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


Authors: 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.
Article Title: Phase I study of samarium-153 lexidronam with docetaxel in castration-resistant metastatic prostate cancer
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 (Sm-153) 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 Sm-153 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 Sm-153-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 Sm-153-EDTMP. Patients received an average of 5.6 docetaxel doses ( range, one to 13 doses) and 2.9 Sm-153-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 Sm-153-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-naive disease may differ from those optimal for patients with taxane-resistant disease.
Keywords: prednisone; mitoxantrone; carcinoma; bone; safety; men; markers
Journal Title: Journal of Clinical Oncology
Volume: 27
Issue: 15
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2009-05-01
Start Page: 2436
End Page: 2442
Language: English
ACCESSION: ISI:000266195400007
DOI: 10.1200/jco.2008.20.4164
PROVIDER: wos
PMCID: PMC2684850
PUBMED: 19364960
Notes: --- - Article - "Source: Wos"
Altmetric Score
MSK Authors
  1. Glenn Heller
    286 Heller
  2. Susan Slovin
    181 Slovin
  3. Michael Morris
    260 Morris
  4. David Solit
    421 Solit
  5. Xiaoyu Jia
    44 Jia
  6. Lawrence H Schwartz
    277 Schwartz
  7. Dana Elizabeth Rathkopf
    137 Rathkopf
  8. Steven M Larson
    742 Larson
  9. Howard Scher
    792 Scher
  10. Christina T Hong
    5 Hong