1. Phase I study of samarium-153 lexidronam with docetaxel in castration-resistant metastatic prostate cancer.
- Author
-
Morris MJ, Pandit-Taskar N, Carrasquillo J, Divgi CR, Slovin S, Kelly WK, Rathkopf D, Gignac GA, Solit D, Schwartz L, Stephenson RD, Hong C, Delacruz A, Curley T, Heller G, Jia X, O'Donoghue J, Larson S, and Scher HI
- Subjects
- Adenocarcinoma secondary, Adult, Aged, Aged, 80 and over, Analgesics, Non-Narcotic administration & dosage, Analgesics, Non-Narcotic adverse effects, Bone Neoplasms drug therapy, Bone Neoplasms secondary, Bone and Bones drug effects, Docetaxel, Drug Resistance, Neoplasm, Humans, Male, Maximum Tolerated Dose, Middle Aged, Organometallic Compounds administration & dosage, Organometallic Compounds adverse effects, Organophosphorus Compounds administration & dosage, Organophosphorus Compounds adverse effects, Prostate-Specific Antigen blood, Prostate-Specific Antigen drug effects, Prostatic Neoplasms pathology, Radiopharmaceuticals administration & dosage, Radiopharmaceuticals adverse effects, Taxoids administration & dosage, Taxoids adverse effects, Adenocarcinoma drug therapy, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Prostatic Neoplasms drug therapy
- 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.
- Published
- 2009
- Full Text
- View/download PDF