Article
Clinical benefit of bone-targeted radiometabolic therapy with 153Sm-EDTMP combined with chemotherapy in patients with metastatic hormone-refractory prostate cancer.
Division of Medical Oncology, Department of Oncology, University Hospital, Pisa, Italy.
European journal of nuclear medicine and molecular imaging (impact factor:
4.99).
08/2007;
34(7):1023-30.
DOI:10.1007/s00259-006-0343-8
pp.1023-30
Source: PubMed
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Citations (0)
- Cited In (5)
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Article: The use of chelated radionuclide (samarium-153-ethylenediaminetetramethylenephosphonate) to modulate phenotype of tumor cells and enhance T cell-mediated killing.
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ABSTRACT: Exposing human tumor cells to sublethal doses of external beam radiation up-regulates expression of tumor antigen and accessory molecules, rendering tumor cells more susceptible to killing by antigen-specific CTLs. This study explored the possibility that exposure to palliative doses of a radiopharmaceutical agent could alter the phenotype of tumor cells to render them more susceptible to T cell-mediated killing. Here, 10 human tumor cell lines (4 prostate, 2 breast, and 4 lung) were exposed to increasing doses of the radiopharmaceutical samarium-153-ethylenediaminetetramethylenephosphonate ((153)Sm-EDTMP) used in cancer patients to treat pain due to bone metastasis. Fluorescence-activated cell sorting analysis and quantitative real-time PCR analysis for expression of five surface molecules and several tumor-associated antigens involved in prostate cancer were done. LNCaP human prostate cancer cells were exposed to (153)Sm-EDTMP and incubated with tumor-associated antigen-specific CTL in a CTL killing assay to determine whether exposure to (153)Sm-EDTMP rendered LNCaP cells more susceptible to T cell-mediated killing. Tumor cells up-regulated the surface molecules Fas (100% of cell lines up-regulated Fas), carcinoembryonic antigen (90%), mucin-1 (60%), MHC class I (50%), and intercellular adhesion molecule-1 (40%) in response to (153)Sm-EDTMP. Quantitative real-time PCR analysis revealed additional up-regulated tumor antigens. Exposure to (153)Sm-EDTMP rendered LNCaP cells more susceptible to killing by CTLs specific for prostate-specific antigen, carcinoembryonic antigen, and mucin-1. Doses of (153)Sm-EDTMP equivalent to palliative doses delivered to bone alter the phenotype of tumor cells, suggesting that (153)Sm-EDTMP may work synergistically with immunotherapy to increase the susceptibility of tumor cells to CTL killing.Clinical Cancer Research 08/2008; 14(13):4241-9. · 7.74 Impact Factor -
Article: (188)Re-HEDP combined with capecitabine in hormone-refractory prostate cancer patients with bone metastases: a phase I safety and toxicity study.
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ABSTRACT: (188)Re-HEDP is indicated for the treatment of pain in patients with painful osteoblastic bone metastases, including hormone-refractory prostate cancer patients. Efficacy may be improved by adding chemotherapy to the treatment regimen as a radiation sensitizer. The combination of (188)Re-HEDP and capecitabine (Xeloda(R)) was tested in a clinical phase I study. Patients with hormone-refractory prostate cancer were treated with capecitabine for 14 days (oral twice daily in a dose escalation regimen with steps of 1/3 of 2,500 mg/m(2) per day in cohorts of three to six patients, depending on toxicity). Two days later patients were treated with 37 MBq/kg (188)Re-HEDP as an intravenous injection. Six hours after treatment post-therapy scintigraphy was performed. Urine was collected for 8 h post-injection. Follow-up was at least 8 weeks. The primary end-point was to establish the maximum tolerable dose (MTD) of capecitabine when combined with (188)Re-HEDP. Secondary end-points included the effect of capecitabine on the biodistribution and pharmacokinetics of (188)Re-HEDP. Three patients were treated in the first and second cohorts, each without unacceptable toxicity. One of six patients in the highest cohort experienced unacceptable toxicity (grade 4 thrombopaenia). The MTD proved to be the maximum dose of 2,500 mg/m(2) per day capecitabine. No unexpected toxicity occurred. Capecitabine had no effect on uptake or excretion of (188)Re-HEDP. Capecitabine may be safely used in combination with (188)Re-HEDP in a dose of 2,500 mg/m(2) per day and 37 MBq/kg, respectively. Efficacy will be further studied in a phase II study using these dosages.European Journal of Nuclear Medicine 04/2009; 36(9):1425-33. · 4.53 Impact Factor -
Article: Phase I trial with a combination of docetaxel and ¹⁵³Sm-lexidronam in patients with castration-resistant metastatic prostate cancer.
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ABSTRACT: This study was designed to evaluate toxicity and preliminary efficacy of 2 cycles of concomitant standard dose/schedule of (153)Sm-lexidronam plus Q 3 weeks schedule escalating doses of docetaxel in metastatic castration-resistant prostate cancer (mCRPC). 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). (153)Sm-lexidronam was administered on days 2 (Q 12 weeks) at dose of 1 mCi/kg/cycle (maximum of 2 cycles). Thirteen patients received an average of 3.6 doses of docetaxel (range, 2-6 doses, median 4) and 1.5 doses of (153)Sm-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. 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 (153)Sm-lexidronam is feasible with reversible bone marrow suppression, and deserves further testing in mCRPC patients with extensive bone metastasis.Urologic Oncology 12/2009; 29(6):670-5. · 3.22 Impact Factor
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Keywords
10 months
11 months
14 patients
153Sm-ethylenediaminetetramethylene phosphonate
16 patients
20 patients
25 patients
30 months
30 patients
45 patients
5 months
6 patients
additive adverse effects
additive toxicities
common observations
Haematological toxicities
hormone-refractory prostate cancer
HRPC patients
metastatic bone sites
pain relief