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PubMedDate not supplied

Differential sensitivity to mitomycin C between human RSa cell line and its derivative UVr-1.

To study cellular signaling factors responsible for the susceptibility of human cells to cell proliferation inhibition by anticancer drugs, human RSa cell line and its ultraviolet-resistant derivative UVr-1 were compared with respect to their sensitivity to the anti-proliferative effects of mitomycin C (MMC), 5-fluorouracil, nimustine (ACNU), cisplatin, pirarubicin (THP), bleomycin, methotrexate and ifosfamide. RSa cells were found to be highly sensitive to MMC by MTT assay compared to UVr-1 cells. The half maximum inhibition concentration of MMC against proliferation of RSa cells was approximately 100 ng/ml while that of UVr-1 cells was greater than 1 microgram/ml. There was no significant difference observed between RSa and UVr-1 cells in the sensitivity to other seven drugs examined. Analysis by flow cytometry revealed that the cell cycle of RSa was completely blocked at the G2/M phase 40 h after treatment with MMC at a concentration of 100 ng/ml whereas a substantial proportion of UVr-1 cells was not arrested at that phase even in the presence of MMC. Further immunoblot analysis on MMC-induced signal transduction showed that the amounts of phosphorylated ERK MAP kinases were increased in UVr-1 cells to a greater extent than those in RSa cells after treatment with MMC for longer than 2 h. However, the increase in p21Cip1 was observed in RSa cells 1 h after addition of MMC but was not observed in UVr-1 cells. These distinct signaling pathways might account for the differences in sensitivity to MMC between RSa and UVr-1 cells.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

Efficacy of single-bolus vs. frequent low-dose treatment with nitrosourea in experimental gliomas.

BACKGROUND: Malignant glioma remains a fatal disease. Continuous or frequent low-dose (FLD) chemotherapy with nitrosoureas reportedly causes fewer side-effects than single-bolus therapy without decreasing the antitumour effects. MATERIALS AND METHODS: To study the effect of FLD treatment with nimustine (ACNU) in rats with glioma, we intracerebrally inoculated with C6 glioma cells. We began the ACNU treatment 5 or 8 days later (total dose, 25 or 40 mg/kg) i.p. as either one bolus or smaller doses spread over 5 days week. RESULTS: At a total dose of 25 mg/kg beginning at day 8, survival duration did not differ between untreated controls and the FLD group, while the bolus significantly prolonged survival; the FLD group showed some improvement beyond control survival at 40 mg/kg (each p <0.001). Beginning treatment after 5 rather than 8 days prolonged survival somewhat further. CONCLUSION: FLD treatment with ACNU is less effective against experimental glioma in rats than bolus treatment.

Animals↗
PubMed1992

[Experimental study on the effect of injection with anticancer agent-oil suspension].

Local injection of an anticancer agent guided by endoscopy is thought to be effective for cancerous lesion associated with lymph node metastasis, if the anticancer drugs are drained into the lymph nodes. In the experimental study, anticancer drug-oil (nimustine-Lipiodol) (N-L) suspension (5 mg/ml) was injected into the tumor (Lewis lung cancer) that had been implanted sub dorsally in mice (57 black/6 mice) for the purpose of finding out the antitumor effect on the primary lesion. Then it was injected into sarcoma-180 that had been implanted into hind feet of mice (ICR mice) for the purpose of finding out the antitumor effect on metastatic lymph nodes. The results showed that the N-L suspension was effective for the primary cancerous lesion and metastatic lesions.

Animals↗
PubMed2003

[Role of thallium SPECT for evaluating the effect of maintenance chemotherapy against malignant gliomas].

Thallium (Tl)-201 single-photon emission computed tomography (SPECT) is a useful tool for detecting brain tumors. In this study, we evaluated the utility of Tl-201 SPECT for determining the effect of maintenance chemotherapy with ACNU (nimustine hydrochloride)/VCR (vincristine sulfate) against malignant gliomas. The cases were comprised of 16 glioma cases; 6 astrocytomas, 2 anaplastic astrocytomas, and 8 glioblastomas. We first analyzed the correlation between Tl-201 uptake ratio and proliferative activity of the tumor, using Ki-67 immunohistochemistry in 13 cases of glioma. The uptake ratio of Tl-201 correlated with the Ki-67 staining indices (SI), and a closer correlation was obtained using Tl-201 delayed images than with the early images. We also analyzed the chronological changes of Tl-201 uptake ratio and volume of abnormal area evaluated by MRI T2-weighted imaging (MRI T2WI), in 10 cases of malignant glioma during maintenance chemotherapy. The Tl-201 uptake ratio gradually decreased with the effect of maintenance chemotherapy, and the sensitivity was superior to MRI findings. Together with MRI, Tl-201 SPECT is considered to be a useful indicator for evaluating the effect of maintenance chemotherapy against malignant gliomas.

Adult↗
PubMed1991

[Intrathecal distribution of ACNU by various modes of its administration analyzed by HPLC and autoradiography].

Various modes of administration of ACNU (nimustine hydrochloride) were tried to make clear which mode is the best method to obtain intrathecal diffuse distribution of ACNU to match the condition of killing of glioma cells (10 micrograms/ml; greater than 30 min.). Tried modes of administration included 1)bolus injection into ventricular cavity, 2)bolus injection into cisterna magna, 3)bolus injection into lumbar subarachnoid space, 4)ventriculo-lumbar perfusion, 5)chiasmatic cistern-lumbar perfusion. Used dose of ACNU was 5 mg/body for all modes of administration. ACNU level in CSF was measured by HPLC method specially developed by authors. To make clear intrathecal distribution of ACNU, autoradiography using 14C-ethylene-ACNU was studied after administration of 10 muCi/Kg of radioactive ACNU. The images were studied by image analyzer system (BAS-2,000 system developed by Fuji Film Co. Ltd). Among the modes of administration tried, ventriculo-lumbar perfusion method gave the best results in terms of lumbar, ventricular, cisterna magna, and basal cistern distribution of ACNU to match the cell kill condition experimentally ascertained. Although, bolus injection of ACNU into cisterna magna gave sufficient amount of ACNU in lumbar region, the initial level of ACNU was too high in cisterna magna, and administration of ACNU once a week for three times in a canine cisterna magna resulted in considerable deterioration of brain stem and basal structure. In addition to it, the level of ACNU in ventricular cavity was not detectable. Lumbar bolus injection resulted in also too much ACNU accumulation at the injected lumbar area, and at the cisterna magna region, ACNU was not detectable.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

[Antitumor spectra of ranimustine against various human tumors].

Ranimustine (MCNU) has been shown to exhibit high antitumor activity and broad antitumor spectra against various experimental tumors. These effects were comparable to those of nimustine (ACNU). However, clinical applications of ACNU are indicated to various types of malignancies including solid tumors, while those of MCNU are almost limited to hematological ones. Therefore, the antitumor activity of MCNU was examined against 55 specimens from 15 types of solid tumors and compared with those of ACNU and 8 other drugs. Drug sensitivity was examined by a morphological method measuring the proportion of degenerative changes in the nucleus of drug-treated and untreated tumor cells. MCNU showed antitumor activities (measured by karyorrhexis) against adenocarcinoma of the lung, squamous cell carcinoma of the lung, renal cell carcinoma, bladder tumor, ovarian cancer and brain tumor. In addition, MCNU and ACNU showed a similar positive rate (15-16%) in this experiment and this was the highest among all drugs examined. Although MCNU and ACNU showed similar antitumor spectra, a clear difference was observed when the antitumor activities of both drugs were compared in each identical specimen. These results clearly suggest that MCNU is worthy of clinical study to examine the antitumor activity against various solid tumors.

Antineoplastic Agents↗
PubMed1990

[Augmentation of TNF- and lymphotoxin-mediated cytotoxic effect in the combined use of ACNU and involvement of oxygen free radicals].

Roles of oxygen free radicals in recombinant human TNF- and human lymphotoxin (LT)-mediated cytotoxicity have been examined. Nimustine (ACNU), which inhibits glutathione reductase, and buthionine sulphoximine (BSO), an inhibitor of glutathione (GSH) synthesis, were used to modify the steady-state level of intracellular H2O2. TNF-mediated cytotoxicity was augmented when ACNU was added simultaneously to target L cells or Meth A tumor cells. Similar augmented effect was observed when TNF or LT was added to ACNU-treated target cells. However, the addition of GSH nullified the augmentation of TNF-mediated cytotoxicity to ACNU-treated Meth A tumor cells. Meth A tumor cells were pretreated with BSO for 24 hr, and thereafter TNF or LT was added in the presence or the absence of BSO. The cytotoxic effect of TNF and LT was augmented by the treatment of the cell with BSO or simultaneous addition of BSO. High degree of the augmentation was obtained when the pretreatment with BSO and further addition of BSO were combined. These results suggest that oxygen free radicals are closely involved in TNF- and LT-mediated cytotoxicity and the modulation of intracellular GSH level alters the degree of the cytotoxicity of these cytotoxins.

Animals↗
PubMed1989

[Radiochemotherapy-related changes in the brain parenchyma of glioma patients evaluated repeatedly by C15O2, C15O, 15O2, and 18F-fluorodeoxyglucose (FDG) PET].

The aim of this study was to evaluate effects of radiochemotherapy on blood flow and metabolism using C15O2, C15O, 15O2, and 18F-fluorodeoxyglucose positron emission tomography (PET). Conventional, external radiotherapy (180-200 cGy/5 fractions/week) using 60Co or a 10 MV linear accelerator was given in conjunction with chemotherapy of nimustine hydrochloride (ACNU) and tegafur (FT-207) in eight patients with gliomas. Regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen extraction fraction (rOEF), oxygen consumption (rCMRO2), and glucose consumption (rCMRG1) were longitudinally examined before the treatment, and at an early stage (within one month) and a late stage (three to thirty-one months with a mean of 12 months) after radiochemotherapy. Contralateral gray and white matter to the tumor was selected as regions of interest (ROIs), because these portions were irradiated with larger doses compared to other brain parenchymal regions through parallel opposing fields. Maximum doses to the ROIs varied between 20 and 61 Gy. Calculated as a function of time-dose-fractionation, nominal standard doses (NSD) ranged from 566 to 1729 ret, and 344 to 1062 neuret; equivalent doses (ED) equaled 432 to 1327 rads. At the early stage, rCBF and rCBV increased in the contralateral gray and white matter; gray matter rOEF decreased significantly (p less than 0.05 by a paired-t test) from that of the pretreatment study, probably due to decompression of the tumor bulk and radiochemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

[Small cell lung cancer: a retrospective analysis of results of chemotherapy and combined modality treatment].

In order to assess the development of treatments and the curability of SCLC, we analyzed a total of 181 patients entered in our protocol studies since 1976. Between 1976 and 1981, 37 patients (20 LD and 17 ED) were treated with COMP, a 4-drug combination of cyclophosphamide (CTX), vincristine (VCR), methotrexate, and procarbazine. During the period, chest irradiation (RT) was administered optionally to those with LD. Between 1981 and 1986, 112 patients (56 each of LD and ED) were treated with a cyclic alternating chemotherapy of the COMP and VAN, a 3-drug combination of etoposide (VP-16), adriamycin (ADM), and nimustine. In this study, we randomized LD patients either to receive CT alone or CT plus chest RT of 40 Gy to assess the role of chest RT in the treatment of patients in LD. Complete responders were also randomized either to receive prophylactic cranial irradiation (PCI) or not. Thereafter, a pilot phase II study of a hybrid regimen has been conducted in 32 patients (16 each of LD and ED), in which CTX, ADM and VCR (CAV) was given on day 1, and cisplatine and VP-16 (PVP) on days 8 and 9. Chest RT was administered mandatory to LD in this study. The median survival time (MST) has been prolonged with an improvement in response rate over CT in both LD and ED: MST of LD was 10 months for COMP, 14 months for COMP-VAN, and not achieved for CAV-PVP hybrid regimen (13 of 16 patients alive between 10 and months), while that of ED was 8 months for COMP, 11 months for COMP-VAN, and 13 months for CAV-PVP hybrid regimen. The randomized study comparing CT alone and CT plus chest RT revealed that chest RT played a substantial, but not significant, for long survival in LD. Finally 13 of 149 patients treated between 1976 and 1986 were long-term, disease-free survivors beyond 2 years (12 LD and 1 ED). Two of them who had not received PCI had a relapse in the brain, but the remaining 11 patients are alive and disease-free between 28 and 84 months. These results imply that SCLC is potentially curable, but it will be difficult to achieve a cure in a substantial proportion of patients with the disease.

Adult↗
PubMed1989

Most effective route of administration and utilization of high-dose chemotherapy with bone marrow transplantation in rats.

In order to find out which anticancer drugs could utilize to the best advantage a syngeneic bone marrow transplantation in high-dose chemotherapy for cancer, we tested six drugs [nimustine hydrochloride (ACNU), Adriamycin, cyclophosphamide (CY), mitomycin c, vindesin, etoposide] in Sprague-Dawley rats from a standpoint of the beneficial effect of bone marrow transplantation (BMT). Two or three varying doses of each drug were administered i.v. on Day 0, followed by the injection of syngeneic bone marrow (BM) cells (5 x 10(7), i.v.) on Day 2, and the animals were observed for over 60 days. Adriamycin caused high rates of peripheral neuropathy, and was therefore judged to be inappropriate for high-dose chemotherapy-BMT in this animal model. Among the other five drugs, a beneficial effect of BMT was observed only with CY (300-400 mg/kg) and ACNU (40 mg/kg). In order to enhance the beneficial effect of BMT observed with CY and ACNU, a way of drug administration was designed and carried out. Consequently a higher survival rate was obtained in the following experimental groups: (a) (CY 200 mg/kg, Days 0 and 1) + BMT greater than (CY 400 mg/kg, Day 0) + BMT, (ACNU 20 mg/kg, Days 0 and 1) + BMT greater than (ACNU 40 mg/kg, Day 0) + BMT. (b) (CY 200 mg/kg + ACNU 20 mg/kg, Day 0) + BMT greater than (CY 400 mg/kg or ACNU 40 mg/kg, Day 0) + BMT. (c) (CY 200 mg/kg, Day 0) + (ACNU 20 mg/kg, Day 1) + BMT greater than (ACNU 20 mg/kg, Day 0) + (CY 200 mg/kg, Day 1) + BMT. Among the six anticancer drugs tested in this study, CY and ACNU were suggested to be more appropriate drugs for high-dose chemotherapy-BMT, but methods for reducing drug toxicity (dose, combination, sequence) were necessary so as to enhance the beneficial effect of the BMT.

Animals↗
PubMed1987

[Potentiation of the cytotoxic effects of anticancer drugs on human genitourinary neoplastic cells by recombinant gamma-interferon].

Experiments were performed to ascertain whether or not the cytotoxic effects of various anticancer drugs on five human genitourinary malignant cell lines would be enhanced by recombinant gamma-type interferon. The cells used were as follows: HeLa cells from a uterine cervix cancer, HT-1376 and EJ cells from bladder cancers, ACHN cells from a renal cancer, and PC-3 cells from a prostatic cancer. The effects of the drugs were studied by colony formation assay. The following drugs were used: two metabolic antagonists. cytosine arabinoside (Ara-C) and 5-fluorouracil (5-FU), three antibiotics: adriamycin (ADM), mitomycin C (MMC) and peplomycin (PEP), two alkylating agents: nimustine hydrochloride (ACNU) and melphalan, one vinca alkaloid: vincristine (VCR) and one other drug: cisplatin (CDDP). Interferon used was a preparation of recombinant gamma-type interferon. PEP showed synergistically enhanced cytotoxic effects on HeLa, EJ, HT-1376, and ACHN cells by concomitant application with gamma-IFN. Synergistic cytotoxicity was also detected against HeLa, EJ and ACHN by combined treatment with ADM and gamma-IFN. A similar enhanced cytotoxicity was demonstrated in HT-1376 and PC-3 by 5-FU treatment with gamma-IFN. MMC showed enhanced cytotoxicity only against ACHN cells in the presence of gamma-IFN. The cytotoxic effects of PEP on cells were increased by lower concentrations of gamma-IFN compared with those of other drugs. DNA, RNA and protein synthesis were examined in HeLa cells following combined exposure to PEP and gamma-IFN. The combined therapy was found to produce a specific decrease in DNA synthesis, while yielding no significant inhibition of intracellular RNA and protein synthesis.

Antineoplastic Agents↗
PubMed1988

[Multidisciplinary treatment of advanced neuroblastoma--experience in treatment with the protocol of a group study supported by a grant from Ministry of Health and Welfare].

Ten patients in stages III or IV of neuroblastoma have been receiving treatment on the basis of a group study protocol that is supported by grant from the Ministry of Health and Welfare. Their chemotherapy regimen has consisted of a combination of cyclophosphamide, vincristine, THP-adriamycin, cisplatin, nimustine and dacarbazine. Surgery has been performed on all patients and in 7 patients their primary tumors were resected either as a delayed primary operation or a second look operation. Radiotherapy has been used for four patients at a total dose of 22-40 Gy. Six patients still survive (survival time: 5-27 months) with time spans that have ranged from 2-19 months of complete response. Major complications have been renal insufficiency, hearing loss, cardiac insufficiency, and bone marrow suppression, We focus mainly on the problems of this multidisciplinary treatment protocol.

Adrenal Gland Neoplasms↗
PubMed1988

[AUFRAP therapy: combined modality treatment of malignant gliomas with intraarterial infusion of ACNU].

A method of combination therapy was proposed for the treatment of malignant gliomas, and the clinical results were reported. This combination consisted of ACNU (nimustine), UFT (tegafur + uracil), Radiation, vitamin A and PSK (krestin), and was named AUFRAP therapy. Intracarotid infusion of ACNU (100 or 150 mg/body) was done after the administration of vitamin A (100,000 units), in the first and last week of radiation therapy with a total dose of 60-70 Gy. UFT (400-600 mg/day) and PSK (3g/day) were also given orally. After the induction of remission, patients were treated in the outpatient clinic under a similar maintaining protocol. Two patients who received 150 mg of ACNU and daily 600 mg of UFT in combination with radiation therapy showed severe myelosuppression in the early stage of treatment, and the combination therapy was aborted. Two of four patients who received 100mg of ACNU and daily 400mg of UFT did not show such severe side effects and two showed transient, moderate myelosuppression and vomiting. The serum phenitoin concentration doubled and was thought to be a side effect of tegafur. All four patients completed the induction protocol and follow-up CT scans disclosed shrinkage of the remained tumors, decreased contrast enhancement or no evidence of recurrence. Interactions of these drugs and radiation were discussed and the literature was reviewed.

Adult↗
PubMed1987

[Intrathecal ACNU for the treatment of a meningeal gliomatosis model].

A nitrosourea derivative, ACNU (nimustine hydrochloride), is often used in the chemotherapy of brain tumors and shows considerable efficacy, since it crosses the blood-brain barrier (B.B.B.). This drug is also considered to be useful for intrathecal treatment of meningeal gliomatosis (MG) because of its short half-life in the blood or cerebrospinal fluid (CSF) and its strong cytotoxicity for glioma cells. In order to evaluate the efficacy of intrathecal therapy of MG with ACNU, MG models, which were produced by intracisternal inoculation of rat C6 glioma, were treated with intrathecal or intravenous administration of ACNU. When intrathecally administered 1 day or 3 days after tumor inoculation, ACNU (1 mg/kg) significantly prolonged the survival time of MG rats, where ILS was 35.7 to 42.9% and 24.1 to 25.0%, respectively. In MG rats which were treated intrathecally with ACNU (1 mg/kg) 5 days after tumor inoculation or intravenously with ACNU (15 mg/kg), ACNU failed to prolong survival time compared with the controls. It might therefore be suggested that intrathecal chemotherapy with a low dose of ACNU is effective in the early stages of MG, in which intravenous treatment with a high dose of ACNU is ineffective.

Animals↗
PubMed1986

[Intrathecal ACNU against malignant leptomeningeal tumors--toxicity and therapeutic effect in experimental animals].

Leptomeningeal dissemination is one of the major causes which increase the morbidity and mortality of the patients with malignant brain tumors. The incidence of this complication is increasing, however, no sufficient treatment is available at present. Therefore, in an attempt to establish a new treatment, we studied toxicity and therapeutic effect of intrathecal ACNU (nimustine hydrochloride) using experimental animals. Systemic and local toxicity was tested in normal rats that received ACNU intracisternally. The animals given ACNU more than 3.0 mg/kg progressively lost their body weight, and ACNU 6.0 mg/kg was fatal in 80% of animals. Animals given ACNU less than 1.5 mg/kg gained weight in the same rate as in control animals. Increased capillary permeability to intravenous Evans blue was observed in the subpial region of the brain in the rats given ACNU 6.0 mg/kg intracisternally. The increase of capillary permeability was dominant along the ambient cistern, hypocampal fissure, and at the base of the brain. Demyelinization and loss of neurons were seen in the same areas as well. These changes were not observed in the animal given ACNU less than 1.5 mg/kg. Therapeutic effect of intrathecal ACNU against the leptomeningeal tumor was studied in rats with meningeal carcinomatosis which was induced by intracisternal inoculation of 1 X 10(4) cells of Walker 256 carcinosarcoma. The median survival times of the animal given ACNU 1.5 mg/kg intrathecally on day 2 or 5 after tumor inoculation were prolonged by 55 to 64%, and 64 to 145%, respectively, as compared to those of untreated control animals (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

[Effects of anticancer drugs on multicellular spheroid of 9L rat brain tumor].

The effects of the anticancer drugs Nimustine (ACNU), Aclacinomycin A (ACR), Adriamycin (ADM), Bleomycin (BLM), Cisplatin (CDDP), and 5-Fluorouracil (5-FU) on the multicellular spheroid of a chemically-induced 9L rat glioma was studied. The multicellular spheroid in which cells grow in vitro as three-dimensional aggregates represents a biological model, which is intermediate between monolayer cells in vitro and solid tumors. Spheroids were initiated in bacteriological grade petri dishes seeded with 10(6) 9L rat glioma cells, cultured for four days and thereafter transferred and further developed in a spinner flask. Spheroids of 200-400 micron diameter were sorted and exposed for 24 hours to 5-FU and one hour for other drugs. After treatment both cytotoxic effect and growth delay were analyzed. Following disaggregation using collagenase, pronase and DNAase, cytotoxic effect on multicellular spheroids was measured by colony forming assay and were compared with those effects on 9L monolayer culture cells in the exponential growth. For growth delay assay, multicellular spheroids were individually transferred to 16 mm well containing 0.4 ml agarose base and 2 ml culture medium. Spheroid size was measured twice a week and growth curves were drawn. The growth delay was determined as the treated group vs. control differences in time required to a size four times that of the initial volume. For cells both in the monolayer culture and the multicellular spheroid, the dose response curve for ADM, BLM and 5-FU was "biphasic" and that for ACNU, ACR and CDDP "shoulder-threshold" type.(ABSTRACT TRUNCATED AT 250 WORDS)

Aclarubicin↗
PubMed1983

[Effects of a combination chemotherapy "VEMA" consisting of vincristine, cyclophosphamide, methotrexate and ACNU in the treatment of small cell bronchogenic carcinoma].

A combination chemotherapy "VEMA" consisting of vincristine (VCR), cyclophosphamide (Endoxan, EX), methotrexate (MTX) and nimustine (ACNU) has been carried out for the treatment of small cell bronchogenic carcinoma since September, 1978. "VEMA" regimen consists of VCR 1.3 mg/m2 iv push on day 1, EX 500 mg/m2 iv infusion on day 1 and 2, MTX 28 mg/m2 iv push on day 1, 2 and 3, and ACNU 67 mg/m2 iv push on day 3. This dose schedule was repeated every 3 to 4 weeks. The regimen was given to 14 patients and 12 patients were evaluable. In the 12 evaluable cases, 2 case of complete response (CR), 7 cases of partial response (PR) and 2 cases of effusion effective were obtained. Response rate of CR + PR was 90%. Response rate including CR, PR and effusion effective was 91.7%. The major clinical toxicity of "VEMA" therapy was bone marrow suppression. Other side effects were anorexia, nausea, vomiting, alopecia and stomatitis: etc; however, these side effects were not life threatening to terminate "VEMA" therapy. In conclusion, "VEMA" regimen is a new potent combination chemotherapy in the treatment of small cell bronchogenic carcinoma.

Adult↗
PubMed1984

[Antitumor effect of FU-O-G, new antitumor agent, following long term administration].

FU-O-G, the O-glucuronide methylester of 5-fluorouracil (5-FU), is a compound with a unique chemical structure. It is an antitumor agent of the prodrug type which exerts its activity by enzymatically liberating 5-FU in tumor tissues. It has been reported that the antitumor activity of this compound is superior to those of 5-FU and Tegafur (FT-207) in the treatment of various transplantable tumors. In this study, long-term administration of FU-O-G to mice bearing relatively slow-growing tumors such as Lewis lung carcinoma, mammary tumor FM3 A and hepatoma MH-134 was carried out. Consequently, FU-O-G was shown to be remarkably effective against those tumors, whereas 5-FU and FT-207 were hardly effective. Long-term daily administration was shown to be more effective than intermittent dosage in the treatment of Lewis lung carcinoma. In combination therapies of FU-O-G with other antitumor drugs, FU-O-G exhibited a synergistic effect against Lewis lung carcinoma when combined with Carboquone (CQ) or Nimustine hydrochloride (ACNU).

Animals↗