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Lani · 06-23-2009, 10:48 PM

: Ann Oncol. 2008 Sep;19(9):1639-43. Epub 2008 May 7. Links
Myelotoxicity of samarium Sm 153 lexidronam in patients receiving prior treatment with chemotherapy or radiotherapy.

Heron DE, Brufsky A, Beriwal S, Kurman M.
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA. herond2@upmc.edu
BACKGROUND: The effect of prior treatment with radiotherapy and/or chemotherapy on the myelotoxicity of samarium lexidronam (Sm 153) in patients with metastatic bone lesions and bone pain was described. METHODS: Single-institution retrospective chart review of patients receiving Sm 153. The effect of Sm 153 on peripheral white blood cell (WBC), platelet counts, and change from baseline was calculated. RESULTS: The available hematologic data from records of 58 patients receiving 100 treatments with Sm 153 were reviewed. Prior treatment with radiotherapy or chemotherapy had no effect on changes from baseline or median nadir counts for either WBC or platelets when compared with patients not having such prior treatments. Multiple treatments with Sm 153 had no effect on change from baseline in WBC or platelet counts as compared with the initial administration. Median survival following the first dose of Sm 153 was 15 months. CONCLUSIONS: Prior treatment with radiotherapy or chemotherapy did not affect the rates of myelotoxicity. Multiple treatments with samarium Sm 153 lexidronam also had no effect on severity of myelotoxicity with successive courses. Patients with bone predominant metastatic disease may survive for extended periods of time and may safely be treated with multiple modalities of therapy.
PMID: 18467311 [PubMed - indexed for MEDLINE]
Links
Safety and efficacy of repeat administration of samarium Sm-153 lexidronam to patients with metastatic bone pain.

Sartor O, Reid RH, Bushnell DL, Quick DP, Ell PJ.
Lank Center for Genitourinary Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA. oliver_sartor@dfci.harvard.edu
BACKGROUND: Samarium Sm 153 lexidronam (Sm-153) is an effective and well-tolerated treatment for painful bone metastases. The purpose of the analysis was to assess the safety and efficacy of repeated doses of Sm-153 in patients with metastatic bone pain. METHODS: Data were collected prospectively for 202 patients administered 1.0 mCi/kg of Sm-153. Particular emphasis was placed on analysis of data from 55 patients receiving > or = 2 doses. Pain scores, adverse events, and hematologic parameters were assessed after each dose. RESULTS: Mild, transient suppression of platelets and white blood cell counts was the most common adverse event after treatment. Nadirs were approximately half of baseline at 4 weeks after dosing with recovery by Week 8 in 90% of patients. Temporary grade 3 thrombocytopenia occurred in 11%, 12%, and 17% of patients after the first, second, and third drug administration, respectively. Grade 3 leukopenia occurred in less than 7% of patients independent of the number of administrations. Significant decreases in pain scores (P < .001) were observed at Week 4 after each of the first 3 doses and maintained at Week 8 after the first 2 doses (P < .003) but not the third. Decreases in pain scores were observed in 70%, 63%, and 80% of patients, respectively, at Week 4 after the first 3 administrations. CONCLUSIONS: Repeated dosing of 1.0 mCi/kg of Sm-153 was both safe and effective and is a reasonable treatment option in patients whose bone pain responds and then recurs after an initial dose provided that adequate hematologic function is present at the time of drug administration. (c) 2007 American Cancer Society.
: Rev Urol. 2004;6 Suppl 10:S3-S12. Links
Overview of samarium sm 153 lexidronam in the treatment of painful metastatic bone disease.

Sartor O.
Bone pain associated with advanced prostate and other cancers is a frequent and significant complication, and the effective management of metastatic bone disease and accompanying symptoms continues to be one of the major problems facing patients and their physicians. Treatment is in part dependent on prior treatments; usually a combination of systemic and local modalities is used because no single treatment regimen is effective for an extended period of time. The 3 radionuclides currently approved for treatment of bone pain (phosphorus-32, strontium-89, and samarium-153) are discussed in this review as viable treatment options, with emphasis on the third-generation agent in this category, samarium Sm 153 lexidronam. Clinical trial data are described that support the use of this agent in patients with hormone-refractory prostate cancer with painful metastatic bone disease, and the efficacy of and role for combination therapies are also discussed.

Int J Radiat Biol. 2009 May;85(5):448-53. Links
Bone marrow recovery following use of systemic (153)Sm-lexidronam and (89)Sr-chloride for bone pain palliation after myelosuppressive therapy.

Papatheofanis FJ, Najib MM.
Department of Radiology, Rebecca and John Moores UCSD Comprehensive Cancer Center, University of California, San Diego, USA.
PURPOSE: Using plasma flt3 ((FMS (Friend murine strain))-like tyrosine kinase 3)-ligand cytokine (FL) as a biomarker, the purpose of this study was to determine whether patients receiving palliative radionuclide treatment following chemotherapy experienced enhanced myelosuppression. MATERIALS AND METHODS: A total of 48 patients with solid tumors who failed multi-agent chemotherapy were investigated; they previously received 1-3 cycles of combination chemotherapy over 4-10 months. Patients were divided into four cohorts including 10 patients with early stage solid tumors prior to chemotherapy induction (naive group), 10 patients with (non-metastatic) malignancy actively undergoing chemotherapy without radionuclide follow-up (chemotherapy-alone group), 13 patients who underwent standard (1.0 mCi/kg) dose (153)Sm ((153)samarium)-lexidronam therapy following chemotherapy ((153)Sm group), and 15 patients who underwent standard (4 mCi) dose (89)Sr ((89)strontium)-chloride therapy following chemotherapy ((89)Sr group). Plasma FL was measured using a quantitative sandwich enzyme immunoassay and CBC (complete blood count), measuring WBC (white blood cell) and PLT (platelet), was performed. RESULTS: Plasma FL concentration demonstrated a gradual decrease after chemotherapy. In patients who received (153)Sm within two weeks of completing chemotherapy, there is a distinguishable spike in FL concentration at approximately three weeks after dose administration, which precedes a decrease in WBC and PLT counts. On the other hand, a spike in FL levels in patients who received (89)Sr therapy is noted at approximately 10 weeks (p < 0.034). CONCLUSIONS: Increases in FL concentration associated with (153)Sm-lexidronam therapy following combination chemotherapy occurred earlier and returned to control levels more rapidly than did those in patients similarly treated with (89)Sr. These differences might be associated with the shorter decay half-life and lower particle emission energies of (153)Sm.
PMID: 19437245 [PubMed - in process
PMID: 16985930 [PubMed - in process]

06-23-2009, 10:48 PM	#4
Lani Senior Member Join Date: Mar 2006 Posts: 4,783	some abstracts : Ann Oncol. 2008 Sep;19(9):1639-43. Epub 2008 May 7. Links Myelotoxicity of samarium Sm 153 lexidronam in patients receiving prior treatment with chemotherapy or radiotherapy. Heron DE, Brufsky A, Beriwal S, Kurman M. Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA. herond2@upmc.edu BACKGROUND: The effect of prior treatment with radiotherapy and/or chemotherapy on the myelotoxicity of samarium lexidronam (Sm 153) in patients with metastatic bone lesions and bone pain was described. METHODS: Single-institution retrospective chart review of patients receiving Sm 153. The effect of Sm 153 on peripheral white blood cell (WBC), platelet counts, and change from baseline was calculated. RESULTS: The available hematologic data from records of 58 patients receiving 100 treatments with Sm 153 were reviewed. Prior treatment with radiotherapy or chemotherapy had no effect on changes from baseline or median nadir counts for either WBC or platelets when compared with patients not having such prior treatments. Multiple treatments with Sm 153 had no effect on change from baseline in WBC or platelet counts as compared with the initial administration. Median survival following the first dose of Sm 153 was 15 months. CONCLUSIONS: Prior treatment with radiotherapy or chemotherapy did not affect the rates of myelotoxicity. Multiple treatments with samarium Sm 153 lexidronam also had no effect on severity of myelotoxicity with successive courses. Patients with bone predominant metastatic disease may survive for extended periods of time and may safely be treated with multiple modalities of therapy. PMID: 18467311 [PubMed - indexed for MEDLINE] Links Safety and efficacy of repeat administration of samarium Sm-153 lexidronam to patients with metastatic bone pain. Sartor O, Reid RH, Bushnell DL, Quick DP, Ell PJ. Lank Center for Genitourinary Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA. oliver_sartor@dfci.harvard.edu BACKGROUND: Samarium Sm 153 lexidronam (Sm-153) is an effective and well-tolerated treatment for painful bone metastases. The purpose of the analysis was to assess the safety and efficacy of repeated doses of Sm-153 in patients with metastatic bone pain. METHODS: Data were collected prospectively for 202 patients administered 1.0 mCi/kg of Sm-153. Particular emphasis was placed on analysis of data from 55 patients receiving > or = 2 doses. Pain scores, adverse events, and hematologic parameters were assessed after each dose. RESULTS: Mild, transient suppression of platelets and white blood cell counts was the most common adverse event after treatment. Nadirs were approximately half of baseline at 4 weeks after dosing with recovery by Week 8 in 90% of patients. Temporary grade 3 thrombocytopenia occurred in 11%, 12%, and 17% of patients after the first, second, and third drug administration, respectively. Grade 3 leukopenia occurred in less than 7% of patients independent of the number of administrations. Significant decreases in pain scores (P < .001) were observed at Week 4 after each of the first 3 doses and maintained at Week 8 after the first 2 doses (P < .003) but not the third. Decreases in pain scores were observed in 70%, 63%, and 80% of patients, respectively, at Week 4 after the first 3 administrations. CONCLUSIONS: Repeated dosing of 1.0 mCi/kg of Sm-153 was both safe and effective and is a reasonable treatment option in patients whose bone pain responds and then recurs after an initial dose provided that adequate hematologic function is present at the time of drug administration. (c) 2007 American Cancer Society. : Rev Urol. 2004;6 Suppl 10:S3-S12. Links Overview of samarium sm 153 lexidronam in the treatment of painful metastatic bone disease. Sartor O. Bone pain associated with advanced prostate and other cancers is a frequent and significant complication, and the effective management of metastatic bone disease and accompanying symptoms continues to be one of the major problems facing patients and their physicians. Treatment is in part dependent on prior treatments; usually a combination of systemic and local modalities is used because no single treatment regimen is effective for an extended period of time. The 3 radionuclides currently approved for treatment of bone pain (phosphorus-32, strontium-89, and samarium-153) are discussed in this review as viable treatment options, with emphasis on the third-generation agent in this category, samarium Sm 153 lexidronam. Clinical trial data are described that support the use of this agent in patients with hormone-refractory prostate cancer with painful metastatic bone disease, and the efficacy of and role for combination therapies are also discussed. Int J Radiat Biol. 2009 May;85(5):448-53. Links Bone marrow recovery following use of systemic (153)Sm-lexidronam and (89)Sr-chloride for bone pain palliation after myelosuppressive therapy. Papatheofanis FJ, Najib MM. Department of Radiology, Rebecca and John Moores UCSD Comprehensive Cancer Center, University of California, San Diego, USA. PURPOSE: Using plasma flt3 ((FMS (Friend murine strain))-like tyrosine kinase 3)-ligand cytokine (FL) as a biomarker, the purpose of this study was to determine whether patients receiving palliative radionuclide treatment following chemotherapy experienced enhanced myelosuppression. MATERIALS AND METHODS: A total of 48 patients with solid tumors who failed multi-agent chemotherapy were investigated; they previously received 1-3 cycles of combination chemotherapy over 4-10 months. Patients were divided into four cohorts including 10 patients with early stage solid tumors prior to chemotherapy induction (naive group), 10 patients with (non-metastatic) malignancy actively undergoing chemotherapy without radionuclide follow-up (chemotherapy-alone group), 13 patients who underwent standard (1.0 mCi/kg) dose (153)Sm ((153)samarium)-lexidronam therapy following chemotherapy ((153)Sm group), and 15 patients who underwent standard (4 mCi) dose (89)Sr ((89)strontium)-chloride therapy following chemotherapy ((89)Sr group). Plasma FL was measured using a quantitative sandwich enzyme immunoassay and CBC (complete blood count), measuring WBC (white blood cell) and PLT (platelet), was performed. RESULTS: Plasma FL concentration demonstrated a gradual decrease after chemotherapy. In patients who received (153)Sm within two weeks of completing chemotherapy, there is a distinguishable spike in FL concentration at approximately three weeks after dose administration, which precedes a decrease in WBC and PLT counts. On the other hand, a spike in FL levels in patients who received (89)Sr therapy is noted at approximately 10 weeks (p < 0.034). CONCLUSIONS: Increases in FL concentration associated with (153)Sm-lexidronam therapy following combination chemotherapy occurred earlier and returned to control levels more rapidly than did those in patients similarly treated with (89)Sr. These differences might be associated with the shorter decay half-life and lower particle emission energies of (153)Sm. PMID: 19437245 [PubMed - in process PMID: 16985930 [PubMed - in process]