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A phase I factorial design study of dose-dense temozolomide alone and in combination with thalidomide, isotretinoin, and/or celecoxib as postchemoradiation adjuvant therapy for newly diagnosed glioblastoma
- Source :
- Neuro-Oncology
- Publication Year :
- 2010
- Publisher :
- Oxford University Press, 2010.
-
Abstract
- External beam radiation therapy (XRT) with concomitant temozolomide and 6 cycles of adjuvant temozolomide (5/28-day schedule) improves survival in patients with newly diagnosed glioblastoma compared with XRT alone. Studies suggest that dose-dense temozolomide schedules and addition of cytostatic agents may further improve efficacy. This factorial design phase I/II protocol tested dose-dense temozolomide alone and combined with cytostatic agents. Patients with newly diagnosed glioblastoma received fractionated XRT to 60 Gy concomitant with temozolomide (75 mg/m²)/day for 42 days). In the phase I portion, patients with stable disease or radiologic response 1 month after chemoradiation were randomized to adjuvant temozolomide alone (150 mg/m²/day, 7/14-day schedule) or with doublet combinations of thalidomide (400 mg/day), isotretinoin (100 mg/m²/day), and/or celecoxib (400 mg twice daily), or all 3 agents. Toxicity was assessed after 4 weeks. Among 54 patients enrolled (median age, 52 years; median Karnofsky performance status, 90), adjuvant treatment was not administered to 12 (22%), primarily because of disease progression (n = 10). All combinations were well tolerated. Grade 3/4 lymphopenia developed in 63% of patients, but no related infections occurred. One patient treated with temozolomide plus isotretinoin plus thalidomide had dose-limiting grade 3 fatigue and rash, and 1 patient receiving all 4 agents had dose-limiting grade 4 neutropenia. Venous thrombosis occurred in 7 patients, 4 of whom received thalidomide. From study entry, median survival was 20 months and the 2-year survival rate was 40%. Multiple cytostatic agents can be safely combined with dose-dense temozolomide. The factorial-based phase II portion of this study is currently ongoing.
- Subjects :
- Adult
Male
Cancer Research
medicine.medical_specialty
Adolescent
medicine.medical_treatment
Clinical Investigations
Antineoplastic Agents
temozolomide
Kaplan-Meier Estimate
Neutropenia
Gastroenterology
Neurosurgical Procedures
Young Adult
Internal medicine
Glioma
glioma
medicine
Adjuvant therapy
Humans
Isotretinoin
Survival rate
radiotherapy
Aged
Chemotherapy
Sulfonamides
Temozolomide
business.industry
glioblastoma
Supratentorial Neoplasms
Middle Aged
medicine.disease
Combined Modality Therapy
Surgery
Thalidomide
Dacarbazine
Oncology
Celecoxib
Chemotherapy, Adjuvant
Concomitant
dose-dense
Pyrazoles
Female
Neurology (clinical)
business
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 15235866 and 15228517
- Volume :
- 12
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Neuro-Oncology
- Accession number :
- edsair.doi.dedup.....2a98ab6d49d4ee711f27453a04a561f8