Repetitively dosed docetaxel and 153samarium-EDTMP as an antitumor strategy for metastatic castration-resistant prostate cancer Journal Article

Authors: Autio, K. A.; Pandit-Taskar, N.; Carrasquillo, J. A.; Stephenson, R. D.; Slovin, S. F.; Rathkopf, D. E.; Hong, C.; Heller, G.; Scher, H. I.; Larson, S. M.; Morris, M. J.
Article Title: Repetitively dosed docetaxel and 153samarium-EDTMP as an antitumor strategy for metastatic castration-resistant prostate cancer
Abstract: Background β-emitting bone-seeking radiopharmaceuticals have historically been administered for pain palliation whereas docetaxel prolongs life in patients with metastatic castration-resistant prostate cancer (mCRPC). In combination, these agents simultaneously target the bone stroma and cancer cell to optimize antitumor effects. The toxicity and efficacy when each agent is combined at full, recommended doses, in a repetitive fashion is not well established. Methods Patients with progressive mCRPC and ≥3 bone lesions received 153Sm-EDTMP (samarium-153 ethylene diamine tetramethylene phosphonate) at a dose of 1.0 mCi/kg every 9 weeks and docetaxel at a dose of 75 mg/m2 every 3 weeks. In the absence of unacceptable toxicity, patients were allowed to continue additional cycles, defined by 9 weeks of treatment, until intolerance or biochemical/radiographic disease progression. Results Of the 30 patients treated, approximately 50% were considered to be taxane-naive, 36.7% were taxane-refractory, and 13.3% had previously been exposed to taxanes but were not considered refractory. Patients received on average 2.5 cycles of treatment (6.5 doses of docetaxel and 2.5 doses of 153Sm-EDTMP). Twelve patients (40%) demonstrated a decline in their prostate-specific antigen level of ≥50%. The median progression-free survival (biochemical or radiographic) was 7.0 months and the overall survival was 14.3 months. Nine patients (30%) did not recover platelet counts >100 K/mm 3 after a median of 3 cycles to allow for additional treatment, with 4 patients experiencing prolonged thrombocytopenia. The most common reasons for trial discontinuation were progressive disease and hematologic toxicity. Conclusions The results of the current study indicate that 153Sm- EDTMP can be safely combined with docetaxel at full doses on an ongoing basis in patients with mCRPC. Although thrombocytopenia limited therapy for some patients, preliminary efficacy supports the strategy of combining a radiopharmaceutical with chemotherapy, which is an appealing strategy given the anticipated availability of α emitters that can prolong survival. © 2013 American Cancer Society.
Keywords: adult; cancer survival; clinical article; controlled study; treatment outcome; aged; aged, 80 and over; bone neoplasms; disease-free survival; middle aged; fracture; overall survival; constipation; fatigue; neutropenia; cancer growth; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; side effect; treatment duration; cancer radiotherapy; chemotherapy; neoplasm staging; anorexia; prostate specific antigen; progression free survival; multiple cycle treatment; pain; sensory neuropathy; thrombocyte; thrombocytopenia; antineoplastic combined chemotherapy protocols; kidney failure; antineoplastic activity; docetaxel; coughing; dyspnea; febrile neutropenia; prostate cancer; prostate-specific antigen; prostatic neoplasms; severity of illness index; neutrophil; disease progression; thrombosis; drug response; muscle weakness; peripheral edema; taxoids; external beam radiotherapy; orchiectomy; taxane derivative; embolism; radioisotopes; heart atrium fibrillation; cholecystitis; leukocyte; organometallic compounds; hemoglobins; supraventricular tachycardia; alendronic acid; repeated drug dose; zoledronic acid; platelet count; hair loss; blood platelets; organophosphorus compounds; lexidronam samarium sm 153; faintness; radiopharmaceutical; 153sm-edtmp (samarium-153 ethylene diamine tetramethylene phosphonate); bladder bleeding
Journal Title: Cancer
Volume: 119
Issue: 17
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2013-09-01
Start Page: 3186
End Page: 3194
Language: English
DOI: 10.1002/cncr.28103
PROVIDER: scopus
PMCID: PMC3775970
PUBMED: 23765638
Notes: --- - "Export Date: 1 October 2013" - "CODEN: CANCA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Glenn Heller
    303 Heller
  2. Susan Slovin
    186 Slovin
  3. Michael Morris
    280 Morris
  4. Karen Anne Autio
    52 Autio
  5. Dana Elizabeth Rathkopf
    144 Rathkopf
  6. Steven M Larson
    778 Larson
  7. Howard Scher
    834 Scher
  8. Christina T Hong
    5 Hong