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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↗
PubMed1995

[Induction chemotherapy followed by adjuvant surgery (IC-AS) in patients with stage I-II small cell lung cancer (SCLC)].

Ten patients with stage I-II SCLC received IC-AS between 1984 and 1993. As induction chemotherapy, COMP-VAN alternating chemotherapy and CAV-PVP hybrid chemotherapy were administered. The former consisted of a 4-drug combination of cyclophosphamide (CPA), vincristine (VCR), methotrexate (MTX) and procarbazine alternated with a 3-drug combination of etoposide (ETP), adriamycin (ADM) and nimustine every 4 weeks. In the latter, a 3-drug combination of CPA, ADM and VCR given on day 1, and a 2-drug combination of ETP and cisplatin on day 8, were repeated every 4 weeks. All the patients had an objective response, including one complete response by induction chemotherapy. Post-operative pathology revealed SCLC in 4 patients, adenocarcinoma in 2 and no tumor (pathological CR) in 4. Four patients relapsed, and a intrathoracic relapse was experienced in only 2 patients. Six patients have died: 3 from relapsing SCLC, 2 from stomach cancer, and 1 from squamous lung cancer, who was salvaged from relapsing SCLC. The median survival time was 27.5 months, and the 3-year survival rate 37.5%. These results indicate that IC-AS is highly effective for stage I-II SCLC and warrant additional studies comparing IC-AS with chemo-radiotherapy.

Aged↗
PubMed1993

[Specific curative effects of nitrosourea drugs on tumor cells with Mer--phenotype in Chinese].

O6-Methylguanine DNA methyltransferase (O6-MT) activity and cellular sensitivity to nitrosourea drugs of 10 kinds of tumor cell strains derived from Chinese patients were measured by 3H radioactivity and colony-forming ability, respectively. The results in vitro showed that nimustine (Nim) 25 micrograms.ml-1 and carmustine (Car) 20 micrograms.ml-1 exhibited specific killing effects on Mer-phenotype tumor cells characterized by low O6-MT activity. In vivo both Nim and Car (25 mg.kg-1.wk-1 x 4 wk, ip) had specific curative ability to Mer- tumor cells implanted in nude mice. These findings suggested that assay of O6- MT activity in tumor biopsy could be used as a predictable guide to human tumor chemotherapy with nitrosourea compounds.

Animals↗
PubMed1994

[A case of essential thrombocythemia with clonal evolution in the terminal phase].

This 50-year-old male was admitted to the hospital on April 1983 with complaints of severe chest pain attacks 2 weeks previously. Laboratory data: On admission the blood findings were Hb 14.3 Gm/dl of blood, RBC 4.70 million/mm3, WBC 11,600/mm3 and a platelet count of 1.1 million/mm3. ECG showed elevation of ST-T in V1 to V4. Serum LDH and CPK levels were high. He was diagnosed as acute myocardial infarction with thrombocythemia. Three days after admission he abruptly fell into a semicomatose state and left hemiplesia. Head computed tomography showed a large, low-density lesion in the right mid-cerebral artery area, and we also diagnosed cerebral infarction. He was given nimustine (ACNU) 100 mg/week three times as remission induction therapy. For maintenance chemotherapy, at first we administered mitobronitol (DBM) 150 mg/day then changed to intermittent administration of ACNU 100 mg. On September 1991, the patient was admitted to the hospital with progressive anemia and uncontrollable thrombocythemia. Bone marrow chromosome analysis revealed aneuploidy. The patient received interferon alpha 3 million unit/day. The thrombocythemia could be controlled but his general condition deteriorated. On April 1992, he died of interstitial pneumonia.

Aneuploidy↗
PubMed1996

[ACNU and methyl-CCNU in combination chemotherapy for advanced gastric cancer: a randomized comparative study. Shanghai ACNU Collaborative Study Group].

The study was conducted to compare the efficacy between a combined chemotherapy of ACNU (Nimustine hydrochloride, brand name Nidran), a new nitrosourea agent, and a combined chemotherapy of methyl-CCNU for advanced gastric cancer. One hundred and three cases of advanced gastric cancer were randomly allocated into Group A (Me-CCNU, 5-Fu and ADM) and Group B (ACNU, 5-Fu and ADM). The results showed that in Group A there was no CR or PR, while in Group B, although no CR, there were 8 PR (8/64 cases), denoting the response rate of 0% in Group A and 17.4% in Group B. The median survival period in Group A was 108 days and in Group B 112 days. Both groups well tolerated the treatment and there were no serious adverse effects. Quality of life (QOL) was better in Group B than in Group A. It is concluded that ACNU combination is superior to Me-CCNU combination for advanced gastric cancer.

Adenocarcinoma↗
PubMed1997

[Clinical study of primary central nervous system lymphoma: the role of chemotherapy].

We conducted a retrospective study of 32 patients with histologically confirmed primary central nervous system lymphoma treated in our institute between 1971 and 1995 with an emphasis on the role of chemotherapy. Thirty of the 32 patients underwent tumor resection, whereas 2 patients had biopsies only. Twenty-eight patients received adjuvant therapy, 9 of whom received radiation therapy alone, 2 received chemotherapy alone, and 17 received both radiation therapy and chemotherapy. Chemotherapies performed were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone). VEMP or VENP (vincristine, cyclophosphamide, mercaptopurine [or Natulan], and prednisolone), intravenous ACNU (nimustine), and intravenous or intra-arterial MCNU (ranimustine) and CBDCA (carboplatin). Survival data were available for 30 of the 32 patients. The median survival time of this study was 12.5 months. Twenty-seven patients died from one month through 79 months after the initiation of therapy, and 3 patients were alive for 13 to 69 months. Two patients who received the combination of radiation therapy and chemotherapy survived longer than 5 years. Although radiation therapy and chemotherapy were individually both effective and prolonged the survival time, their combination was more effective. The median survival time was significantly shorter (7.0 vs 16.5 months, p < 0.05) for the patients who received radiation therapy alone than for the patients who received the combination of radiation therapy and chemotherapy. We conclude from our results and review of previous studies that it is important for the chemotherapy of primary central nervous system lymphoma 1) to apply a combination of a variety of effective drugs, similar to that for systemic malignant lymphoma, and 2) to make a sufficient amount of anti-cancer drugs penetrate the whole central nervous system, thereby satisfying the adequate dose intensity for each drug.

Adolescent↗