Synapse - Phase I study of samarium-153 lexidronam with docetaxel in castration-resistant metastatic prostate cancer

Phase I study of samarium-153 lexidronam with docetaxel in castration-resistant metastatic prostate cancer Journal Article

Authors:	Morris, M. J.; Pandit-Taskar, N.; Carrasquillo, J.; Divgi, C. R.; Slovin, S.; Kelly, W. K.; Rathkopf, D.; Gignac, G. A.; Solit, D.; Schwartz, L.; Stephenson, R. D.; Hong, C.; Delacruz, A.; Curley, T.; Heller, G.; Jia, X.; O'Donoghue, J.; Larson, S.; Scher, H. I.
Article Title:	Phase I study of samarium-153 lexidronam with docetaxel in castration-resistant metastatic prostate cancer
Abstract:	Purpose Early studies of patients with castration-resistant metastatic prostate cancer (CRMPC) suggest that chemotherapy administered with a dose of a bone-seeking radiopharmaceutical is superior to chemotherapy alone. To build on this strategy and fully integrate a repetitively dosed bone-seeking radiopharmaceutical into a contemporary chemotherapy regimen, we conducted a phase I study of docetaxel and samarium-153 (Sm-153) lexidronam. Patients and Methods Men with progressive CRMPC were eligible. Cohorts of three to six patients were defined by dose escalations as follows: docetaxel 65, 70, 75, 75, 75 mg/m(2) and Sm-153 ethylenediaminetetramethylenephosphonate (EDTMP) 0.5, 0.5, 0.5, 0.75, 1 mCi/kg. Each cycle lasted a minimum of 6 (cohorts 1 through 5) or 9 ( cohort 6) weeks. Docetaxel was administered on days 1 and 22 ( and day 43 for cohort 6), and Sm-153-EDTMP was administered on day -1 to 1 of each cycle. Patients with acceptable hematologic toxicities were eligible to receive additional cycles until progression. Results Twenty-eight men were treated in six cohorts. Maximum-tolerated dose was not reached, because full doses of both agents were well tolerated, even using an every-6-week dosing schedule of Sm-153-EDTMP. Patients received an average of 5.6 docetaxel doses ( range, one to 13 doses) and 2.9 Sm-153-EDTMP doses ( range, one to six doses). Fifteen patients demonstrated a more than 50% decline in prostate-specific antigen. Treatment significantly reduced indices of bone deposition and resorption. Conclusion Docetaxel and Sm-153-EDTMP can be combined safely at full doses over repeated cycles. Responses were seen in the small group of patients with taxane-resistant disease tested. The optimal phase II doses for patients with taxane-naive disease may differ from those optimal for patients with taxane-resistant disease.
Keywords:	prednisone; mitoxantrone; carcinoma; bone; safety; men; markers
Journal Title:	Journal of Clinical Oncology
Volume:	27
Issue:	15
ISSN:	0732-183X
Publisher:	American Society of Clinical Oncology
Date Published:	2009-05-01
Start Page:	2436
End Page:	2442
Language:	English
ACCESSION:	ISI:000266195400007
DOI:	10.1200/jco.2008.20.4164
PROVIDER:	wos
PMCID:	PMC2684850
PUBMED:	19364960
Notes:	--- - Article - "Source: Wos"