A Phase I Dose-Escalation Study (ISIDE-BT-1) of Accelerated IMRT With Temozolomide in Patients With Glioblastoma

Journal Article · Sat May 01 04:00:00 EDT 2010 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2009.04.064· OSTI ID:21372245

Morganti, Alessio G ^[1]; Balducci, Mario ^[2]; Salvati, Maurizio; Esposito, Vincenzo; Romanelli, Pantaleo ^[3]; Ferro, Marica ^[1]; Calista, Franco ^[4]; Digesu, Cinzia ^[1]; Macchia, Gabriella ^[1]; Ianiri, Massimo ^[5]; Deodato, Francesco ^[1]; Cilla, Savino; Piermattei, Angelo M.P. ^[6]; Valentini, Vincenzo; Cellini, Numa ^[2]; Cantore, Gian Paolo ^[3]

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1. Department of Radiotherapy, John Paul II Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso (Italy)
2. Department of Radiotherapy, Policlinico Universitario A. Gemelli, Catholic University, Rome (Italy)
3. Department of Neurosurgery, Neuromed Institute, Pozzilli (Italy)
4. Department of Palliative Therapies, John Paul II Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso (Italy)
5. Department of Neurosurgery, A. Cardarelli Hospital, Campobasso (Italy)
6. Department of Medical Physics, John Paul II Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso (Italy)

Purpose: To determine the maximum tolerated dose (MTD) of fractionated intensity-modulated radiotherapy (IMRT) with temozolomide (TMZ) in patients with glioblastoma. Methods and Materials: A Phase I clinical trial was performed. Eligible patients had surgically resected or biopsy-proven glioblastoma. Patients started TMZ (75 mg/day) during IMRT and continued for 1 year (150-200 mg/day, Days 1-5 every 28 days) or until disease progression. Clinical target volume 1 (CTV1) was the tumor bed +- enhancing lesion with a 10-mm margin; CTV2 was the area of perifocal edema with a 20-mm margin. Planning target volume 1 (PTV1) and PTV2 were defined as the corresponding CTV plus a 5-mm margin. IMRT was delivered in 25 fractions over 5 weeks. Only the dose for PTV1 was escalated (planned dose escalation: 60 Gy, 62.5 Gy, 65 Gy) while maintaining the dose for PTV2 (45 Gy, 1.8 Gy/fraction). Dose limiting toxicities (DLT) were defined as any treatment-related nonhematological adverse effects rated as Grade >=3 or any hematological toxicity rated as >=4 by Radiation Therapy Oncology Group (RTOG) criteria. Results: Nineteen consecutive glioblastoma were treated with step-and-shoot IMRT, planned with the inverse approach (dose to the PTV1: 7 patients, 60 Gy; 6 patients, 62.5 Gy; 6 patients, 65 Gy). Five coplanar beams were used to cover at least 95% of the target volume with the 95% isodose line. Median follow-up time was 23 months (range, 8-40 months). No patient experienced DLT. Grade 1-2 treatment-related neurologic and skin toxicity were common (11 and 19 patients, respectively). No Grade >2 late neurologic toxicities were noted. Conclusion: Accelerated IMRT to a dose of 65 Gy in 25 fractions is well tolerated with TMZ at a daily dose of 75 mg.

• OSTI ID: 21372245
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 1 Vol. 77; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
DISEASES
DOSES
FRACTIONATED IRRADIATION
GLIOMAS
IRRADIATION
MEDICINE
NEOPLASMS
NERVOUS SYSTEM DISEASES
NUCLEAR MEDICINE
RADIATION DOSES
RADIOLOGY
RADIOTHERAPY
THERAPY
TOXICITY