniposide, bleomycin, mitomycin C, and methotrexate. In addition, oxidation followed by nucleophilic substitution resulted in the complete degradation and inactivation of cyclophosphamide and ifosfamide. Although carmustine and lomustine were chemically degraded by treatment with acidic potassium permanganate, the resulting reaction mixtures remained mutagenic. Therefore, this procedure cannot be recommended. The platinum-containing compounds, cisplatin and CHIP, were rendered nonmutagenic by reaction with sodium diethyldithiocarbamate. These easily performed, relatively safe procedures can be used to prevent exposure to mutagenic wastes and spills in the hospital setting.

Antineoplastic Agents↗
PubMed1976

Single-agent chemotherapy of brain tumors. A five-year review.

Identification of effective single chemotherapeutic agents for brain tumors must precede the rational use of multiple drug combinations. In phase 2 trials beginning in 1968, 158 patients with intrinsic brain tumors (mostly recurrent malignant astrocytomas) were considered evaluable. The larger trials with more effective drugs produced these results: carmustine (BCNU) response rate, 47%, with median duration of nine months; lomustine (CCNU), 44%, with median duration of six months; procarbazine hydrochloride, 52%, with median duration six months; carmustine and vincristine sulfate combined, 44%, with median duration of only four months; and BIC (5-[3,3-bis(2-chloroethyl)-1-triazeno]imidazole-4-carboxamide), 38%, with median duration of five months. Administration of glucocorticoids was not found to bias the frequency of response. Forty-seven patients, 26 of whom had responded to the initial drug, received a second drug. Among 26 patients who were evaluable, only four responded to the second drug.

Astrocytoma↗