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Biomedical subjects

Masahiro Hiraoka

Publications and source records attributed to Masahiro Hiraoka.

At least 19 recordsLinked to original sources

Avascular necrosis of bilateral femoral head as a result of long-term steroid administration for radiation pneumonitis after tangential irradiation of the breast.

We report a patient with avascular necrosis of the bilateral femoral head resulting from long-term steroid administration for radiation pneumonitis that occurred after tangential irradiation of the breast. The patient was a 50-year-old postmenopausal woman with breast cancer, stage IIIB (T4bN0M0) in the right C area. Following wide excision of right breast carcinoma and level III axillary lymph node dissection, whole-breast X-ray irradiation was given, at a dose of 2 Gy per fraction; the total dose was 50 Gy. On day 84 after the initiation of radiation therapy, she developed radiation pneumonitis. As the lung shadow expanded to the contralateral lung, she received steroid medication. Despite the steroid medication, the symptoms were exacerbated; therefore, she underwent steroid pulse administration with subsequent oral steroid medication. She improved immediately, but subsequently the radiation pneumonitis relapsed three times when the steroid medication was stopped. The period of medication was 423 days and the cumulative amount of steroids was 7365 mg before complete resolution occurred. In the 19 months after she stopped the steroid administration, she developed avascular necrosis (AVN) of the bilateral femoral head. This was regarded as a complication of the steroid treatment. Patients treated with long-term or high-dose steroid administration have been suggested to be at great risk of developing AVN, but this hypothesis remains controversial. The probability of AVN occurrence may be very small, but it should be considered as one of the complications of steroids, which are often used to treat radiation pneumonitis.

Axilla↗

Vertebrate POLQ and POLbeta cooperate in base excision repair of oxidative DNA damage.

Base excision repair (BER) plays an essential role in protecting cells from mutagenic base damage caused by oxidative stress, hydrolysis, and environmental factors. POLQ is a DNA polymerase, which appears to be involved in translesion DNA synthesis (TLS) past base damage. We disrupted POLQ, and its homologs HEL308 and POLN in chicken DT40 cells, and also created polq/hel308 and polq/poln double mutants. We found that POLQ-deficient mutants exhibit hypersensitivity to oxidative base damage induced by H(2)O(2), but not to UV or cisplatin. Surprisingly, this phenotype was synergistically increased by concomitant deletion of the major BER polymerase, POLbeta. Moreover, extracts from a polq null mutant cell line show reduced BER activity, and POLQ, like POLbeta, accumulated rapidly at sites of base damage. Accordingly, POLQ and POLbeta share an overlapping function in the repair of oxidative base damage. Taken together, these results suggest a role for vertebrate POLQ in BER.

Animals↗

Dosimetric verification in participating institutions in a stereotactic body radiotherapy trial for stage I non-small cell lung cancer: Japan clinical oncology group trial (JCOG0403).

A multicentre phase II trial of stereotactic body radiotherapy for T1N0M0 non-small cell lung cancer was initiated in Japan as the Japan Clinical Oncology Group trial (JCOG0403). Before starting the trial, a decision was made to evaluate the treatment machine and treatment planning in participating institutions to minimize the variations of the prescription dose between the institutions. We visited the 16 participating institutions and examined the absolute dose at the centre of a simulated spherical tumour of 3.0 cm diameter in the lung using the radiation treatment planning systems in each institution. A lung phantom for stereotactic body radiotherapy (SBRT) was developed and used for the treatment planning and film dosimetry. In the JCOG radiotherapy study group, the no model-based calculation algorithm or the model-based calculation algorithm with a dose kernel unscaled for heterogeneities were selected for use in the initial SBRT trials started in 2004, and the model-based calculation algorithm with a dose kernel scaled for heterogeneities was selected for the coming trial. The findings of this study suggest that the clinical results of lung SBRT trials should be carefully evaluated in comparison with the actual dose given to patients.

Algorithms↗

Mechanism of hypoxia-specific cytotoxicity of procaspase-3 fused with a VHL-mediated protein destruction motif of HIF-1alpha containing Pro564.

Under normoxic conditions the alpha-subunit of hypoxia-inducible factor (HIF-1alpha) protein is targeted for degradation by the von Hippel-Lindau (VHL) tumor suppressor protein acting as an E3 ubiquitin ligase. Recently, we developed a hypoxia-targeting protein, TOP3, which consisted of procaspase-3 with the VHL-mediated protein destruction motif of HIF-1alpha. This design enables procaspase-3 to be regulated similarly with HIF-1alpha, being degraded under normoxia while stabilized under hypoxia. Furthermore, stabilized TOP3 was cleaved by the hypoxic stress-induced endogenous caspases and thus the procaspase-3 was converted to active caspase-3 specifically under hypoxic conditions. These data demonstrated that the VHL-mediated protein destruction motif of HIF-1alpha endowed procaspase-3 with hypoxia-specific cytotoxicity.

Amino Acid Motifs↗

Development of a four-dimensional image-guided radiotherapy system with a gimbaled X-ray head.

PURPOSE: To develop and evaluate a new four-dimensional image-guided radiotherapy system, which enables precise setup, real-time tumor tracking, and pursuit irradiation. METHODS AND MATERIALS: The system has an innovative gimbaled X-ray head that enables small-angle (+/-2.4 degrees ) rotations (pan and tilt) along the two orthogonal gimbals. This design provides for both accurate beam positioning at the isocenter by actively compensating for mechanical distortion and quick pursuit of the target. The X-ray head is composed of an ultralight C-band linear accelerator and a multileaf collimator. The gimbaled X-ray head is mounted on a rigid O-ring structure with an on-board imaging subsystem composed of two sets of kilovoltage X-ray tubes and flat panel detectors, which provides a pair of radiographs, cone beam computed tomography images useful for image guided setup, and real-time fluoroscopic monitoring for pursuit irradiation. RESULTS: The root mean square accuracy of the static beam positioning was 0.1 mm for 360 degrees of O-ring rotation. The dynamic beam response and positioning accuracy was +/-0.6 mm for a 0.75 Hz, 40-mm stroke and +/-0.4 mm for a 2.0 Hz, 8-mm stroke. The quality of the images was encouraging for using the tomography-based setup. Fluoroscopic images were sufficient for monitoring and tracking lung tumors. CONCLUSIONS: Key functions and capabilities of our new system are very promising for precise image-guided setup and for tracking and pursuit irradiation of a moving target.

Equipment Design↗

Urinary creatinine excretion and protein/creatinine ratios vary by body size and gender in children.

Urinary protein/creatinine ratio (Up/cr) is a simple measurement for evaluation of proteinuria. However, exact effects of body size and gender on urinary excretion of creatinine and Up/cr remain unknown. We aimed to clarify their effects. Early morning urine samples were collected from 124 children with urinary tract disorders. Urinary hourly excretion of creatinine, Ucr (in milligrams per hour), urinary hourly excretion of protein per body surface area, Up (milligrams per square meter per hour), and Up/cr (milligrams per milligram) were calculated. Effects of gender, age, body height, body weight and body surface area on Ucr and Up/cr were analyzed, respectively, in a multiple linear regression model. Body surface area and gender affected Ucr (r2=0.842, P<0.0001). Ucr adjusted by body surface area increased as body surface area grew with moderate variation. Up/cr showed a close correlation with Up and was affected by body height and gender as well. The regression equation showed that Up/cr values corresponding to the normal upper limit of Up, i.e., 4 mg/m2/h, in boys and girls 170 cm tall were approximately one third of those in children 80 cm tall (0.121 vs 0.043 for boys, 0.132 vs 0.047 for girls). The present study indicates that estimation of Up/cr needs to include consideration of children's body height and gender.

Adolescent↗

Diffusion-tensor fiber tractography: intraindividual comparison of 3.0-T and 1.5-T MR imaging.

PURPOSE: To prospectively evaluate the depiction of brain fiber tracts at 3.0- versus 1.5-T diffusion-tensor (DT) fiber tractography performed with parallel imaging. MATERIALS AND METHODS: Institutional review board approval was obtained, and each subject provided written informed consent. Subjects were 30 healthy volunteers (15 men, 15 women; mean age, 28 years; age range, 21-46 years). Single-shot spin-echo echo-planar magnetic resonance (MR) sequences with parallel imaging were applied. Four fiber tracts were reconstructed: corticospinal tract (CST), superior longitudinal fasciculus (SLF), corpus callosum (CC), and fornix. Two neuroradiologists compared 3.0- and 1.5-T tractography in terms of fiber tract depiction by using five depiction scores (scores 0-4) and numbers of reconstructed tract fibers and in terms of lateral asymmetry in the CST by using numbers of reconstructed fibers. The Wilcoxon signed rank test was applied for statistical analysis. RESULTS: Visual scores for both CST hemispheres (P < .001), the right SLF (P = .005), the CC (P = .01), and the right fornix (P = .04) were higher at 3.0-T DT tractography. Larger numbers of CST (right, P = .008; left, P < .001), SLF (right, P = .001; left, P = .02), and fornix (bilaterally, P = .02) tract fibers were depicted at 3.0 T. The asymmetry index for the CST was lower (P < .001) at 3.0 T. Visual scores for the left SLF and the left fornix and numbers of CC tract fibers were not significantly different. CONCLUSION: Depiction of most fiber tracts was improved at 3.0-T DT tractography compared with depiction at 1.5-T tractography.

Adult↗

Results of radiation therapy combined with neoadjuvant hormonal therapy for stage III prostate cancer: comparison of two different definitions of PSA failure.

BACKGROUND: We herein report the clinical outcome of radical radiation therapy combined with neoadjuvant hormonal therapy (NHT) for stage III (International Union Against Cancer [UICC] 1997: UICC 97) prostate cancer. Prostate-specific antigen (PSA) failure-free survival was assessed according to two different definitions, and the appropriateness of each definition is discussed. METHODS: Between October 1997 and December 2000, 27 patients with stage III prostate cancer were enrolled in this study. The median pretreatment PSA level was 29 ng/ml (range, 7.4-430 ng/ml). The Gleason score (GS) was 7 or more in 22 patients (81%). All patients received 3 months of NHT with a luteinizing hormone-releasing hormone (LH-RH) analogue, in combination with an antiandrogen (flutamide), given during the first 2 weeks, followed by 70-Gy external-beam radiation therapy (EBRT) in 35 fractions. The initial 46 Gy was given with a four-field technique, while the remainder was given with a dynamic conformal technique. No adjuvant hormonal therapy (AHT) was given. RESULTS: The median follow-up time was 63 months. PSA levels decreased to the normal range (<4 ng/ml) after irradiation in all but one patient. The 5-year PSA failure-free survival was 34.8% according to the American Society for Therapeutic Radiology and Oncology (ASTRO) definition and it was 43.0% according to the "nadir plus 2" definition. Discordance of the results between the two definitions was seen in two patients. The 5-year overall and cause-specific survivals were 83.0% and 93.3%, respectively. No severe acute or late adverse effects were observed. CONCLUSION: Seventy Gy of EBRT following 3 months of NHT produced therapeutic results comparable to those reported in other studies which used long-term AHT. The value of long-term AHT for Japanese men should be tested in a clinical trial.

Adenocarcinoma↗

Enzymatic preparation of hollow magnetite microspheres for hyperthermic treatment of cancer.

Ferrimagnetic materials can be expected to be useful as thermal seeds for hyperthermic treatment of cancer, especially where the cancer is located in deep parts of body, as they can generate heat by magnetic hysteretic loss when they are placed in an alternating magnetic field. In this study, hollow magnetite (Fe(3)O(4)) particles were prepared using an enzymatic reaction of urease. A hollow particle was obtained by using a Pasteur pipette. The particle was 500 microm in size and was composed of Fe(3)O(4). Its saturation magnetization and coercive force were 57 emuxg(-1) and 183 Oe, respectively. Its heat generation under an alternating magnetic field of 300 Oe at 100 kHz was estimated to be 45 Wxg(-1). Microspheres 30 microm in diameter were also successfully obtained by using a spray gun.

Biocompatible Materials↗

Initial experiences of palliative stereotactic radiosurgery for recurrent brain lymphomas.

In Kyoto University Hospital, stereotactic radiosurgery (SRS) has been performed for its rapid palliative effect in patients with recurrent primary central nervous system lymphoma (PCNSL), often in combination with salvage chemotherapy. In the present study, the treatment outcome and toxicity of SRS for recurrent PCNSL was retrospectively evaluated. Between March 1998 and June 2004, 17 histologically proven recurrent PCNSLs in nine patients were treated with linac-based stereotactic radiosurgery. All patients had developed intracranial recurrences after initial treatment including external beam radiation therapy (EBRT). The prescribed dose was 10.0-16.0 (median 12.0) Gy. Seven of nine patients received systemic chemotherapy around the time of SRS. The target volume was 0.4-24.5 ml (median 3.5 ml). Initial tumor response could be evaluated in 15 of 17 lesions. Among them, radiological complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) was observed in 3, 10, 2, and 0 lesions, respectively. One-year overall survival rate and relapse-free survival rate after first SRS was 58% and 22%, respectively. Improvement of symptoms was observed in six patients. The time from SRS to symptomatic relief was 1-57 days (median 3 days). No > or = grade 2 acute toxicities related to SRS were observed. In conclusion, linac-based SRS with a prescription dose of 10-12 Gy for recurrent PCNSL is useful for palliation, especially considering the short time, rapid tumor response, and low treatment toxicity.

Aged↗

Suppression of VEGF transcription in renal cell carcinoma cells by pyrrole-imidazole hairpin polyamides targeting the hypoxia responsive element.

Hypoxia inducible factor (HIF), a master regulator of critical genes for cell survival under hypoxic conditions, is known to be related to tumorigenesis and progression of renal cell carcinoma. N-methylpyrrole (Py)-N-methylimidazole (Im) hairpin polyamides are synthetic organic compounds that recognize and bind to the minor grooves of specific DNA sequences. We synthesized three Py-Im hairpin polyamides targeting the flanking sequences of hypoxia responsive element (HRE; a binding site of HIF) in the promoter region of the vascular endothelial growth factor (VEGF) gene. The effects of the polyamides on HIF-induced transcription were evaluated by a luciferase assay using a reporter plasmid containing a VEGF promoter. Real time reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay were performed to examine the effects of the polyamides on the transcription and secretion of VEGF in A498 renal cell carcinoma cells, which have a frame-shift mutation in the von Hippel-Lindau gene. A combination of three Py-Im hairpin polyamides suppressed HIF-induced transcription in reporter assays using 293 cells and successfully suppressed transcription and translation of the VEGF gene in A498 cells. Inhibition of the HIF-HRE interaction was confirmed by an electrophoresis mobility shift assay. An approach using Py-Im hairpin polyamides may be a new strategy for the treatment of renal cell carcinoma.

Base Sequence↗

Evaluation of primary brain tumors with FLT-PET: usefulness and limitations.

PURPOSE OF THE REPORT: The purpose of this report was to investigate the potential of positron emission tomography using F-18 fluorodeoxythymidine (FLT-PET) in evaluating primary brain tumors. MATERIALS AND METHODS: FLT-PET was performed in 25 patients with primary brain tumors. FLT uptake in the lesion was semiquantitatively evaluated by measuring the maximal standardized uptake value (SUVmax) and the tumor-to-normal tissue ratio (TNR). SUVmax and TNR were compared with the histologic grade and the expression of the proliferation marker (Ki-67). RESULTS: FLT uptake in normal brain parenchyma was very low, resulting in the visualization of brain tumors with high contrast. Both SUVmax and TNR significantly correlated with the malignant grade of brain gliomas, in which high SUVmax/TNR was obtained for high-grade gliomas. Patients with primary lymphoma also showed SUVmax/TNR equivalent to glioblastoma. There was a positive correlation between SUVmax/TNR and the Ki-67 index. In contrast, spuriously high SUVmax and TNR were obtained in 3 of 6 patients with suspected recurrent tumors (2 patients with recurrent grade 2 glioma and one patient with postoperative granuloma), all of which showed lesion enhancement on MRI after Gd administration. CONCLUSIONS: FLT-PET can be used to evaluate the malignant grade and proliferation activity of primary brain tumors, especially malignant brain tumors. However, the presence of benign lesions showing blood-brain barrier disruption cannot be distinguished from malignant tumors and needs to be carefully evaluated.

Adolescent↗

Radiofrequency ablation for small hepatocellular carcinoma: prospective comparison of internally cooled electrode and expandable electrode.

PURPOSE: To prospectively compare the effectiveness of radiofrequency (RF) ablation performed by using an internally cooled electrode and an expandable electrode for the treatment of small (< or = 3.0 cm) hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: The human subjects research review board at the study institution approved the protocol, and each patient provided informed consent. Seventy-four patients (58 men and 16 women; age range, 41-83 years) with 83 HCC nodules 3 cm or smaller were randomly divided into an internally cooled electrode group (38 patients with 41 nodules) and an expandable electrode group (36 patients with 42 nodules). RF ablation was performed by one individual. Primary technique effectiveness and rates of major complications were evaluated between the two groups with the Fisher exact test. Rates of local tumor progression, overall survival, local progression-free survival, and event-free survival were evaluated by using the Kaplan-Meier method. RESULTS: The primary technique effectiveness was 95% in the internally cooled electrode group and 93% in the expandable electrode group (P = .51); rates of major complications were 0% and 2.1% per session (P = .50) and 0% and 2.8% per patient (P = .49), respectively. Rates at 1, 2, and 3 years in the internally cooled electrode group versus the expandable electrode group were as follows: local tumor progression, 12% versus 17%, 20% versus 22%, and 20% versus 22% (P = .72, log-rank test); overall survival, 100% versus 94%, 94% versus 92%, and 94% versus 77% (P = .29, log-rank test); local progression-free survival, 87% versus 78%, 73% versus 66%, and 73% versus 46% (P = .27, log-rank test); and event-free survival, 47% versus 44%, 34% versus 22%, and 34% versus 22% (P = .40, log-rank test). CONCLUSION: On the basis of the study findings, RF ablation with an internally cooled electrode needle and an expandable electrode needle has equivalent effectiveness for the treatment of small HCCs.

Adult↗

Outcome of percutaneous transhepatic venoplasty for hepatic venous outflow obstruction after living donor liver transplantation.

PURPOSE: To evaluate retrospectively the outcome of percutaneous transhepatic venoplasty of hepatic venous outflow obstruction after living donor liver transplantation (LDLT). MATERIALS AND METHODS: The institutional Human Subjects Research Review Board approved the interventional protocol and the retrospective study, for which informed consent was not required. Before treatment, informed consent was obtained from the patient or the patient's parents in all cases. Of 26 consecutive patients (nine male, 17 female; median age, 9 years) suspected of having hepatic venous outflow obstruction after LDLT, 20 patients confirmed to have anastomotic outflow stenosis at percutaneous hepatic venography and manometry underwent venoplasty. Pressure gradients before and after venoplasty were evaluated by using a paired t test. Patients in whom obstruction recurred during follow-up were re-treated with venoplasty with or without expandable metallic stents. Patency was analyzed by using Kaplan-Meier analysis. RESULTS: The initial balloon venoplasty was technically successful in all 20 patients, all of whom had improved clinical findings. The pressure gradient +/- standard deviation was reduced from 14.6 mg Hg +/- 8.6 to 2.2 mg Hg +/- 2.4 (P < .001). Eleven patients had recurrent obstruction and were treated with balloon venoplasty; one of them underwent stent placement, as well as venoplasty. The primary (event-free) patency and 95% confidence interval (CI) at 3, 12, and 60 months after venoplasty were 0.80 (95% CI: 0.62, 0.98), 0.60 (95% CI: 0.38, 0.81), and 0.60 (95% CI: 0.38, 0.81), respectively. The primary assisted patency, maintained with repeated venoplasty and expandable metallic stents, was 1.00 at 60 months. CONCLUSION: Percutaneous venoplasty is an effective treatment for hepatic venous outflow obstruction after LDLT.

Adult↗

Influence of radiation dose rate and lung dose on interstitial pneumonitis after fractionated total body irradiation: acute parotitis may predict interstitial pneumonitis.

This study evaluated patients for the influence of the dose rate and lung dose of fractionated total body irradiation (TBI) in preparation for allogeneic bone marrow transplantation (BMT) on the subsequent development of interstitial pneumonitis (IP). Sixty-six patients at our institute were treated with TBI followed by BMT. All of the patients received a total TBI dose of 12 Gy given in 6 fractions over 3 days and were divided into 3 groups according to the radiation dose rate and lung dose: group A, lung dose of 8 Gy (n = 18); group B, lung dose of 12 Gy at 8 cGy/min (n = 25); and group C, lung dose of 12 Gy at 19 cGy/min (n = 23). The overall survival rate, the cumulative incidence of relapse, and the cumulative incidence of IP were evaluated in relation to various potential indicators of future IP. There were no significant differences in survival and relapse rates between patient group A and combined groups B and C. Clinically significant IP occurred in 13 patients. The cumulative incidence of IP was significantly higher in patients who developed acute parotitis as indicated by either an elevation in the serum amylase level or parotid pain of grade 1 to 2. There was no difference in IP incidence among groups A, B, and C. There was no significant difference in IP incidence between lung dose values of 8 Gy (with lung shielding) and 12 Gy (without lung shielding) and between dose rate values of 8 cGy/min and 19 cGy/ min, at least when TBI was given in 6 fractions. The presence of acute parotitis during or just after TBI may be a predictor of IP.

Adolescent↗

Antitumor protein therapy; application of the protein transduction domain to the development of a protein drug for cancer treatment.

The genomic information obtained through the human genome project has been accelerating the analysis of the functions of various disease relevant genes. The high molecular weight biomolecules, including oligonucleotides, antisense nucleotides, small interference RNA and peptides, as well as genes (cDNA) and proteins, are becoming increasingly important for the development of molecular therapies. However, the potential of such information-rich macromolecules for therapeutic use has been limited by the poor permeability across the lipid bilayer of the cellular plasma membrane. Over the past decade, a unique activity of oligopeptides, known as protein transduction domains (PTDs) or cell penetrating peptides (CPPs), has made it possible to transduce biologically active macromolecules into living cells in vitro by conjugating a PTD to the desired macromolecule. Furthermore, this activity has also enabled the systemic delivery of bioactive macromolecules to all tissues in living animals. However, we are now confronted with the next difficulty delivering the macromolecules specifically to the therapeutic targets in vivo. In this review, we focus on the application of PTD to develop antitumor macromolecules and introduce several representative strategies to discriminate between tumor and normal tissue. In addition, we discuss the unique characteristics of breast cancer, which are expected to facilitate the application of PTD to develop novel protein therapy for breast cancer.

Breast Neoplasms↗

A case of metachronous bilateral breast cancer with bilateral radiation pneumonitis after breast-conserving therapy.

We report a patient with metachronous bilateral breast cancer who has twice developed radiation pneumonitis after breast-conserving therapy for each breast. The patient was a 48-year-old woman, who presented with Stage I right breast cancer. After wide excision of the right breast tumor and dissection of level I axillary lymph nodes, systemic therapy with oral 5-FU and tamoxifen was started. Subsequently, tangential irradiation with a total dose of 50 Gy in 25 fractions was given. Seven months after irradiation, she developed respiratory symptoms and radiation pneumonitis was diagnosed. The symptoms resolved with oral prednisolone. Thirty months after the right breast cancer treatment, Stage I left breast cancer was diagnosed. After wide excision of the left breast tumor and partial removal of the level I axillary lymph nodes, the same oral systemic chemo-hormonal therapy was initiated. Thereafter, tangential irradiation with a total dose of 50 Gy in 25 fractions was given. Four months after irradiation, she developed respiratory symptoms. A chest X-ray showed an area of increased density in the left lung consistent with radiation pneumonitis. The symptoms were mild and they improved spontaneously without medication. Although there is insufficient evidence to justify or withhold whole breast radiation therapy from patients with a history of contralateral breast cancer and radiation pneumonitis, it is essential to discuss the adequacy of whole breast irradiation and the possibility of alternative approaches, such as breast-conserving surgery without irradiation or partial breast irradiation for this rare condition.

Antineoplastic Combined Chemotherapy Protocols↗

Phase II study of nimustine, carboplatin, vincristine, and interferon-beta with radiotherapy for glioblastoma multiforme: experience of the Kyoto Neuro-Oncology Group.

OBJECT: This Phase II study was performed to determine the safety, tolerability, and efficacy of combining nimustine (ACNU)-carboplatin-vincristine-Interferon-beta (IFNbeta) chemotherapy. METHODS: Ninety-seven patients with Karnofsky Performance Scale scores of 50 or greater were enrolled in the study. Nimustine (60 mg/m2), carboplatin (110 mg/m2), vincristine (0.6 mg/m2), and IFNbeta (10 microg) were administered on Day 1 concomitant with radiotherapy (63 Gy); vincristine (0.6 mg/m2) and IFNbeta (10 microg) on Days 8 and 15; and IFNbeta alone (10 microg) three times per week throughout the course of radiotherapy. Fifty-six days after radiotherapy ended, the time schedule for chemotherapy was reset and ACNU, carboplatin, vincristine, and IFNbeta were again administered on the new Day 1 and vincristine and IFNbeta on the new Days 8 and 15. This course was repeated every 56 days. Instances of nonhematological toxicity were rare and mild. During the course of radiotherapy, the percentages of patients who experienced Grade 3 toxicity were 14% with neurocytopenia and 7% with thrombocytopenia. Seven percent of all adjuvant chemotherapy cycles following radiotherapy were associated with Grade 3 toxicity, as manifested in neurocytopenia or thrombocytopenia. No instance of Grade 4 toxicity was observed. The median duration of progression-free survival was 10 months (95% confidence interval [CI] 8-12 months) and the median duration of overall survival was 16 months (95% CI 13-20 months). CONCLUSIONS: The combination of ACNU-carboplatin-vincristine-IFNbeta chemotherapy and radiotherapy is safe and well tolerated, and may prolong survival in patients with glioblastoma multiforme.

Adult↗