Phase I trial with a combination of docetaxel and 153Sm-lexidronam in patients with castration-resistant metastatic prostate cancer

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Abstract

Background: This study was designed to evaluate toxicity and preliminary efficacy of 2 cycles of concomitant standard dose/schedule of 153Sm-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. 153Sm-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 153Sm-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 153Sm-lexidronam is feasible with reversible bone marrow suppression, and deserves further testing in mCRPC patients with extensive bone metastasis.

Original languageEnglish (US)
Pages (from-to)670-675
Number of pages6
JournalUrologic Oncology: Seminars and Original Investigations
Volume29
Issue number6
DOIs
StatePublished - Nov 2011

Fingerprint

docetaxel
Castration
Prostatic Neoplasms
Appointments and Schedules
Bone and Bones
Neoplasm Metastasis
Bone Diseases
Neutropenia
Disease Progression
Bone Marrow

Keywords

  • Sm-lexidronam
  • Docetaxel
  • Metastatic prostate cancer
  • Phase I

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

@article{0cce1d4936384d0785d37e262379caa0,
title = "Phase I trial with a combination of docetaxel and 153Sm-lexidronam in patients with castration-resistant metastatic prostate cancer",
abstract = "Background: This study was designed to evaluate toxicity and preliminary efficacy of 2 cycles of concomitant standard dose/schedule of 153Sm-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. 153Sm-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 153Sm-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 153Sm-lexidronam is feasible with reversible bone marrow suppression, and deserves further testing in mCRPC patients with extensive bone metastasis.",
keywords = "Sm-lexidronam, Docetaxel, Metastatic prostate cancer, Phase I",
author = "Jianqing Lin and Victoria Sinibaldi and Carducci, {Michael A} and Denmeade, {Samuel R} and Song, {Danny Y} and Theodore DeWeese and Mario Eisenberger",
year = "2011",
month = "11",
doi = "10.1016/j.urolonc.2009.10.003",
language = "English (US)",
volume = "29",
pages = "670--675",
journal = "Urologic Oncology",
issn = "1078-1439",
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number = "6",

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T1 - Phase I trial with a combination of docetaxel and 153Sm-lexidronam in patients with castration-resistant metastatic prostate cancer

AU - Lin, Jianqing

AU - Sinibaldi, Victoria

AU - Carducci, Michael A

AU - Denmeade, Samuel R

AU - Song, Danny Y

AU - DeWeese, Theodore

AU - Eisenberger, Mario

PY - 2011/11

Y1 - 2011/11

N2 - Background: This study was designed to evaluate toxicity and preliminary efficacy of 2 cycles of concomitant standard dose/schedule of 153Sm-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. 153Sm-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 153Sm-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 153Sm-lexidronam is feasible with reversible bone marrow suppression, and deserves further testing in mCRPC patients with extensive bone metastasis.

AB - Background: This study was designed to evaluate toxicity and preliminary efficacy of 2 cycles of concomitant standard dose/schedule of 153Sm-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. 153Sm-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 153Sm-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 153Sm-lexidronam is feasible with reversible bone marrow suppression, and deserves further testing in mCRPC patients with extensive bone metastasis.

KW - Sm-lexidronam

KW - Docetaxel

KW - Metastatic prostate cancer

KW - Phase I

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