TY - JOUR
T1 - Safety and feasibility of motexafin gadolinium administration with whole brain radiation therapy and stereotactic radiosurgery boost in the treatment of ≤6 brain metastases
T2 - A multi-institutional phase II trial
AU - McHaffie, Derek R.
AU - Chabot, Pierre
AU - Dagnault, Anne
AU - Suh, John H.
AU - Fortin, Marie Andrée
AU - Chang, Eric
AU - Timmerman, Robert
AU - Souhami, Luis
AU - Grecula, John
AU - Nabid, Abdenour
AU - Schultz, Chris
AU - Werner-Wasik, Maria
AU - Gaspar, Laurie E.
AU - Brachman, David
AU - Mody, Tarak
AU - Mehta, Minesh P.
N1 - Funding Information:
Acknowledgments Trial was sponsored and supported by Phar-macyclics Inc., Sunnyvale, CA.
PY - 2011/11
Y1 - 2011/11
N2 - To determine the safety, tolerability, and report on secondary efficacy endpoints of motexafin gadolinium (MGd) in combination with whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) for patients with ≤6 brain metastases. We conducted an international study of WBRT (37.5 Gy in 15 fractions) and SRS (15-21 Gy) with the addition of MGd (5 mg/kg preceding each fraction beginning week 2). The primary endpoint was to evaluate the rate of irreversible grade 3 or any grade ≥4 neurotoxicity and establish feasibility in preparation for a phase III trial. Sixty-five patients were enrolled from 14 institutions, of which 45 (69%) received SRS with MGd as intended and were available for evaluation. Grade ≥3 neurotoxicity attributable to radiation therapy within 3 months of SRS was seen in 2 patients (4.4%), including generalized weakness and radionecrosis requiring surgical management. Immediately following the course of MGd plus WBRT, new brain metastases were detected in 11 patients (24.4%) at the time of the SRS treatment planning MRI. The actuarial incidence of neurologic progression at 6 months and 1 year was 17 and 20%, respectively. The median investigator-determined neurologic progression free survival and overall survival times were 8 (95% CI: 5-14) and 9 months (95% CI: 6-not reached), respectively. We observed a low rate of neurotoxicity, demonstrating that the addition of MGd does not increase the incidence or severity of neurologic complications from WBRT with SRS boost.
AB - To determine the safety, tolerability, and report on secondary efficacy endpoints of motexafin gadolinium (MGd) in combination with whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) for patients with ≤6 brain metastases. We conducted an international study of WBRT (37.5 Gy in 15 fractions) and SRS (15-21 Gy) with the addition of MGd (5 mg/kg preceding each fraction beginning week 2). The primary endpoint was to evaluate the rate of irreversible grade 3 or any grade ≥4 neurotoxicity and establish feasibility in preparation for a phase III trial. Sixty-five patients were enrolled from 14 institutions, of which 45 (69%) received SRS with MGd as intended and were available for evaluation. Grade ≥3 neurotoxicity attributable to radiation therapy within 3 months of SRS was seen in 2 patients (4.4%), including generalized weakness and radionecrosis requiring surgical management. Immediately following the course of MGd plus WBRT, new brain metastases were detected in 11 patients (24.4%) at the time of the SRS treatment planning MRI. The actuarial incidence of neurologic progression at 6 months and 1 year was 17 and 20%, respectively. The median investigator-determined neurologic progression free survival and overall survival times were 8 (95% CI: 5-14) and 9 months (95% CI: 6-not reached), respectively. We observed a low rate of neurotoxicity, demonstrating that the addition of MGd does not increase the incidence or severity of neurologic complications from WBRT with SRS boost.
KW - Brain metastases
KW - Motexafin gadolinium
KW - Stereotactic radiosurgery
KW - Whole-brain radiotherapy
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U2 - 10.1007/s11060-011-0590-9
DO - 10.1007/s11060-011-0590-9
M3 - Article
C2 - 21523486
AN - SCOPUS:82955233755
SN - 0167-594X
VL - 105
SP - 301
EP - 308
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
IS - 2
ER -