Publications [#140376] of John H Sampson

Papers Published

1. MA Vogelbaum, JH Sampson, S Kunwar, SM Chang, M Shaffrey, AL Asher, FF Lang, D Croteau, K Parker, AY Grahn, JW Sherman, SR Husain, RK Puri, CONVECTION-ENHANCED DELIVERY OF CINTREDEKIN BESUDOTOX (INTERLEUKIN-13-PE38QQR) FOLLOWED BY RADIATION THERAPY WITH AND WITHOUT TEMOZOLOMIDE IN NEWLY DIAGNOSED MALIGNANT GLIOMAS: PHASE 1 STUDY OF FINAL SAFETY RESULTS., Neurosurgery (October, 2007), ISSN 1524-4040
   (last updated on 2007/12/20)

   Abstract:
   OBJECTIVE: Cintredekin besudotox (CB), a recombinant cytotoxin consisting of interleukin-13 and truncated Pseudomonas exotoxin, binds selectively to interleukin-13Ralpha2 receptors overexpressed by malignant gliomas. This study assessed the safety of CB administered by convection-enhanced delivery followed by standard external beam radiation therapy (EBRT) with or without temozolomide (Temodar; Schering-Plough, Kenilworth, NJ) in patients with newly diagnosed malignant gliomas. METHODS: After gross total resection of the tumor, two to four intraparenchymal catheters were stereotactically placed and CB (0.25 or 0.5 mug/mL) was infused for 96 hours. This was followed, 10 to 14 days later, by EBRT (5940-6100 cGy, 5 d/wk for 6-7 wk) with or without temozolomide (75 mg/m/d, 7 d/wk during EBRT). Safety was assessed during an 11-week observation period after catheter placement RESULTS: Twenty-two patients (12 men, 10 women; median age, 55 yr; 21 with glioblastoma multiforme and one with an anaplastic mixed oligoastrocytoma) were enrolled. None of the patients experienced dose-limiting toxicities in the first two cohorts (0.25 mug/mL CB + EBRT [n = 3] and 0.25 mug/mL CB + EBRT + temozolomide [n = 3]). One patient experienced a dose-limiting toxicity (Grade 4 seizure) in the third cohort (0.5 mug/mL CB + EBRT [n = 6]). Six patients in the final cohort (0.5 mug/mL CB + EBRT + temozolomide [n = 10]) completed treatment, and one patient experienced a dose-limiting toxicity (Grade 3 aphasia and confusion). Four patients were not considered evaluable for a dose decision and were replaced. CB-related adverse events occurring in more than one patient were fatigue, gait disturbance, nystagmus, and confusion. No Grade 3 to 4 hematological toxicities were observed. CONCLUSION: CB (0.5 mug/mL) administered via convection-enhanced delivery before standard radiochemotherapy seems to be well tolerated in adults with newly diagnosed malignant gliomas. Further clinical study assessment is warranted.