Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Second-look operations for glioblastomas, one of the most malignant types of brain tumor, were performed after the administration of chemotherapeutic treatments of general-VM 26 plus ACNU, local-MTX, or interferon-beta in each of ten, two, and three cases, respectively. Patients who had received the treatments were divided into two groups, living and deceased, as of August 1982. Therapeutic evaluation was performed with clinical parameters. Among the cases of CR, one (a 14-year-old female) had undergone surgery four times in the four years following onset, and no trace of tumor shadow appeared on the CT grams that were taken one month after the last surgery. Her performance was evaluated as almost 100% (ECOG). In cases of local administration, one case, which had been treated with IFN-beta, demonstrated an apparent decrease in the growth fraction and a pronounced decrease in tumor progression potency. Cell kinetic analyses were also performed, and cell cycle time and growth fraction were estimated by computer with the aid of flow cytometry. Efficacious chemotherapy yielded a decreased value of the growth fraction and an increase in cell cycle time. The decreased value of the growth fraction demonstrates especially well the effectiveness of a chemotherapeutic regimen. The cell kinetic analyses aided in the rational establishment of a chemotherapeutic regimen. Second-look operations for malignant brain tumors will enable more effective refinements in chemotherapeutic regimens and more successful results.
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PMID:[Second-look operations and chemotherapy for malignant tumors of the brain]. 657 17

The authors report five patients with primary intracerebral non-Hodgkin's lymphoma who were treated with several cycles of intra-arterial injection of 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) at doses of 80 to 100 mg/m2/injection at several monthly intervals. There was no simultaneous use of steroids, and no patients had concomitant immunosuppression; no patient was human immunodeficiency virus positive. This therapy was initially used in four patients with advanced recurrent lymphoma. These patients experienced tumor progression despite our institutional standard therapy comprising cranial irradiation followed by repeated courses of systemic multi-agent chemotherapy (cyclophosphamide, vincristine, adriamycin, and prednisolone) more than 3 months previously. Based upon brain computed tomography scans and clinical neurologic examinations, three of the four cases showed partial responses ranging from 10 to 12 months in duration, whereas the other patient remained stable without worsening for 8 months. A fifth case was particularly noteworthy; this patient had no prior therapy and intra-arterial chemotherapy alone induced an 18-month, disease-free remission. No significant therapy-related complications nor neurotoxicity were seen. These results suggest that intra-arterial administration of ACNU may be a potential candidate for intracerebral lymphoma therapy.
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PMID:Chemotherapeutic effects of intra-arterial administration of ACNU in primary intracerebral non-Hodgkin's lymphoma. 821 54

To assess whether therapeutic efficacy is related to intra-arterial (IA) mannitol infusion prior to ACNU and cisplatin (CDDP) for brain metastases from lung cancer, clinical results of patients with and without IA mannitol infusion were compared. Thirty-nine patients were randomly assigned to either a mannitol infusion group (group A) or a non-mannitol infusion group (group B). There were 22 patients in group A and 17 in group B. During radiotherapy, ACNU and CDDP, at a dose of 100 mg/body, were given through the common carotid artery at a rate of 20 mg/min. In group A, 50 ml of 20% mannitol was injected intra-arterially at a rate of 50 ml/min immediately prior to the injection of chemotherapeutic agents. Major complications, such as seizure and neurotoxicity, were not observed. Complete response (disappearance of enhanced tumor mass) was obtained in 72% of group A and in 67% of group B. The median time to tumor progression was 40 weeks for group A and 22 weeks for group B. The median survival time (MST) was 45 weeks for group A and 30 weeks for group B. The survival time was significantly longer in group A as compared to group B (p < 0.05). When the patients who died of failure of vital organ systems other than brain complications were excluded in calculating the survival time, the MST was 69 weeks for 11 patients of group A and 34 weeks for 7 patients of group B. These data suggest that an effort to increase drug delivery to the brain tumor may indeed lengthen the survival time of patients with brain metastases from lung cancer.
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PMID:[Intra-arterial ACNU, CDDP chemotherapy for brain metastases from lung cancer: comparison of cases with and without intra-arterial mannitol infusion]. 833 9

Over the past 25 years, we have treated 17 patients with chiasmo-hypothalamic astrocytomas. Before 1988, the initial treatments consisted of surgery and/or radiotherapy, while since 1989, 4 children (1 male, 3 females, aged 3-8 years) were treated primarily with chemotherapy. None of them was associated with neurofibromatosis. After a biopsy of the tumor, the intravenous administration of ranimustine (MCNU; 30-86 mg/m2) and/or nimustine (ACNU; 30.3-64.1 mg/m2) was given without radiation therapy. Chemotherapy was usually given as an out-patient, with a total of 5-13 courses. The total doses of MCNU and ACNU administered ranged from 150 to 570 mg and from 64.8 mg to 100 mg, respectively. After chemotherapy 2 patients showed clinical improvement and tumor regression on neuro-imaging, while one patient showed clinical improvement and tumor size stabilization on neuro-imaging. The remaining one child, however, showed a clinical worsening and tumor progression on neuro-imaging studies. He was thus treated with a second chemotherapy regimen with carboplatin and etoposide, which brought about tumor regression. The acute and subacute toxicity of chemotherapy was mild. All patients are now leading almost normal lives with a median of 43 months after diagnosis. Although a longer and more careful clinical observation is required, the authors conclude that chemotherapy with MCNU and/or ACNU may benefit patients with unresectable pilocytic astrocytoma requiring treatment. The advantages of this therapy include its mild side effects and the lack of any hospitalization in most patients. It may also delay the need for radiation therapy, which can have a deleterious effect on the young developing brain.
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PMID:Chemotherapy for progressive pilocytic astrocytomas in the chiasmo-hypothalamic regions. 859 96

We studied the sensitivity of human melanoma (Bro strain) xenografts to drugs of the nitrosoalkylurea (NAU) class: nitrosomethylurea (NMM), karmustin (BCNU), nimustin (ACNU), nitrulin, and ADEKO. High antitumor activity of NAM was shown when the drugs were applied not only at the early, but also at the late stages of tumor progression (tumor mass 400 and 1200 mg, respectively). The therapeutic effect of the drugs was estimated with the use of criteria characterizing the kinetics of tumor regression, increased life span, and survival of treated animals. After early administration of the drugs (Day 4 after tumor transplantation), 67% and 50% of animals survive under the influence of nitrulin and ACNU, respectively, while the rate of tumor regression increased in the sequence nitrulin < karmustin < NMM < ACNU. After late administration (11 days after tumor transplantation), NMM was most effective at increasing survival (35% of survived animals by 35 days of observation), while the rate of tumor regression increased in the sequence ADEKO < NMM < karmustin < nitrulin < ACNU.
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PMID:[Sensitivity of human melanoma xenografts to nitrosoalkylurea antineoplastic agents]. 975 Apr 35

Twenty-eight patients who were previously treated by aggressive surgery and radiation and were diagnosed with supratentorial malignant gliomas received a combination of nimustine hydrochloride; 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), cisplatin and etoposide (ACE therapy) as primary treatment. Cisplatin and etoposide were given at doses of 20 and 60 mg/m2/day for 5 days, respectively, ACNU doses 80 mg/m2/day on the first day. Treatment was repeated at 4-week intervals for up to 3 cycles. Seventeen patients (60.7%) complained of nausea. Grade 3 or 4 hematological toxicity occurred in 11 patients (39.3%), and grade 3 or 4 renal toxicity occurred in 2 patients. The percentage of patients who showed complete or partial response was 28.6% (8/28). The median time of tumor progression was 40 weeks, and the median survival time was 146 weeks. There were some long-surviving patients who may have benefited from ACE combination. This study demonstrated the effects of ACE combination in patients with supratentorial malignant gliomas.
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PMID:A phase II study of nimustine hydrochloride, cisplatin, and etoposide combination chemotherapy for supratentorial malignant gliomas. 1121

We investigated stereotactic intratumoral microinfusion of nimustine (ACNU) in recurrent brain tumors. Eligibility required histologic confirmation of glioma recurrence despite standard radiotherapy and chemotherapy as well as enhancement of the recurrence with gadolinium on magnetic resonance imaging (MRI). A total intratumoral dose of 10 mg of ACNU was administered continuously with a microinfusion pump over an average of 13h. Fifteen infusions were given in nine patients. All patients completed the treatment safely. On MRI, necrotic changes surrounded the infusion area in all patients, and tumor progression was inhibited or performance score was improved in seven of nine patients. No symptomatic systemic toxicity was evident, although one patient developed permanent left oculomotor palsy locally after treatment of a left medial temporal tumor. It is concluded that direct microinfusion of ACNU into recurrent gliomas can induce tumor necrosis and inhibit tumor growth.
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PMID:Intratumoral microinfusion of nimustine (ACNU) for recurrent glioma. 1151 70

Thirty glioblastoma patients treated at our institute between April 1998 and September 1999 were randomized in a two-arm study to receive carboplatin plus ACNU intraarterial (IA) chemotherapy (arm A) or cisplatin plus BCNU intravenous (IV) treatment (arm B). After the second course of chemotherapy and before the third cycle they also received concomitant radiotherapy, consisting of a median dose of 56.5 Gy. There were 3 (21.4%) partial responses and 11 (78.6%) disease stabilizations in group A. There were 5 (33%) partial responses and 10 disease stabilizations in group B. Time to tumor progression was 5.2 and 5.8 months for IA and IV treatment respectively. Median survival time was 18.3 months for arm A patients and 18.6 for arm B patients. Our IA chemotherapy schedule has produced no conclusive evidence of benefit compared with intravenous treatment. Moreover, its cost-benefit ratio is not good enough to justify its continued pursuit.
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PMID:Intra-arterial ACNU and carboplatin versus intravenous chemotherapy with cisplatin and BCNU in newly diagnosed patients with glioblastoma. 1252 77

Hypoxic cells play a key role in the radioresistance of malignant glioma. Interferon-beta, ACNU as nimustine hydrochloride and radiotherapy (IAR) is a common therapy for malignant glioma in Japan. Since hyperbaric oxygenation (HBO) increases oxygen pressure in glioma tissue, we applied a modified IAR therapy, radiotherapy after HBO combined with interferon-beta and ACNU (HBO/IAR therapy), for supratentorial malignant gliomas. Daily radiation therapy was completed within 15 min after HBO. We assessed HBO/IAR with respect to toxicity, response rates and the time of tumor progression (TTP). We also examined the incidence of responses by some prognostic factors before HBO/IAR, namely, age, Karnofsky performance scale (KPS), histological type, tumor size, tumor site and operation type. Of 39 patients who participated in this study, 35 underwent a complete schedule of HBO/IAR therapy in which toxicity was permissible. Thirty patients (76.9%) either maintained or increased KPS during HBO/IAR with a mean duration of 68 +/- 14 days. The response rates (CR + PR%) for glioblastoma, anaplastic astrocytoma and overall were 50%, 30% and 43%, respectively. The incidence of therapeutic responses among all prognostic factors before HBO/IAR did not significantly differ. Median TTP for patients with glioblastoma, patients with anaplastic astrocytoma, and overall were 38, 56 and 43 weeks, respectively. The present study suggested that HBO/IAR therapy could be applied to especially patients with poor prognostic factors, because of its short treatment period, its permissible toxicity and identical response to patients with good prognostic factors.
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PMID:A phase II study of radiotherapy after hyperbaric oxygenation combined with interferon-beta and nimustine hydrochloride to treat supratentorial malignant gliomas. 1262 55

Non-invasive loco-regional electro-hyperthermia (EHT) plus alkylating chemotherapy is occasionally used as salvage treatment in the relapse of patients with high-grade gliomas. Experimental data and retrospective studies suggest potential effects. However, no prospective clinical results are available. We performed a single-center prospective non-controlled single-arm Phase I trial. Main inclusion criteria were recurrent high-grade glioma WHO Grade III or IV, age 18-70, and Karnofsky performance score > or = 70. Primary endpoints were dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) with the combined regimen. Groups of 3 or 4 patients were treated 2-5 times a week in a dose-escalation scheme with EHT. Alkylating chemotherapy (ACNU, nimustin) was administered at a dose of 90 mg/m(2) on day 1 of 42 days for up to six cycles or until tumor progression (PD) or DLT occurred. Fifteen patients with high-grade gliomas were included. Relevant toxicities were local pain and increased focal neurological signs or intracranial pressure. No DLT occurred. In some patients, the administration of mannitol during EHT or long-term use of corticosteroids was necessary to resolve symptoms. Although some patients showed responses in their primarily treated sites, the pattern of response was not well defined. EHT plus alkylating chemotherapy is tolerable in patients with relapse of high-grade gliomas. Episodes of intracranial pressure were, at least, possibly attributed to EHT but did not cause DLTs. A Phase II trial targeting treatment effects is warranted on the basis of the results raised in this trial.
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PMID:Transcranial electro-hyperthermia combined with alkylating chemotherapy in patients with relapsed high-grade gliomas: phase I clinical results. 2003 71


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