GliaSite Brachytherapy for Treatment of Recurrent Malignant Gliomas:A Retrospective Multi-institutional Analysis

Neurosurgery ◽  
2006 ◽  
Vol 58 (4) ◽  
pp. 701-709 ◽  
Author(s):  
Arash J. Gabayan ◽  
Sylvan B. Green ◽  
Abhay Sanan ◽  
Joseph Jenrette ◽  
Christopher Schultz ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Glioblastoma Multiforme ◽  
Median Survival ◽  
Karnofsky Performance Status ◽  
External Beam Radiotherapy ◽  
Performance Status ◽  
Malignant Gliomas ◽  
Balloon Catheter ◽  
Median Dose ◽  
Karnofsky Performance Status Score

Abstract OBJECTIVE: To review the cumulative experience of 10 institutions in treating recurrent malignant gliomas with the brachytherapy device, GliaSite Radiation Therapy System. METHODS: The patient population consisted of 95 patients with recurrent grade 3 or 4 gliomas, a median age of 51 years, and a median Karnofsky performance status score of 80. All patients had previously undergone resection and had received external beam radiotherapy as part of their initial treatment. After recurrence, each patient underwent maximal surgical debulking of their recurrent lesion and placement of an expandable balloon catheter (GliaSite) in the tumor cavity. The balloon was afterloaded with liquid 125I (Iotrex) to deliver a median dose of 60 Gy to an average depth of 1 cm with a median dose rate of 52.3 Gy/hr. Patients were carefully followed with serial magnetic resonance imaging and monthly examinations for tumor progression, side effects, and survival. RESULTS: The median survival for all patients, measured from date of GliaSite placement, was 36.3 weeks with an estimated 1 year survival of 31.1%. The median survival was 35.9 weeks for patients with an initial diagnosis of glioblastoma multiforme and 43.6 weeks for those with non- glioblastoma multiforme malignant gliomas. Analysis of the influence of various individual prognostic factors on patient survival demonstrated that only Karnofsky performance status significantly predicted for improved survival. There were three cases of pathologically documented radiation necrosis. CONCLUSION: Reirradiation of malignant gliomas with the GliaSite Radiation Therapy System after reresection seems to provide a modest survival benefit above what would be expected from surgery alone. This report not only confirms the initial results of the feasibility study but provides evidence that similar outcomes can be obtained outside of a clinical trial.

Abbreviated Course of Radiation Therapy in Older Patients With Glioblastoma Multiforme: A Prospective Randomized Clinical Trial

2004 ◽  
Vol 22 (9) ◽  
pp. 1583-1588 ◽  
Author(s):  
W. Roa ◽  
P.M.A. Brasher ◽  
G. Bauman ◽  
M. Anthes ◽  
E. Bruera ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Glioblastoma Multiforme ◽  
Older Patients ◽  
Treatment Time ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Wilcoxon Test ◽  
Rank Test ◽  
Survival Times

Purpose To prospectively compare standard radiation therapy (RT) with an abbreviated course of RT in older patients with glioblastoma multiforme (GBM). Patients and Methods One hundred patients with GBM, age 60 years or older, were randomly assigned after surgery to receive either standard RT (60 Gy in 30 fractions over 6 weeks) or a shorter course of RT (40 Gy in 15 fractions over 3 weeks). The primary end point was overall survival. The secondary end points were proportionate survival at 6 months, health-related quality of life (HRQoL), and corticosteroid requirement. HRQoL was assessed using the Karnofsky performance status (KPS) and Functional Assessment of Cancer Therapy-Brain (FACT-Br). Results All patients had died at the time of analysis. Overall survival times measured from randomization were similar at 5.1 months for standard RT versus 5.6 months for the shorter course (log-rank test, P = .57). The survival probabilities at 6 months were also similar at 44.7% for standard RT versus 41.7% for the shorter course (lower-bound 95% CI, −13.7). KPS scores varied markedly but were not significantly different between the two groups (Wilcoxon test, P = .63). Low completion rates of the FACT-Br (45%) precluded meaningful comparisons between the two groups. Of patients completing RT as planned, 49% of patients (standard RT) versus 23% required an increase in posttreatment corticosteroid dosage (χ2 test, P = .02). Conclusion There is no difference in survival between patients receiving standard RT or short-course RT. In view of the similar KPS scores, decreased increment in corticosteroid requirement, and reduced treatment time, the abbreviated course of RT seems to be a reasonable treatment option for older patients with GBM.

scholarly journals Radiosurgery and Accelerated Radiotherapy for Patients with Glioblastoma

1997 ◽  
Vol 24 (2) ◽  
pp. 110-115 ◽  
Author(s):  
G. Shenouda ◽  
L. Souhami ◽  
E.B. Podgorsak ◽  
J.P Bahary ◽  
J.G. . Villemure ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Stereotactic Radiosurgery ◽  
Karnofsky Performance Status ◽  
External Beam Radiotherapy ◽  
Performance Status ◽  
Late Complications ◽  
Accelerated Radiotherapy ◽  
Brain Necrosis ◽  
Steroid Dependent ◽  
Concomitant Boost

ABSTRACT:Objective:To assess the feasibility, toxicity, and local control of stereotactic radiosurgery followed by accelerated external beam radiotherapy (AEBR) for patients with glioblastoma multiforme.Materials and methods:Six males and eight females, with a median age of 67.5 years (range 45-78 years), entered the study. Karnofsky performance status was 90 for five, 80 for six, and 60 for three patients. Following surgery, the patients were left with a residual mass 4 cm. Radiosurgery was delivered with a single dose of 20 Gy to the 90% isodose surface corresponding to the contrast-enhancing edge of the tumour. A total AEBR dose of 60 Gy in 30 fractions was delivered using a concomitant boost technique over four weeks.Results:Median survival time was 40 weeks (range 17-80 weeks). Actuarial survivals at 12 and 18 months were 43% and 14%, respectively. The median time to progression was 25 weeks (range 2-77 weeks). One patient developed a seizure on the day of stereotactic radiosurgery. Two patients experienced somnolence at 47 and 67 days post-radiotherapy. Eight patients remained steroid-dependent. Radiological evidence of leukoencephalopathy was observed in one patient, and brain necrosis in two additional patients at 30 and 63 weeks. One of these two patients with brain necrosis developed complete loss of vision in one eye, and decreased vision in the contralateral eye at 63 weeks.Conclusion:Stereotactic radiosurgery followed by AEBR was feasible but was associated with late complications. The use of such radiosurgical boost for patients with glioblastoma multiforme should be reserved for those patients entering controlled clinical trials.

scholarly journals High Dose Tamoxifen and Radiotherapy in Patients with Glioblastoma Multiforme: A Phase IB Study

2000 ◽  
Vol 27 (4) ◽  
pp. 302-306 ◽  
Author(s):  
Thierry Muanza ◽  
George Shenouda ◽  
Luis Souhami ◽  
Robert Corns ◽  
Richard Leblanc ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Karnofsky Performance Status ◽  
External Beam Radiotherapy ◽  
Performance Status ◽  
Radiation Therapy Oncology Group ◽  
Tumor Resection ◽  
High Dose ◽  
Class Iii ◽  
Actuarial Survival ◽  
Post Surgery

Purpose:To assess the feasibility and the toxicity of adjuvant high dose tamoxifen (TAM) and postoperative brain irradiation for patients with newly-diagnosed glioblastoma multiforme (GBM).Material and Methods:Twelve patients with histopathologically confirmed GBM entered the study. There were nine males and three females, with median age of 48.8 years (range 30-75 years). Karnofsky performance status (KPS) was 60-70% for four patients and 80-100% for eight patients. Based on the Radiation Therapy Oncology Group recursive partition analysis, there were three class III patients, six class IV, one class V, and two class VI. Eleven patients underwent partial surgical tumor resection and one patient had a near complete resection. Two weeks post surgery, the patients were started on high dose TAM (120mg/m2 P.O. BID for three months). Two weeks from date of starting TAM, external beam radiotherapy (RT) was given at a dose of 59.4 Gy/33 qd fractions/6.5 weeks. Patients were assessed weekly for toxicity during treatment. Imaging studies were done at the end of two weeks of TAM, then monthly.Results:Median follow-up was 40 weeks (range 22-84 weeks). In one patient, TAM was associated with significant vomiting, necessitating the TAM dose to be decreased at three weeks and then stopped at two months. One other patient had bilateral deep venous thrombosis after 51/2 weeks on TAM, although the relationship to TAM was not firmly established. There were no radiological responses after two weeks of TAM or at the end of RT. The median time to progression was 17.7 weeks (range 5.1- 43.8 weeks). Median survival time was 33.4 weeks (range 10-79.7). Actuarial survival at 48 and 74 weeks was 40% and 15%, respectively.Conclusion:Our study shows that adjuvant high dose TAM is feasible and relatively well-tolerated. Furthermore, the combined use of high dose TAM and RT postoperatively was not associated with any significant increase in radiation-induced neurological toxicity. However, high dose TAM does not appear to improve treatment results.

Phase III Study Comparing Three Cycles of Infusional Carmustine and Cisplatin Followed by Radiation Therapy With Radiation Therapy and Concurrent Carmustine in Patients With Newly Diagnosed Supratentorial Glioblastoma Multiforme: Eastern Cooperative Oncology Group Trial 2394

2003 ◽  
Vol 21 (8) ◽  
pp. 1485-1491 ◽  
Author(s):  
Stuart A. Grossman ◽  
Anne O’Neill ◽  
Margaret Grunnet ◽  
Minesh Mehta ◽  
James L. Pearlman ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Glioblastoma Multiforme ◽  
Median Survival ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Rank Test ◽  
Newly Diagnosed ◽  
Oncology Group ◽  
Ambulatory Treatment

Purpose: This phase III Eastern Cooperative Oncology Group-Southwest Oncology Group intergroup study was conducted to determine whether three 72-hour infusions of carmustine (BiCNU) and cisplatin administered monthly before external-beam radiotherapy would improve the survival of patients with newly diagnosed glioblastoma multiforme. The control arm consisted of radiation with standard adjuvant BiCNU. Patients and Methods: A total of 223 patients were accrued from 1996 to 1999. Of these, 219 patients were eligible; 109 were randomly assigned to the experimental arm, and 110 were randomly assigned to the control arm. Randomization was stratified by age, performance status, and extent of resection. Results: The median age of the patients was 55 years; 55% were male, 93% were white, 26% had a biopsy only, and 84% were ambulatory. Treatment arms were well balanced with respect to baseline characteristics. Median follow-up time of the 15 patients still alive at the time of analysis was 3.3 years (range, 2 to 5 years). Median survival times for the standard and experimental arms were 11.2 and 11.0 months (P = .33, two-sided log-rank test), and survival at 1 year was 45% versus 44%, respectively. Fifty-six percent of patients received all three cycles of BiCNU/cisplatin, 12% received two cycles, and 31% received only one cycle. Toxicity was primarily hematologic and was more common in the experimental arm (P < .01). Conclusion: This study demonstrates that 72-hour infusions of BiCNU and cisplatin followed by radiation do not improve median survival, survival at 1 year, or time to progression. Furthermore, this treatment requires more time in the hospital and is associated with more serious toxicities than standard therapy.

Interstitial Irradiation and Hyperthermia for the Treatment of Recurrent Malignant Brain Tumors

Neurosurgery ◽  
1991 ◽  
Vol 28 (2) ◽  
pp. 206-215 ◽  
Author(s):  
Penny K. Sneed ◽  
Paul R. Stauffer ◽  
Philip H. Gutin ◽  
Theodore L. Phillips ◽  
Stuart Suen ◽  
...  
Keyword(s):  
Median Survival ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Malignant Gliomas ◽  
Helical Coil ◽  
Hyperthermia Treatment ◽  
Microwave Antennas ◽  
Interstitial Irradiation ◽  
Computed Tomographic ◽  
Melanoma Metastases

Abstract Between June 1987 and June 1989, 29 recurrent malignant gliomas or recurrent solitary brain metastases in 28 patients were treated in a Phase I study of interstitial irradiation and hyperthermia. Patient age ranged from 18 to 65 years, and the Karnofsky Performance Status scores ranged from 40 to 90%. There were 13 glioblastomas, 10 anaplastic astrocytomas. 3 melanomas, and 3 adenocarcinomas. Catheters were implanted stereotactically after computed tomography-based preplanning. Hyperthermia was administered before and after brachytherapy, using one to six 2450- or 915-MHz helical coil microwave antennas and one to three multisensor fiberoptic thermometry probes. The goal was to heat as much of the tumor as possible to 42.5±C for 30 minutes. Within 30 minutes after the first hyperthermia treatment, implant catheters were afterloaded with high-activity iodine-125 seeds delivering tumor doses of 32.6 to 61.0 Gy. Most patients had no sensation of heating. Complications included seizures in 5 patients, reversible neurological changes in 9 patients, a scalp burn in 1, and infections in 3. Of 28 evaluable 2-month follow-up scans, 11 showed definite improvement in the radiological appearance of the tumor, 4 were slightly improved, 7 were stable, and 6 showed tumor progression. Ten patients underwent reoperation for persistent tumor and/or necrosis. Eleven of 28 patients are alive 40 to 97 weeks after treatment. Thirteen patients died of a brain tumor, 2 died of extracranial melanoma metastases, 1 died of new brain melanoma metastases, and 1 died of a pulmonary embolus. The median survival was 55 weeks overall. Median survival has not yet been reached for the anaplastic astrocytoma subgroup. We conclude that interstitial brain hyperthermia using helical coil microwave antennas is technically feasible. The level of toxicity is acceptable, and the computed tomographic response rate is encouraging.

scholarly journals Clinical Efficacy of HiPorfin Photodynamic Therapy for Advanced Obstructive Esophageal Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303382093033
Author(s):  
Ruifang Zeng ◽  
Chen Liu ◽  
Libo Li ◽  
Xiaojun Cai ◽  
Run Chen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Esophageal Cancer ◽  
Radiation Therapy ◽  
Photodynamic Therapy ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Advanced Esophageal Cancer ◽  
Karnofsky Performance Status Score ◽  
Status Score ◽  
Performance Status Score

Objective: To explore the clinical efficacy of HiPorfin photodynamic therapy for advanced esophageal cancer and evaluate its impact on survival. Methods: Retrospective analysis of 32 patients with advanced obstructive esophageal cancer at our institution from September 2013 to December 2016. HiPorfin was infused as the photosensitizer at a dose of 5 mg/kg, and after 48 hours, 630-nm laser irradiation was subsequently performed through an optical fiber that passed through the biopsy channel of a flexible endoscope. Results: The effectiveness rate was 78.1% (25/32), and the significant efficacy rate was 56.3% (18/32). The dysphagia score decreased from 3.43 ± 0.73 to 1.79 ± 0.53 ( P < .05). There was no grade 3 or more toxicity. The median overall survival was estimated to be 16 months. Univariate analysis showed higher overall survival with a Karnofsky Performance Status score ≥80 compared with a Karnofsky Performance Status score <80 (hazard ratio: 2.626; 95% CI: 1.091-6.322; P = .024). Overall survival was higher in patients who had received radiation therapy than in patients who did not receive radiation therapy (hazard ratio: 3.574; 95% CI: 1.501-8.510; P = .002). Conclusion: Photodynamic therapy is an effective method for advanced esophageal cancer. The side effects are mild, and the short-term effect is good, especially in the relief of dysphagia. Photodynamic therapy can prolong the survival of patients with advanced esophageal cancer, and the Karnofsky Performance Status score and previous radiation therapy have a significant effect on the overall survival.

scholarly journals Scale to Predict Survival After Surgery for Recurrent Glioblastoma Multiforme

2010 ◽  
Vol 28 (24) ◽  
pp. 3838-3843 ◽  
Author(s):  
John K. Park ◽  
Tiffany Hodges ◽  
Leopold Arko ◽  
Michael Shen ◽  
Donna Dello Iacono ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Surgical Resection ◽  
Median Survival ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Recurrent Glioblastoma ◽  
Postoperative Survival ◽  
Recurrent Glioblastoma Multiforme ◽  
Factors Associated ◽  
Recurrent Gbm

Purpose Despite initial treatment with surgical resection, radiotherapy, and chemotherapy, glioblastoma multiforme (GBM) virtually always recurs. Surgery is sometimes recommended to treat recurrence. In this study, we sought to devise a preoperative scale that predicts survival after surgery for recurrent glioblastoma multiforme. Patients and Methods The preoperative clinical and radiographic data of 34 patients who underwent re-operation of recurrent GBM tumors were analyzed using Kaplan-Meier survival analysis and Cox proportional hazards regression modeling. The factors associated with decreased postoperative survival (P < .05) were used to devise a prognostic scale which was validated with a separate cohort of 109 patients. Results The factors associated with poor postoperative survival were: tumor involvement of prespecified eloquent/critical brain regions (P = .021), Karnofsky performance status (KPS) ≤ 80 (P = .030), and tumor volume ≥ 50 cm3 (P = .048). An additive scale (range, 0 to 3 points) comprised of these three variables distinguishes patients with good (0 points), intermediate (1 to 2 points), and poor (3 points) postoperative survival (median survival, 10.8, 4.5, and 1.0 months, respectively; P < .001). The scale identified three statistically distinct groups within the validation cohort as well (median survival, 9.2, 6.3, and 1.9 months, respectively; P < .001). Conclusion We devised and validated a preoperative scale that identifies patients likely to have poor, intermediate, and good relative outcomes after surgical resection of a recurrent GBM tumor. Application of this simple scale may be useful in counseling patients regarding their treatment options and in designing clinical trials.

scholarly journals Trans sodium crocetinate with temozolomide and radiation therapy for glioblastoma multiforme

2017 ◽  
Vol 126 (2) ◽  
pp. 460-466 ◽  
Author(s):  
John L. Gainer ◽  
Jason P. Sheehan ◽  
James M. Larner ◽  
David R. Jones
Keyword(s):  
Quality Of Life ◽  
Clinical Trial ◽  
Radiation Therapy ◽  
Glioblastoma Multiforme ◽  
Phase I ◽  
Phase Ii ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Serious Adverse Events

OBJECTIVE A new drug, trans sodium crocetinate (TSC), has been developed to enhance the delivery of oxygen to hypoxic tissues. Cancerous tumors, such as glioblastoma multiforme (GBM), are very hypoxic, and it has been suggested that radiation therapy (RT) is more beneficial if tumors are better oxygenated. A Phase I/II clinical trial was conducted to determine the effect of adding TSC to RT sessions. METHODS An open, single-arm clinical trial incorporating the standard of care (SOC) for GBM was conducted at 18 clinical sites. There were 6 weeks of RT consisting of 2 Gy/day for 5 days/week, beginning after an initial resection or stereotactic biopsy to confirm GBM. Temozolomide (TMZ), 75 mg/m2, was given before each RT session. The TSC, 0.25 mg/kg, was intravenously administered around 45 minutes before an RT session 3 days/week, usually on Monday, Wednesday, and Friday. A Phase I run-in period included 2 cohorts. The first cohort contained 3 patients who were given a half dose of the intravenous TSC (that is, 0.25 mg/kg, 3 times per week for only the first 3 weeks of RT). After a Safety Monitoring Committee (SMC) had verified that no dose-limiting toxicity (DLT) had occurred, a second cohort of 6 patients was given the same dosage of TSC but for the full 6 weeks of RT. After the SMC verified that no DLTs had occurred, Phase II began, with the administration of the full 18 doses of TSC. Fifty additional patients were enrolled during Phase II. Following the completion of RT, the patients rested for a month. After that, SOC TMZ chemotherapy (150–200 mg/m2) was administered for 5 days of the 1st week of 6 monthly cycles. No TSC was administered during this chemotherapy phase or later in the trial. Any other follow-up therapies were administered at the discretion of the individual investigators. RESULTS Kaplan-Meier analysis showed that 36% of the full-dose TSC patients were alive at 2 years, compared with historical survival values ranging from 27% to 30% for the SOC. Survival for the biopsy-only subset of patients was 40%, as compared with 42.9% for those patients having a complete resection before treatment. In addition, 2 of the 3 Phase I, Cohort 1 patients survived at 2 years. Contrast MRI data suggested that considerable pseudoprogression had occurred. Both Karnofsky Performance Status (KPS) scores and quality of life (QOL) questionnaires indicated that a good quality of life existed for most patients throughout the trial. No serious adverse events occurring in the trial were attributed to TSC. CONCLUSIONS This trial contained a single arm consisting of 59 patients. The results strongly suggested that adding TSC during RT is beneficial for the treatment of GBM. Trans sodium crocetinate offers a novel, easily implemented way to combat hypoxia in tumor tissue. Clinical trial registration no.: NCT01465347 (clinicaltrials.gov)

A Phase III comparison of BCNU, hydroxyurea, and radiation therapy to BCNU and radiation therapy for treatment of primary malignant gliomas

1979 ◽  
Vol 51 (4) ◽  
pp. 526-532 ◽  
Author(s):  
Victor A. Levin ◽  
Charles B. Wilson ◽  
Richard Davis ◽  
William M. Wara ◽  
Tana L. Pischer ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Tumor Progression ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Malignant Gliomas ◽  
Tumor Resection ◽  
Phase Iii ◽  
Tumor Type ◽  
Content Type ◽  
Fine Print

✓ This Phase III clinical trial compared the effectiveness of the combination of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), radiation therapy, and hydroxyurea (BHR group) to the combination of BCNU and radiation therapy (BR group) for the treatment of malignant gliomas. In both arms of the study, BCNU was administered intravenously for 3 consecutive days before the initiation of radiation therapy, and at 8-week intervals thereafter until unequivocal tumor progression. In the BHR arm of the study, hydroxyurea was administered orally on alternate days during radiation therapy. Patients in each arm were stratified almost equally by tumor type (glioblastoma multiforme (GM) or other nonglioblastoma multiforme malignant gliomas (NGM)) and extent of surgical resection of tumor. Patients were also evaluated with the Karnofsky Performance Status (KPS) scale. Time to progression was determined by comparing the results of sequential neurological examinations and radionuclide and computerized tomographic scans. Of the 130 patients entered into the study, 99 constitute the valid study group. Data were analyzed with Kaplan-Meier representations and the statistical methods of Gehan and Cox. The NGM patients with KPS ratings of ≥60 did better on both arms of the study, with median times to tumor progression (MTP's) of 50 and 72 weeks for BHR and BR, respectively. However, GM patients showed statistically significant differences (p = 0.03) between the two arms of the study, with MTP's of 41 and 31 weeks for BHR and BR, respectively. The GM patients with subtotal tumor resection did slightly better on BHR than on BR, with MTP's of 49 weeks (p = 0.03) and 31 weeks for the respective groups.

Survival of Patients With Newly Diagnosed Glioblastoma Multiforme Treated With RSR13 and Radiotherapy: Results of a Phase II New Approaches to Brain Tumor Therapy CNS Consortium Safety and Efficacy Study

2002 ◽  
Vol 20 (14) ◽  
pp. 3149-3155 ◽  
Author(s):  
L. Kleinberg ◽  
S.A. Grossman ◽  
K. Carson ◽  
G. Lesser ◽  
A. O’Neill ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Binding Affinity ◽  
Median Survival ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Tumor Therapy ◽  
Oxygen Binding ◽  
Newly Diagnosed

PURPOSE: The objectives of this phase II study were to determine survival, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of 2,4-[[(3,5-dimethylanilino)carbonyl]methyl]phenoxy]-2-methylpropionic acid (RSR13, efaproxiral) 100 mg/kg per day administered with standard cranial radiotherapy (RT) for the treatment of glioblastoma multiforme (GBM). RSR13, a synthetic allosteric modifier of hemoglobin, is a radiation-enhancing agent that noncovalently binds to hemoglobin, reduces oxygen-binding affinity, and increases oxygen unloading to hypoxic tissue. PATIENTS AND METHODS: Fifty patients with newly diagnosed GBM (Karnofsky performance status ≥ 60) were enrolled onto this multicenter phase II study. Patients received daily RSR13 100 mg/kg intravenously infused for 30 minutes immediately before cranial RT (60 Gy in 30 fractions). Supplemental oxygen was given during RSR13 infusion and continued until after the RT treatment was completed. RT was given within 30 minutes of the end of RSR13 infusion. PK and PD determinations were performed. RESULTS: The median survival for the RSR13-treated patients was 12.3 months with 1-year and 18-month survival rates of 54% and 24%, respectively. Twenty-four percent of patients had greater than grade 2 toxicity, which was generally transient and self-limited. A significant PD effect on hemoglobin-oxygen binding affinity was demonstrated for most patients. CONCLUSION: RSR13 (100 mg/kg) administered immediately before cranial RT is well tolerated and is pharmacodynamically active. Median survival in excess of 1 year is favorable.

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