A Phase I/II study of strontium-89 combined with gemcitabine in the treatment of patients with androgen independent prostate carcinoma and bone metastases.
BACKGROUND
The objectives of the current study were to determine the maximum tolerated dose and to evaluate the efficacy of gemcitabine given in combination with strontium-89 to patients with androgen independent prostate carcinoma.


METHODS
Patients with androgen-independent prostate carcinoma and painful osteoblastic bone metastases were eligible. On a 12-week course, patients received gemcitabine (600 mg/m(2) or 800 mg/m(2)) on Days 1, 8, 15, 43, 50, and 57. A single dose of strontium-89 (55 microCi/kg) was administered on Day 8.


RESULTS
Fifteen patients were registered, and all were assessable for response and toxicity. Four patients were treated at Dose Level 1 (gemcitabine 600 mg/m(2)) without dose-limiting toxicity. Eleven patients received a total of 13 courses at Dose Level 2 (gemcitabine 800 mg/m(2)). Platelet nadirs of 25000-50000 platelets per microL were common at Dose Level 2, and 1 patient had Grade 4 thrombocytopenia that was dose-limiting. Granulocyte nadirs up to < 500 granulocytes per microL occurred in 4 patients at Dose Level 2 and were reversible. There were no responses, as measured by prostate specific antigen concentration, although 6 patients (40%) had stable disease.


CONCLUSIONS
The authors concluded that 800 mg/m(2) gemcitabine was the maximum tolerated dose for the combination. The study was terminated on the basis that an overall response rate > than 10% was unlikely. Further study at this dose level and schedule is not warranted. .
Pagliaro
Lance C
LC
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. lpagliar@mdanderson.org
Delpassand
Ebrahim S
ES
Williams
Dallas
D
Millikan
Randall E
RE
Tu
Shi-Ming
SM
Logothetis
Christopher J
CJ
D000368:Aged; D001859:Bone Neoplasms / Q000556:secondary* / Q000628:therapy*; D002277:Carcinoma / Q000628:therapy; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use* / Q000633:toxicity; D004334:Drug Administration Schedule; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000628:therapy; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000628:therapy*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D013324:Strontium / Q000627:therapeutic use*; D013326:Strontium Radioisotopes / Q000627:therapeutic use*; D013739:Testosterone / Q000494:pharmacology; D000093542:Gemcitabine
D011838:Radiation-Sensitizing Agents; D013326:Strontium Radioisotopes; D003841:Deoxycytidine; D013739:Testosterone; D017430:Prostate-Specific Antigen; C025700:strontium chloride; D013324:Strontium; D000093542:Gemcitabine