Phase II Pilot Study of Bevacizumab in Combination with Temozolomide and Regional Radiation Therapy for Up-Front Treatment of Patients With Newly Diagnosed Glioblastoma Multiforme: Interim Analysis of Safety and Tolerability

• Published in: International journal of radiation oncology, biology, physics Vol. 71; no. 5; pp. 1372 - 1380
• Main Authors: Lai, Albert, M.D., Ph.D, Filka, Emese, McGibbon, Bruce, M.D, Nghiemphu, Phioanh Leia, M.D, Graham, Carrie, Yong, William H., M.D, Mischel, Paul, M.D, Liau, Linda M., M.D., Ph.D, Bergsneider, Marvin, M.D, Pope, Whitney, M.D., Ph.D, Selch, Michael, M.D, Cloughesy, Tim, M.D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2008
• Subjects: Adult; Aged; Angiogenesis Inhibitors - adverse effects; Antiangiogenesis; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Alkylating - adverse effects; Bevacizumab; Brain Neoplasms - drug therapy; Brain Neoplasms - radiotherapy; Combined Modality Therapy - adverse effects; Combined Modality Therapy - methods; Dacarbazine - administration & dosage; Dacarbazine - adverse effects; Dacarbazine - analogs & derivatives; Drug Administration Schedule; Drug Therapy, Combination; FATIGUE; Female; Glioblastoma - drug therapy; Glioblastoma - radiotherapy; GLIOMAS; Hematology, Oncology and Palliative Medicine; Humans; Male; Middle Aged; Newly diagnosed glioblastoma; PATIENTS; Pilot Projects; Radiation; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; SURGERY; Temozolomide; THROMBOSIS; TOXICITY; WOUNDS; Newly diagnosed glioblastoma; Temozolomide; Antiangiogenesis; Radiation; Bevacizumab
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2007.11.068

Purpose To assess interim safety and tolerability of a 10-patient, Phase II pilot study using bevacizumab (BV) in combination with temozolomide (TMZ) and regional radiation therapy (RT) in the up-front treatment of patients with newly diagnosed glioblastoma. Methods and Materials All patients received standard external beam regional RT of 60.0 Gy in 30 fractions started within 3 to 5 weeks after surgery. Concurrently TMZ was given daily at 75 mg/m2 for 42 days during RT, and BV was given every 2 weeks at 10 mg/kg starting with the first day of RT/TMZ. After a 2-week interval upon completion of RT, the post-RT phase commenced with resumption of TMZ at 150 to 200 mg/m2 for 5 days every 4 weeks and continuation of BV every 2 weeks. Results For these 10 patients, toxicities were compiled until study discontinuation or up to ∼40 weeks from initial study treatment for those remaining on-study. In terms of serious immediate or delayed neurotoxicity, 1 patient developed presumed radiation-induced optic neuropathy. Among the toxicities that could be potentially treatment related, relatively high incidences of fatigue, myelotoxicity, wound breakdown, and deep venous thrombosis/pulmonary embolism were observed. Conclusion The observed toxicities were acceptable to continue enrollment toward the overall target group of 70 patients. Preliminary efficacy analysis shows encouraging mean progression-free survival. At this time data are not sufficient to encourage routine off-label use of BV combined with TMZ/RT in the setting of newly diagnosed glioblastoma without longer follow-up, enrollment of additional patients, and thorough efficacy assessment.