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

Authors

• Michael J Morris
• Neeta Pandit-Taskar
• Jorge Carrasquillo
• Chaitanya R Divgi
• Susan Slovin
• William K Kelly
• Dana Rathkopf
• Gretchen A Gignac
• David Solit
• Lawrence Schwartz
• Ryan D Stephenson
• Christina Hong
• Anthony Delacruz
• Tracy Curley
• Glenn Heller
• Xiaoyu Jia
• Joseph O'Donoghue
• Steven Larson
• Howard I Scher

Publication/Presentation Date

5-20-2009

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 ((153)Sm) 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 (153)Sm 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 (153)Sm-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 (153)Sm-EDTMP. Patients received an average of 5.6 docetaxel doses (range, one to 13 doses) and 2.9 (153)Sm-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 (153)Sm-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-naïve disease may differ from those optimal for patients with taxane-resistant disease.

Volume

27

Issue

15

First Page

2436

Last Page

2442

ISSN

1527-7755

Published In/Presented At

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. (2009). Phase I study of samarium-153 lexidronam with docetaxel in castration-resistant metastatic prostate cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 27(15), 2436–2442. https://doi.org/10.1200/JCO.2008.20.4164

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

19364960

Department(s)

Administration and Leadership

Document Type

Article