Phase I study of concurrent weekly docetaxel and repeated samarium-153 lexidronam in patients with castration-resistant metastatic prostate cancer.
OBJECTIVE
Samarium-153 ((153)Sm) lexidronam is a bone-targeting radiopharmaceutical with a short physical half-life and a favorable toxicity profile. We evaluated the safety and feasibility of a concurrent combination of weekly docetaxel with repeated (153)Sm-lexidronam in patients with castration-resistant prostate cancer (CRPC).


METHODS
A conventional 3 + 3 dose-escalation design was used for this study. Patients were treated in three cohorts comprising two cycles of weekly docetaxel at 25, 30, and 35 mg/m(2), respectively, on days 1, 8, and 15 of a 28-day cycle in combination with (153)Sm (1 mCi/kg) on day 1. Unacceptable hematologic toxicity (UHT) was defined as more than 7 days delay in therapy for inadequate counts: an absolute neutrophil count (ANC) more than 1,000/microL and platelets more than 70,000/microL were required at days 8 and 15 and ANC more than 1,500/microL and platelets more than 100,000/microL were required at cycle 2, day 1. If counts had not recovered by day 56 of either combination cycle, UHT was declared.


RESULTS
Eighteen patients were treated in three cohorts. Two patients in separate cohorts experienced UHT; the maximum-tolerated dose for this regimen was not reached. The median interval between (153)Sm doses was 35 days (range, 27 to 57 days). The only significant toxicity was mild, transient myelosuppression. Five patients (28%) experienced grade 3 hematologic toxicity. There were no grade > or = 4 hematologic or nonhematologic toxicities.


CONCLUSIONS
Two dosing cycles consisting of weekly docetaxel and monthly (153)Sm-lexidronam were well tolerated and feasible in this CRPC population.
Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, 77239-1439, USA. stu@mdanderson.org
Shi-Ming
SM
Tu
Paul
P
Mathew
Franklin C
FC
Wong
Donnah
D
Jones
Marcella M
MM
Johnson
Christopher J
CJ
Logothetis
D000368:Aged; D000369:Aged, 80 and over; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003248:Constipation / Q000209:etiology; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005221:Fatigue / Q000209:etiology; D005240:Feasibility Studies; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009504:Neutrophils / Q000166:cytology; D009919:Orchiectomy; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010146:Pain / Q000209:etiology; D010976:Platelet Count; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000532:radiotherapy*; D011868:Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D018712:Analgesics, Non-Narcotic; D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D011868:Radioisotopes; D043823:Taxoids; D000077143:Docetaxel; C061972:samarium Sm-153 lexidronam; D017430:Prostate-Specific Antigen