Phase I trial with a combination of docetaxel and ¹⁵³Sm-lexidronam in patients with castration-resistant metastatic prostate cancer.
BACKGROUND
This study was designed to evaluate toxicity and preliminary efficacy of 2 cycles of concomitant standard dose/schedule of (153)Sm-lexidronam plus Q 3 weeks schedule escalating doses of docetaxel in metastatic castration-resistant prostate cancer (mCRPC).


METHODS
mCRPC patients with progressive bone metastases were treated in 4 cohorts. Docetaxel doses were escalated from 50, 50, 0 mg/m(2) (on days 1, 22, 43, per 12-week cycle) to 75, 75, 75 mg/m(2). (153)Sm-lexidronam was administered on days 2 (Q 12 weeks) at dose of 1 mCi/kg/cycle (maximum of 2 cycles).


RESULTS
Thirteen patients received an average of 3.6 doses of docetaxel (range, 2-6 doses, median 4) and 1.5 doses of (153)Sm-lexidronam (range, 1-2, median 2). Toxicity was primarily hematologic. There were total 35 episodes grade 3/4 neutropenia with a median 7 (range 7-14) days to recovery to ≤grade 1. One dose limiting grade 3 thrombocytopenia occurred on cohorts 3 and 4. Eight of 13 (62%) patients had PSA > 50% decrease as best response during the treatment. Median time to bone disease progression was 5.2 months (range 91 days-10 months+); 6/13 (46%) patients had stable/improved bone scans at 6 months and 6/6 (100%) symptomatic patients had improvement in pain.


CONCLUSIONS
Concurrent 6-month administration of 4 doses (75 mg/m(2)) of standard Q 3 weeks schedule of docetaxel with 2 Q 3 months infusions of 1 mCi/Kg (153)Sm-lexidronam is feasible with reversible bone marrow suppression, and deserves further testing in mCRPC patients with extensive bone metastasis.
Lin
Jianqing
J
Prostate Cancer Program, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21231, USA.
Sinibaldi
Victoria J
VJ
Carducci
Michael A
MA
Denmeade
Samuel
S
Song
Danny
D
Deweese
Theodore
T
Eisenberger
Mario A
MA
D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000556:secondary; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008875:Middle Aged; D009919:Orchiectomy; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000009:adverse effects; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000009:adverse effects; D010146:Pain / Q000188:drug therapy / Q000209:etiology; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
D018712:Analgesics, Non-Narcotic; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D011838:Radiation-Sensitizing Agents; D043823:Taxoids; D000077143:Docetaxel; C061972:samarium Sm-153 lexidronam; D017430:Prostate-Specific Antigen