scholarly journals Phase II Study of Erlotinib Plus Temozolomide During and After Radiation Therapy in Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma

2009 ◽  
Vol 27 (4) ◽  
pp. 579-584 ◽  
Author(s):  
Michael D. Prados ◽  
Susan M. Chang ◽  
Nicholas Butowski ◽  
Rebecca DeBoer ◽  
Rupa Parvataneni ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Molecular Markers ◽  
Glioblastoma Multiforme ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Methylation Status ◽  
Strong Positive Correlation ◽  
Newly Diagnosed ◽  
Phase Ii Trials ◽  
Open Label

Purpose This open-label, prospective, single-arm, phase II study combined erlotinib with radiation therapy (XRT) and temozolomide to treat glioblastoma multiforme (GBM) and gliosarcoma. The objectives were to determine efficacy of this treatment as measured by survival and to explore the relationship between molecular markers and treatment response. Patients and Methods Sixty-five eligible adults with newly diagnosed GBM or gliosarcoma were enrolled. We intended to treat patients not currently treated with enzyme-inducing antiepileptic drugs (EIAEDs) with 100 mg/d of erlotinib during XRT and 150 mg/d after XRT. Patients receiving EIAEDs were to receive 200 mg/d of erlotinib during XRT and 300 mg/d after XRT. After XRT, the erlotinib dose was escalated until patients developed tolerable grade 2 rash or until the maximum allowed dose was reached. All patients received temozolomide during and after XRT. Molecular markers of epidermal growth factor receptor (EGFR), EGFRvIII, phosphatase and tensin homolog (PTEN), and methylation status of the promotor region of the MGMT gene were analyzed from tumor tissue. Survival was compared with outcomes from two historical phase II trials. Results Median survival was 19.3 months in the current study and 14.1 months in the combined historical control studies, with a hazard ratio for survival (treated/control) of 0.64 (95% CI, 0.45 to 0.91). Treatment was well tolerated. There was a strong positive correlation between MGMT promotor methylation and survival, as well as an association between MGMT promotor-methylated tumors and PTEN positivity shown by immunohistochemistry with improved survival. Conclusion Patients treated with the combination of erlotinib and temozolomide during and following radiotherapy had better survival than historical controls. Additional studies are warranted.

Promising Survival for Patients With Newly Diagnosed Glioblastoma Multiforme Treated With Concomitant Radiation Plus Temozolomide Followed by Adjuvant Temozolomide

2002 ◽  
Vol 20 (5) ◽  
pp. 1375-1382 ◽  
Author(s):  
Roger Stupp ◽  
Pierre-Yves Dietrich ◽  
Sandrine Ostermann Kraljevic ◽  
Alessia Pica ◽  
Ivan Maillard ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Phase Ii ◽  
Pneumocystis Carinii ◽  
Survival Rates ◽  
Concomitant Treatment ◽  
Newly Diagnosed ◽  
Open Label ◽  
Fractionated Radiotherapy ◽  
Adjuvant Temozolomide ◽  
Grade 3

PURPOSE: Temozolomide is a novel oral alkylating agent with demonstrated efficacy as second-line therapy for patients with recurrent anaplastic astrocytoma and glioblastoma multiforme (GBM). This phase II study was performed to determine the safety, tolerability, and efficacy of concomitant radiation plus temozolomide therapy followed by adjuvant temozolomide therapy in patients with newly diagnosed GBM. PATIENTS AND METHODS: Sixty-four patients were enrolled onto this open-label, phase II trial. Temozolomide (75 mg/m2/d × 7 d/wk for 6 weeks) was administered orally concomitant with fractionated radiotherapy (60 Gy total dose: 2 Gy × 5 d/wk for 6 weeks) followed by temozolomide monotherapy (200 mg/m2/d × 5 days, every 28 days for six cycles). The primary end points were safety and tolerability, and the secondary end point was overall survival. RESULTS: Concomitant radiation plus temozolomide therapy was safe and well tolerated. Nonhematologic toxicities were rare and mild to moderate in severity. During the concomitant treatment phase, grade 3 or 4 neutropenia, thrombocytopenia, or both were observed in 6% of patients, including two severe infections with Pneumocystis carinii. During adjuvant temozolomide, 2% and 6% of cycles were associated with grade 3 and 4 neutropenia or thrombocytopenia, respectively. Median survival was 16 months, and the 1- and 2-year survival rates were 58% and 31%, respectively. Patients younger than 50 years old and patients who underwent debulking surgery had the best survival outcome. CONCLUSION: Continuous daily temozolomide and concomitant radiation is safe. This regimen of concomitant chemoradiotherapy followed by adjuvant chemotherapy may prolong the survival of patients with glioblastoma. Further investigation is warranted, and a randomized trial is ongoing.

scholarly journals Phase II study of hypofractionated radiation therapy in elderly patients with newly diagnosed glioblastoma with poor prognosis

2018 ◽  
Vol 105 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Pierina Navarria ◽  
Federico Pessina ◽  
Luca Cozzi ◽  
Stefano Tomatis ◽  
Giacomo Reggiori ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Observation Time ◽  
Primary Objective ◽  
Karnofsky Performance Scale ◽  
Newly Diagnosed ◽  
Newly Diagnosed Glioblastoma ◽  
Hypofractionated Radiation Therapy ◽  
Hypofractionated Radiation

Objective: To evaluate hypofractionated radiation therapy (HFRT) given at therapeutic effective doses in a phase II study. Endpoints were progression-free survival (PFS) rate, overall survival (OS), and incidence of toxicity. Methods: Patients with newly diagnosed glioblastoma, age ⩾70 years, Karnofsky performance scale (KPS) score ⩽60, were enrolled. The total dose of HFRT was 52.5 Gy/15 fractions, corresponded to a biological effective dose to the tumor of 70.88 Gy. Results: Thirty patients were treated, with a median age of 75 years. Concurrent and adjuvant temozolomide chemotherapy (TMZ-CHT) was administered in 7 (23.3%) and 11 (40.7%) patients received only adjuvant TMZ-CHT. The median, 6-month PFS, and 12-month PFS were 5.0 months, 43.3%, and 20%, respectively. The median, 6-month OS, and 12-month OS were 8 months, 90%, and 30%, respectively. At the last observation time, 26 patients (86.7%) were dead and 4 (13.3%) were alive. No increase in steroid drugs was required during radiotherapy treatment and a reduction was possible in 12 (40%). Patients with KPS=60, RPA V, MGMT methylated status, neurological status stable or improved after surgery and who underwent HFRT with concurrent and adjuvant CHT, had the better outcome. Conclusion: HFRT has proven to be feasible and effective, with limited morbidity, for selected elderly and frail patients with newly diagnosed glioblastoma. The primary objective of this study was not reached in the whole cohort but only in selected patients, who need more aggressive treatment.

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