Thema: News: Radiation therapy plus high dose tamoxifen
News: Radiation therapy plus high dose tamoxifen
Karen[a]
08.06.2004 21:59:47
A phase II trial of conventional radiation therapy (XRT) plus high dose tamoxifen (TAM) for the treatment of supratentorial glioblastoma multiforme (GBM): RTOG protocol BR-0021.
Abstract No: 1529
Author(s): H. I. Robins, M. Won, C. Schultz, A. Choucair, D. Brachman, W. Demas, M. Mehta; UWCCC, Madison, WI; RTOG, Philadelphia, PA; Medical College of Wisconsin, Milwaukee, WI; LDS Hospital, Salt Lake City, UT; Foundation for Cancer Research and Education, Phoenix, AZ; Summa Health Systems, Akron, OH
Background:
Preclinical studies support the concept that inhibition of protein kinase C (PKC) by TAM should provide both anti-neoplastic effects and radiosensitization. Methods: High dose TAM (80 mg/m2 PO daily in divided doses) was given with and after conventional XRT to inhibit PKC mediated signaling, which is known to be enhanced in GBM. Patients (n=77) were accrued between 12/00-12/01; 75 patients were analyzable. Pretreatment characteristics included: 52%<60 years of age; 39% had a Zubrod score of 0, 70% had minor or no neurological symptoms; 65% were RTOG -recursive partition analysis (RPA) class III & IV.
Results:
A sample of 46 patients was reviewed for TAM delivery; 78% achieved acceptable dosing. Notable toxicity included: Late radiation Grade (G) G3 =2; Thrombo-embolic disease G2=2, G3=8, G4=3, G5=1 for an incidence of 18.7%, (which is lower than expected, based on the literature for DVT in GBM patients not receiving TAM). Median survival time (MST) was 9.7 months (M). This result was compared (using 3 different statistical methodologies) to the historical GBM control database of 1443 drug / XRT treated patients RPA class III, IV, & V. After controlling for RPA class IV, the MST was 11.3M, which compares to the historical RPA control of 11.2 M (p=0.38). Conclusions: 1) The results obtained do not exhibit a substantial advance over previous studies with various XRT/drug doublets including BCNU. As TAM does not have significant overlapping toxicities with most other drugs, its testing in a combined modality approach with other medications may be justified in future clinical trails. 2) Historically the incidence of thrombo-embolic events in GBM patients is ~30%. The lower than expected incidence seen here has also been observed in other high dose TAM GBM studies. We speculate that TAM inhibited the PKC mediated phosphorylation of coagulation factors.
Event: 2004 ASCO Annual Meeting
Presenter: H. I. Robins, MD, PhD
Session: Central Nervous System Tumors
Abstract No: 1529
Author(s): H. I. Robins, M. Won, C. Schultz, A. Choucair, D. Brachman, W. Demas, M. Mehta; UWCCC, Madison, WI; RTOG, Philadelphia, PA; Medical College of Wisconsin, Milwaukee, WI; LDS Hospital, Salt Lake City, UT; Foundation for Cancer Research and Education, Phoenix, AZ; Summa Health Systems, Akron, OH
Background:
Preclinical studies support the concept that inhibition of protein kinase C (PKC) by TAM should provide both anti-neoplastic effects and radiosensitization. Methods: High dose TAM (80 mg/m2 PO daily in divided doses) was given with and after conventional XRT to inhibit PKC mediated signaling, which is known to be enhanced in GBM. Patients (n=77) were accrued between 12/00-12/01; 75 patients were analyzable. Pretreatment characteristics included: 52%<60 years of age; 39% had a Zubrod score of 0, 70% had minor or no neurological symptoms; 65% were RTOG -recursive partition analysis (RPA) class III & IV.
Results:
A sample of 46 patients was reviewed for TAM delivery; 78% achieved acceptable dosing. Notable toxicity included: Late radiation Grade (G) G3 =2; Thrombo-embolic disease G2=2, G3=8, G4=3, G5=1 for an incidence of 18.7%, (which is lower than expected, based on the literature for DVT in GBM patients not receiving TAM). Median survival time (MST) was 9.7 months (M). This result was compared (using 3 different statistical methodologies) to the historical GBM control database of 1443 drug / XRT treated patients RPA class III, IV, & V. After controlling for RPA class IV, the MST was 11.3M, which compares to the historical RPA control of 11.2 M (p=0.38). Conclusions: 1) The results obtained do not exhibit a substantial advance over previous studies with various XRT/drug doublets including BCNU. As TAM does not have significant overlapping toxicities with most other drugs, its testing in a combined modality approach with other medications may be justified in future clinical trails. 2) Historically the incidence of thrombo-embolic events in GBM patients is ~30%. The lower than expected incidence seen here has also been observed in other high dose TAM GBM studies. We speculate that TAM inhibited the PKC mediated phosphorylation of coagulation factors.
Event: 2004 ASCO Annual Meeting
Presenter: H. I. Robins, MD, PhD
Session: Central Nervous System Tumors
Karen[a]
