Malignant gliomas treated with split course radiotherapy plus chemotherapy

Twenty-five adult patients with supratentorial malignant gliomas (malignant astrocytoma and glioblastoma multiforme) verified histologically from 1979 to 1986 postoperatively received combined modalities of split course radiotherapy (sRT), nimustine hydrochloride (ACNU), and tegafur (FT). The initial course of radiation consisted of 30 Gy whole brain in 15 fractions five days a week. After a one-week interruption, local radiation with a limited field including a tumor and a margin was boosted to a total dose of about 50-60 Gy. The results were compared with historical control comprising malignant gliomas which received continuous course of radiotherapy (cRT) with or without other chemotherapy before 1979 and after 1986. The median survival time (MST) of malignant gliomas was 18 months for sRT plus chemotherapy, 12 months for cRT alone, and 13 months for cRT plus chemotherapy. No differences between the Kaplan-Meier survival curves were significant by the generalized Wilcoxon test. Tumor histology, Karnofsky performance status, and patient age related well with survival.     

Combined postoperative radiotherapy and chemotherapy for malignant gliomas

A retrospective analysis was performed on 70 patients with malignant supratentrial astrocytic gliomas (astrocytoma Grade III or glioblastoma multiforme) treated with radiotherapy combined with vincristine (VCR), ACNU and PS-K. From January 1979 through December 1983, 27 patients were treated with treatment protocol A (group A). Protocol A was as follows: (1) total dose of 50 to 65 Gy radiation was given after surgery; (2) radiation plus combination VCR (0.02 mg/kg IV on 1st and 29th day of radiation) and ACNU (2 mg/kg IV 24 hrs after VCR) (3) after synchronized radiotherapy, ACNU (2 mg/kg IV every 6 or 8 weeks) and PS-K (3 or 6 g PO every day). Other 43 patients were treated with treatment protocol B (group B) from January 1984 through June 1988. Protocol B was as follows: (1) radiation dose was same as protocol A; (2) radiation plus combination VCR (0.02 mg/kg IV one day before radiotherapy) and ACNU (2 mg/kg IV on 1st and 1 mg/kg IV on 7, 21, 35th day, 1 hour before radiotherapy) (3) maintenance chemotherapy was same as protocol A. The difference between protocol A and protocol B was based on treatment schedule of ACNU. The characteristics of all patients were studied and identified, mainly age, histologic type, initial performance status, extent of tumor resection, maintenance chemotherapy. The reduction rate of tumor volume was 46.7% in the A group and 49.9% in the B group (not significant). The survival rates at 1, 2 and 3 years after surgery were 74.1%, 55.6% and 51.9% respectively for A group, and 80.5%, 42.4%, and 42.4%, respectively for B group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intra arterial chemotherapy with ACNU and radiotherapy in inoperable malignant gliomas

Summary For the non-operable malignant glioma patients, prognosis remains poor, with a survival of 8 months for the glioblastomas (G), and 15 months for anaplastic astrocytomas (AA). 27 histologic proven malignant gliomas (17 AA and 10 G) were treated between April 1991 and June 1992. Median age was 48 years. The therapeutic protocol consisted of three courses of intra arterial chemotherapy (IAC) with ACNU, at intervals of six weeks, and a localised 60 Gy radiotherapy between the first and the second IAC course. 72 courses of IAC were delivered (2,4 per patient). Response rate was 51,8%. Median survival (MS) was 13 months, with a survival rate of 28% at 24 months. For the AA, MS was 21 months, with a survival rate of 37% at 24 months. For the G, median survival was 10 months. Responders were 65 % for AA, 30% for G. Non responders all died before 24 months had relapsed with a MS of 9 months. 54% of responding patients had a 2 years survival. Toxicity were acceptable with 7% of haematological toxicity and a partial loss of visual acuity in 11% of the cases. No chronic neurological sequellae were noted. We compare theses results with two previous trials, concerning inoperable patients, treated by an association of radiotherapy and systemic chemotherapy. Survival seems to be equivalent with HeCNU and with this treatment, but toxicity decreases with ACNU. Early radiotherapy does not increase complications. This treatment can be used for patients with inoperable malignant gliomas.     

The combined effects of multiple chemotherapeutic agents for malignant glioma cells

The prognosis of malignant gliomas remains poor, despite the progress of surgery and radiotherapy. Chemotherapy has been shown to prolong an overall survival, but the benefits are still small. To overcome this situation, the optimal regimen of antineoplastic agents is required. In the present study, we investigated the effect of the association of five chemotherapeutic drugs, including ACNU, CBDCA, CDDP, VCR, and VP-16, on cell survival of U87, YKG1, A172, and U251 human glioma cell lines, using median-effect analysis. A synergistic effect was obtained by treatment involving the association of VP-16 with ACNU or CDDP among the combinations of two drugs, and the association of ACNU, CBDCA, and VP-16 in the combination of three drugs. This preclinical screening using median-effect analysis supports the design of clinical trials by indicating more effective combinations of antineoplastic agents for malignant gliomas.     

A phase II study of radiotherapy after hyperbaric oxygenation combined with interferon-beta and nimustine hydrochloride to treat supratentorial malignant gliomas

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 15min 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.     

Modified optimal fractionation for poor prognosis malignant gliomas: an elusive search

The prognosis of malignant gliomas has not changed much over the last few decades despite refinements in neurosurgical techniques, high-precision radiotherapy, and newer chemotherapeutic agents. The median survival of poor prognosis malignant gliomas (older and/or poor performance status patients) still remains in the range of 6-9 months following maximal safe resection and postoperative conventionally fractionated adjuvant radiotherapy with or without chemotherapy. However, six weeks of daily radiotherapy does seem inappropriate in relation to the short expected survival time in this subset and there is an increasing emphasis on reducing the overall treatment time and the number of hospital visits by such patients. This can be achieved either by accelerated radiotherapy or by hypofractionated radiation, both of which are equivalent to conventional fractionation in terms of palliative effect and survival, as in discussed in this review. Despite enough evidence, such alteration of fractionation has not gained widespread acceptance by the oncologic fraternity. This review has been conducted to collate the evidence that could help shift the paradigm from conventional to modified fractionation in poor prognosis malignant glioma patients.     

Phase I/II clinical trial of carbon ion radiotherapy for malignant gliomas: combined X-ray radiotherapy, chemotherapy, and carbon ion radiotherapy

PURPOSE: To report the results of a Phase I/II clinical trial for patients with malignant gliomas, treated with combined X-ray radiotherapy (XRT), chemotherapy, and carbon ion radiotherapy (CRT). METHODS AND MATERIALS: Between October 1994 and February 2002, 48 patients with histologically confirmed malignant gliomas (16 anaplastic astrocytoma (AA) and 32 glioblastoma multiforme (GBM) were enrolled in a Phase I/II clinical study. The treatment involved the application of 50 Gy/25 fractions/5 weeks of XRT, followed by CRT at 8 fractions/2 weeks. Nimustine hydrochloride (ACNU) were administered at a dose of 100 mg/m(2) concurrently in weeks 1, 4, or 5 of XRT. The carbon ion dose was increased from 16.8 to 24.8 Gray equivalent (GyE) in 10% incremental steps (16.8, 18.4, 20.0, 22.4, and 24.8 GyE, respectively). RESULTS: There was no Grade 3 or higher acute reaction in the brain. The late reactions included four cases of Grade 2 brain morbidity and four cases of Grade 2 brain reaction among 48 cases. The median survival time (MST) of AA patients was 35 months and that of GBM patients 17 months (p = 0.0035). The median progression-free survival and MST of GBM showed 4 and 7 months for the low-dose group, 7 and 19 months for the middle-dose group, and 14 and 26 months for the high-dose group. CONCLUSION: The results of combined therapy using XRT, ACNU chemotherapy, and CRT showed the potential efficacy of CRT for malignant gliomas in terms of the improved survival rate in those patients who received higher carbon doses.     

Proliferative potential and outcome in pediatric astrocytic tumors

Summary In 43 pediatric patients (29 male, 14 female) with primary astrocytic tumors of the central nervous system (CNS), the correlation was evaluated between outcome and proliferative potential, measured by the bromodeoxyuridine (BrdU) labeling index (LI). Twenty-five patients had low-grade gliomas, 13 had anaplastic gliomas, and 5 had glioblastomas multiforme (GBM). All patients underwent surgery; 37 also had chemotherapy, radiation therapy, or both. The median BrdU LIs were < 1% (range 0–9.3%) in low-grade gliomas, 2.3% (range 0–21.2%) in anaplastic gliomas, and 7.7% (range 0–21.3%) in GBM. Seven of eight patients with BrdU LI > 5% have died (median survival 29 weeks). Median survival has not been reached in patients with BrdU LI <1% (19/22 alive) or between 1% and 5% (12/13 alive) after median follow-up periods of 165 and 120 weeks, respectively. A high BrdU LI correlated with short survival (p = 0.0001); the association between malignant histology and short survival was weaker (p = 0.019). BrdU LI is therefore a significant predictor of outcome in patients with primary CNS astrocytomas and appears to be a stronger predictor than histology in patients with low-grade and anaplastic gliomas. More patients need to be studied to confirm these preliminary observations. Address for offprints: M.D. Prados, Department of Neurological Surgery, c/o The Editorial Office, 1360 Ninth Avenue, Suite 210, San Francisco, CA 94122, USA     

Biological basis for combined radio-chemotherapy in radioresistant tumors

Human tumor cells such as melanoma or glioblastoma are intrinsically radioresistant on an average than cells of more common tumors in radiotherapy such as squamous cell carcinoma or adenocarcinoma. Mean inactivation dose (D) for glioblastoma A-7 cells was 3.1 Gy for cells growing exponentially, but was 4.3 Gy for cells grown in large spheroids with hypoxic cells and PLD recovery. The D for cells of squamous cell carcinoma was about 2.1 Gy. This indicates that local control of the radioresistant tumors may be achieved if a drug showing an enhancement ratio of about 2.0. Data on our experiments with others in the literature indicate that drugs which selectively sensitize hypoxic cells and inhibit PLD recovery may be useful to increase the therapeutic ratio. Experimental evidence on a nitrosourea, ACNU has been presented for such mechanisms of the action. Multivariate analysis with Cox's model on malignant gliomas of 209 patients indicated that a significant increase in the survival time was obtained in the radiotherapy combined with ACNU.     

Advances of BRM therapy of malignant brain tumors

The cooperative study on the beta-interferon (IFN) therapy for glioblastoma and malignant astrocytoma reported the response rate as 14.0%. Continuing study resulted the response rate of 24.0% to low grade astrocytoma and 20.0% to medulloblastoma. Totally, effectiveness of 19.2% to gliomas was confirmed in 120 evaluated cases. A randomized study was conducted on combination therapy with beta-interferon and chemoradiotherapy. The response rate of 41.2% (21/51) in the group treated with IFN, ACNU and Radiation was significantly higher than the rate of 19.6% (10/51) in the group treated with ACNU and radiation only. Application of IFN to a maintenance therapy is also on going. Adoptive immunotherapy has been developed as potential therapeutic method of malignant glioma. Lymphokine activated killer cells (LAK) and Tumor infiltrating lymphocytes (TIL) are put to clinical use. Clinical application of human monoclonal antibody (MAb) CLN-IgG was conducted to recurrent malignant glioma. 131I labeled MAb was administered intratumorously and the specific incorporation was confirmed by gamma-scintigraphy. Concomitant administration of interferon enhanced the efficacy of the therapy. This radio-immunotherapy holds future promise as a new therapeutic approach to gliomas.     

Radiotherapy for newly diagnosed malignant glioma in adults: a systematic review.

PURPOSE: A systematic review was conducted to develop guidelines for radiotherapy in adult patients with newly diagnosed malignant glioma.METHODS: MEDLINE, CANCERLIT, the Cochrane Library, and relevant conference proceedings were searched to identify randomized trials and meta-analyses.RESULTS: Pooling of six randomized trials detected a significant survival benefit favouring post-operative radiotherapy compared with no radiotherapy (risk ratio, 0.81; 95% confidence interval, 0.74 to 0.88, P<0.00001). Two randomized trials demonstrated no significant difference in survival rates for whole brain radiation versus more local fields that encompass the enhancing primary plus a 2 cm margin. A randomized trial detected a small improvement in survival with 60 Gy in 30 fractions over 45 Gy in 20 fractions. Radiation dose intensification and radiation sensitizer approaches have not demonstrated superior survival rates compared with conventionally fractionated doses of 50-60 Gy.CONCLUSIONS: Post-operative external beam radiotherapy is recommended as standard therapy for patients with malignant glioma. The high-dose volume should incorporate the enhancing tumour plus a limited margin (e.g. 2 cm) for the planning target volume, and the total dose delivered should be in the range of 50-60 Gy in fraction sizes of 1.8-2.0 Gy. Radiation dose intensification and radiation sensitizer approaches are not recommended as standard care. For patients older than age 70, preliminary data suggest that the same survival benefit can be achieved with less morbidity using a shorter course of radiotherapy. Supportive care alone is a reasonable therapeutic option in patients older than age 70 with a poor performance status.     

Neuro-Oncology Working Group 01 trial of nimustine plus teniposide versus nimustine plus cytarabine chemotherapy in addition to involved-field radiotherapy in the first-line treatment of malignant glioma.

PURPOSE: The role of chemotherapy in the primary treatment of malignant glioma remains controversial. The results from the German-Austrian Glioma trial (GAG, 1983 to 1988) demonstrated a survival benefit for chemotherapy using carmustine (BCNU) plus teniposide (VM26) over BCNU alone in addition to radiotherapy in patients with a Karnofsky performance score (KPS) more than 60. The Neuro-Oncology Working Group (NOA) of the German Cancer Society therefore compared the efficacy of nimustine (ACNU) plus VM26 and ACNU plus cytarabine (Ara-C) chemotherapy in addition to standard radiotherapy in patients with newly diagnosed malignant glioma. PATIENTS AND METHODS: From 1994 to 2000, 375 patients were randomly assigned to receive radiotherapy and cycles of ACNU 90 mg/m2 intravenously (IV) on day 1 and VM26 60 mg/m2 IV on days 1 to 3 (n = 183), or ACNU 90 mg/m2 IV on day 1 and Ara-C 120 mg/m2 IV on days 1 to 3 (n = 179), in 6-week intervals. Thirteen patients were not eligible after central neuropathology review. The remaining 362 patients had glioblastoma (n = 301) or anaplastic glioma (n = 61). RESULTS: Median survival and 2-year survival rates were 17.3 months and 25% for ACNU plus VM26, and 15.7 months and 29% for ACNU plus Ara-C in glioblastoma, and 60 months and 88% for ACNU plus VM26 and 62.5 months and 72% for ACNU plus Ara-C in anaplastic glioma. Multivariate analysis revealed no survival advantage for either arm or for subpopulations defined by histology, age, or KPS. Hematologic toxicity was more prominent in the ACNU plus Ara-C arm. CONCLUSION: The median survival times and 2-year survival rates for patients with anaplastic glioma and glioblastoma achieved in the NOA-01 trial compare favorably with historical trials and with the Radiation Therapy Oncology Group database. The toxicity profile favors ACNU plus VM26 for further evaluation.     

Old but new methods in radiation oncology: hyperbaric oxygen therapy

The presence of hypoxic tumor cells is widely regarded as one of the main reasons behind the failure to control malignant tumors with radiotherapy treatments. Since hyperbaric oxygenation (HBO) improves the oxygen supply to the hypoxic tumor cells, HBO therapy has previously been used in combination with simultaneous radiotherapy to treat malignant tumors. In some clinical trials, significant improvements in local control and survival have been seen in cancers of the head and neck and the uterine cervix. However, the delivery of simultaneous HBO therapy and radiotherapy is both complex and time-consuming, with some trials reporting increased side effects. As a result, the regimen of HBO therapy in combination with simultaneous radiotherapy has yet to be used as a standard treatment for malignant tumors. In recent years, however, radiotherapy immediately after HBO therapy has been emerging as an attractive approach for overcoming hypoxia in cancer treatment. Several studies have reported that radiotherapy immediately after HBO therapy was safe and seemed to be effective in patients with high-grade gliomas. Also, this approach may protect normal tissues from radiation injury. To accurately estimate whether the delivery of radiotherapy immediately after HBO therapy can be beneficial in patients with high-grade gliomas and other cancers, further prospective studies are warranted.     

多西他赛乏氧增敏放射治疗食管癌的临床研究

目的探讨周剂量多西他赛乏氧增敏放射治疗食管癌的临床疗效。方法选择100例乏氧阳性食管癌患者随机分为增敏组50例和单放组50例。两组均行前程普通放疗加后程适形放疗,总剂量DT66～70 Gy/33～35次,6.5-7周完成。增敏组在放疗同期行多西他赛化疗,每次40 mg,每周1次,总量为160～200 mg/4～5次,同时给一定的对症支持治疗。治疗前及治疗后行上消化道造影、胸部CT,腹部B超等检查,以评价疗效。结果增敏组总有效率（CR＋PR）为92%,单放组总有效率为66%,两组差异具有统计学意义（P〈0.05）;两组中位生存时间分别为31月和20月,1、2、3年生存率分别为（89.8±3.7）%（95%可信区间）、（78.1±6.4）%、（38.7±9.1）%和（85.6±3.5）%、（49.8±7.7）%、（15.8±11.5）%。两组比较,1年总生存率（OS）差异无统计学意义（P〉0.05）,2年、3年OS差异有统计学意义（P〈0.05）,两组1、2、3年局部控制率分别为78.9%、52.3%、18.6%和66.1%、32.4%、9.8%,两组比较差异有统计学意义（P〈0.05）。增敏组骨髓抑制毒副反应较单放组增加,但经处理后均能顺利完成治疗。结论周剂量多西他赛乏氧增敏放射治疗食管癌疗效较好,不良反应可以耐受。     

颈动脉灌注尼莫司汀化疗加立体定向适形放疗治疗脑胶质瘤的研究

背景与目的：脑胶质瘤很难经手术彻底切除，术后易复发。本研究探讨经颈动脉灌注尼莫司汀化疗加立体定向适形放疗针对术后脑胶质瘤的临床治疗效果。方法：对35例经手术切除脑胶质瘤的患者，于术后7-21天行颈动脉灌注尼莫司汀1次．每次2．5mg／kg，每个月1次，3次为1个疗程。同时术后第14-28天开始行立体定向适形放疗，约5～6周后结束。术后6个月再根据复查情况决定是否进行第2个疗程治疗。结果：随访6个月至4年，肿瘤消失12例（34．2％），肿瘤明显缩小10例（28．5％），复发经2次手术而且行本方案治疗后肿瘤消失4例（11．4％），病情恶化4例（11．4％），死亡5例（14．2％）。结论：经颈动脉灌注尼莫司汀化疗加立体定向适形放疗对术后脑胶质瘤具有明显的辅助治疗作用。     

脑恶性胶质瘤术后会师化疗同步适形放疗的临床观察

目的 探讨脑恶性胶质瘤显微手术全切后间质内尼莫司汀（ACNU）与替莫唑胺（TMZ）会师化疗同步适形放疗的临床疗效和安全性。方法 选取临床影像诊断为脑恶性胶质瘤的患者99例,均行开颅显微手术全切肿瘤和组织病理证实,术后采用单纯适形放疗( RT) 21 例,采用尼莫司汀间质化疗同步适形放疗( ACNU + RT) 24例,采用替莫唑胺化疗同步适形放疗( TMZ + RT) 23例,ACNU间质内化疗与口服TMZ会师化疗同步适形放疗(ACNU + TMZ + RT) 31例,比较四组的疗效和安全性。结果 脑恶性胶质瘤显微手术全切术后ACNU + TMZ +RT组患者1、2、3年存活率分别为80.6%(25/31)、48.4%(15 /31)、25.8%(8 /31),中位生存时间为29.0（39.8～18.6）月。术后1、2、3年ACNU +TMZ + RT组中位生存时间明显长于RT组、ACNU + RT 组和TMZ + RT 组(χ_L²=21.045和22.385,P=0.043和0.045);脑恶性胶质瘤显微手术全切术后ACNU + TMZ +RT组患者1、2、3年Karnofsky≥60所占比率分别为77.4%(24 /31)、48.4%(15 /31)、22.8%(8 /31)。术后1、2年ACNU+TMZ+RT组生存质量明显优于RT组、ACNU+RT 组及TMZ+RT组(χ²=8.199,P=0.042)、(χ²=7.864,P=0.049)。结论 脑恶性胶质瘤显微手术力争全切除,术后间质内ACNU与TMZ会师化疗同步适形放疗是脑恶性胶质瘤较优化的综合治疗方案,可显著延长患者的生存时间,提高患者的生存质量。     

Treatment outcomes and dose-volume histogram analysis of simultaneous integrated boost method for malignant gliomas using intensity-modulated radiotherapy

Background The aim of this article is to report the treatment outcomes, toxicities, and dosimetric feasibility of our simultaneous-boost intensity-modulated radiotherapy (SIB-IMRT) protocol. Methods Thirteen patients with malignant gliomas treated between December 2000 and September 2004 were enrolled in this study. Two planning target volumes (PTVs) were defined in the present study. Our IMRT regimen delivered 70 Gy/28 fractions (fr)/daily; 2.5 Gy to the gross tumor volume (GTV) with a 0.5-cm margin, defined as the PTV-G, and 56 Gy/28 fr/daily, with 2.0 Gy to the surrounding edema, defined as the planning target volume annulus (PTV-a). Eleven of the 13 patients received one or two courses of nimustine hydrochloride (ACNU) (100 mg/m²) and vincristine (1.2 mg/body) and interferon-β (3 × 10⁶ units) three times weekly during the period of radiotherapy. Adjuvant chemotherapy, ACNU (100 mg/m²) and vincristine (1.2 mg/body), was repeated every 6 weeks and interferon-β was repeated every 2 weeks. The treatment outcomes, toxicity, and dosimetric feasibility were assessed. Results All the patients experienced tumor recurrence. The median progression-free survival times for patients with grade III tumors and glioblastome were 7.5 and 8.0 months, respectively. The 1-year and 2-year overall survival rates for all the patients were 77% and 31%, respectively. Four patients experienced acute grade 1/2 toxicities during the treatment. No late toxicity related to radiotherapy has been seen. Analyses with dose-volume histograms confirmed excellent conformity of dose distributions in the two target volumes, PTV-G and PTV-a, with the sparing of organs at risk. Conclusion Our IMRT regimen did not prevent tumor progression. However, the ability of IMRT to deliver highly conformative doses to two contiguous targets, GTV and the surrounding edema, justifies its application to malignant gliomas.     

Daily Low-dose Carboplatin as a Radiation Sensitizer for Newly Diagnosed Malignant Glioma

Surgical resection followed by local field radiotherapy is currently our most effective approach to treatment for most patients with malignant glioma. Carboplatin chemotherapy has direct cytotoxic effects on glioma cells and acts as a radiation sensitizer to enhance cell killing. Its demonstrated efficacy as a sensitizer in other solid tumors led to this clinical trial of carboplatin as a radiation sensitizer in the treatment of newly diagnosed glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA). Fourteen patients (nine GBM and five AA) were treated with daily low-dose carboplatin 25mg/m² intravenously within 2h of their fractionated radiotherapy to a total dose of 600mg/m². No significant toxicities attributable to this combined therapy were observed. All patients have progressed, with median time to progression of 16 weeks. Eleven patients have died, with median survival of 38 weeks for the entire cohort. Although this regimen appeared safe, there was no benefit in survival time compared to historical patients treated with radiotherapy. The limitations and future potential for the strategy of radiation sensitization are discussed.     

A Phase II Study of Nimustine Hydrochloride,Cisplatin, and Etoposide Combination Chemotherapy for Supratentorial Malignant Gliomas

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 60mg/m²/day for 5 days, respectively, ACNU doses 80mg/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.     

Fast neutron therapy for malignant astrocytomas

The treatment of supratentorial malignant gliomas has continued to be a major problem for neurosurgeons and oncologists. Post-operative conventional radiotherapy is known to prolong survival and to enhance the quality of life. Local persistence of tumor kills the majority of patients. Fast neutron irradiation is being utilized to treat malignant gliomas based on its reputed radiobiological advantages for treatment of large tumors and the encouraging preliminary reports showing tumor eradication in post-radiation biopsy and autopsy specimens. This paper reviews the results of fast neutron irradiation alone and in combination with photons and hypoxic cell sensitizers. Survival comparisons do not show any superiority for neutrons compared to conventional radiation. However, post-neutron radiation tissue samples have shown less agressive and minimal residual tumor in many instances. At the same time radiation necrosis has emerged as a significant problem. In summary, even though neutron irradiation can eradicate malignant gliomas a therapeutic window has yet to be identified. Address for offprints: Neutron Therapy Facility, MS-301, P.O. Box 500, Batavia, IL 60510, USA