Skip to main content
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 7/2007

01.07.2007 | Original article

Clinical benefit of bone-targeted radiometabolic therapy with 153Sm-EDTMP combined with chemotherapy in patients with metastatic hormone-refractory prostate cancer

verfasst von: Sergio Ricci, Giuseppe Boni, Ilaria Pastina, Dario Genovesi, Claudia Cianci, Serena Chiacchio, Cinzia Orlandini, Mariano Grosso, Abedallatif AlSharif, Aldo Chioni, Samantha Di Donato, Francesco Francesca, Cesare Selli, Domenico Rubello, Giuliano Mariani

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 7/2007

Einloggen, um Zugang zu erhalten

Abstract

Background

Bone metastases are responsible for most of the morbidity associated with hormone-refractory prostate cancer (HRPC). 153Sm-ethylenediaminetetramethylene phosphonate (153Sm-EDTMP) has been approved for palliation of painful skeletal metastases. We retrospectively investigated the possible synergistic effect on survival of 153Sm-EDTMP (given to HRPC patients for bone pain palliation) and chemotherapy.

Methods

Forty-five HRPC patients were evaluated, with a median age of 71 years. The number of metastatic bone sites was ≤10 in 25 patients and >10 in 20 patients. Median serum PSA was 224 ng/ml. Bone pain was mild in 6 patients, moderate in 16, severe in 22 and intolerable in 1. Fifteen patients were only treated with 153Sm-EDTMP (group A), while 30 patients also received chemotherapy (estramustine phosphate or mitoxantrone plus prednisone) at variable times: between 3 and 5 months after 153Sm-EDTMP (14 patients, group B) or within 1 month after 153Sm-EDTMP (16 patients, group C).

Results

Haematological toxicities observed after either regimen were in general mild, consistent with common observations after either 153Sm-EDTMP or chemotherapy, and without any additive adverse effects in the patients receiving both 153Sm-EDTMP and chemotherapy. Bone pain palliation to some degree was induced by 153Sm-EDTMP in 32/45 patients (71.1%), the proportion of patients with a favourable clinical response being significantly higher in group C than in group A (87.5% vs 53.3%, p = 0.0388). Also in terms of biochemical response (serum PSA levels), patients of group C performed significantly better than patients of group A (p = 0.0235). Overall median survival from the time of administration of 153Sm-EDTMP was 15 months in the total cohort of 45 patients, and was significantly longer in group C than in either group B (30 months vs 11 months, p = 0.023) or group A (30 months vs 10 months, p = 0.008).

Conclusion

The results of this study confirm that 153Sm-EDTMP is effective in terms of pain relief and PSA response, with minimal toxicity. When it was administered in combination with chemotherapy, prolonged survival indicated actual clinical benefit, while there were no additive toxicities. These results provide the rationale for future prospective evaluation of combined therapeutic strategies.
Literatur
1.
Zurück zum Zitat Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ. Cancer statistics, 2003. CA Cancer J Clin 2003;53:5–26.PubMedCrossRef Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ. Cancer statistics, 2003. CA Cancer J Clin 2003;53:5–26.PubMedCrossRef
2.
Zurück zum Zitat McRea LE, Karafin L. Carcinoma of the prostate: metastases, therapy, and survival—A statistical analysis of 500 cases. Int Coll Surg J 1958;29:723–8. McRea LE, Karafin L. Carcinoma of the prostate: metastases, therapy, and survival—A statistical analysis of 500 cases. Int Coll Surg J 1958;29:723–8.
3.
Zurück zum Zitat Tannock IF, Osoba D, Stockler MR, Ernst DS, Neville AJ, Moore MJ, et al. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol 1996;14:1756–64.PubMed Tannock IF, Osoba D, Stockler MR, Ernst DS, Neville AJ, Moore MJ, et al. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol 1996;14:1756–64.PubMed
4.
Zurück zum Zitat Sabbatini P, Larson SM, Kremer A, Zhang ZF, Sun M, Yeung H, et al. Prognostic significance of extent of disease in bone in patients with androgen-independent prostate cancer. J Clin Oncol 1999;17:948–57.PubMed Sabbatini P, Larson SM, Kremer A, Zhang ZF, Sun M, Yeung H, et al. Prognostic significance of extent of disease in bone in patients with androgen-independent prostate cancer. J Clin Oncol 1999;17:948–57.PubMed
5.
Zurück zum Zitat Carroll PR, Kantoff PW, Balk SP, Brown MA, D’amico AV, George DJ, et al. Overview consensus statement. Newer approaches to androgen deprivation therapy in prostate cancer. Urology 2002;60 suppl 1:1–6.PubMedCrossRef Carroll PR, Kantoff PW, Balk SP, Brown MA, D’amico AV, George DJ, et al. Overview consensus statement. Newer approaches to androgen deprivation therapy in prostate cancer. Urology 2002;60 suppl 1:1–6.PubMedCrossRef
6.
Zurück zum Zitat Chodak GW, Keane T, Klotz L. Critical evaluation of hormonal therapy for carcinoma of the prostate. Urology 2002;60:201–8.PubMedCrossRef Chodak GW, Keane T, Klotz L. Critical evaluation of hormonal therapy for carcinoma of the prostate. Urology 2002;60:201–8.PubMedCrossRef
7.
Zurück zum Zitat Tannock IF. Is there evidence that chemotherapy is of benefit to patients with carcinoma of the prostate? J Clin Oncol 1985;3:1013–21.PubMed Tannock IF. Is there evidence that chemotherapy is of benefit to patients with carcinoma of the prostate? J Clin Oncol 1985;3:1013–21.PubMed
8.
Zurück zum Zitat Eisenberger MA, Simon R, O’Dwyer PJ, Wittes RE, Friedman MA. A reevaluation of nonhormonal cytotoxic chemotherapy in treatment of prostatic carcinoma. J Clin Oncol 1985;3:827–41.PubMed Eisenberger MA, Simon R, O’Dwyer PJ, Wittes RE, Friedman MA. A reevaluation of nonhormonal cytotoxic chemotherapy in treatment of prostatic carcinoma. J Clin Oncol 1985;3:827–41.PubMed
9.
Zurück zum Zitat Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004;351:1502–12.PubMedCrossRef Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004;351:1502–12.PubMedCrossRef
10.
Zurück zum Zitat Petrylak DP, Tangen CM, Hussain MHA, Lara PN Jr, Jones JA, Taplin ME, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004;351:1513–20.PubMedCrossRef Petrylak DP, Tangen CM, Hussain MHA, Lara PN Jr, Jones JA, Taplin ME, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004;351:1513–20.PubMedCrossRef
11.
Zurück zum Zitat Serafini AN. Therapy of metastic bone pain. J Nucl Med 2001;42:895–906.PubMed Serafini AN. Therapy of metastic bone pain. J Nucl Med 2001;42:895–906.PubMed
12.
Zurück zum Zitat Lewington VJ. Bone-seeking radionuclides for therapy. J Nucl Med 2005;46:38S–47S.PubMed Lewington VJ. Bone-seeking radionuclides for therapy. J Nucl Med 2005;46:38S–47S.PubMed
13.
Zurück zum Zitat Pandit-Taskar N, Batraki M, Divgi R. Radiopharmaceutical therapy for palliation of bone pain from osseous metastases. J Nucl Med 2004;45:1358–65.PubMed Pandit-Taskar N, Batraki M, Divgi R. Radiopharmaceutical therapy for palliation of bone pain from osseous metastases. J Nucl Med 2004;45:1358–65.PubMed
14.
Zurück zum Zitat Dafermou A, Colamussi P, Giganti M, Cittanti C, Bestagno M, Piffanelli A. A multicentre observational study of radionuclide therapy in patients with painful bone metastases of prostate cancer. Eur J Nucl Med 2001;28:788–98.PubMedCrossRef Dafermou A, Colamussi P, Giganti M, Cittanti C, Bestagno M, Piffanelli A. A multicentre observational study of radionuclide therapy in patients with painful bone metastases of prostate cancer. Eur J Nucl Med 2001;28:788–98.PubMedCrossRef
15.
Zurück zum Zitat Serafini AN. Systemic metabolic radiotherapy with samarium-153-EDTMP for the treatment of painful bone metastasis. Quart J Nucl Med 2001;45:91–9. Serafini AN. Systemic metabolic radiotherapy with samarium-153-EDTMP for the treatment of painful bone metastasis. Quart J Nucl Med 2001;45:91–9.
16.
Zurück zum Zitat Serafini AN. Samarium Sm-153 lexidronam for the palliation of bone pain associated with metastasis. Cancer 2000;88 suppl:2934–9.PubMedCrossRef Serafini AN. Samarium Sm-153 lexidronam for the palliation of bone pain associated with metastasis. Cancer 2000;88 suppl:2934–9.PubMedCrossRef
17.
Zurück zum Zitat Serafini AN, Houston SJ, Resche I, Quick DP, Grund FM, Ell PJ, et al. Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double blind placebo-controlled clinical trial. J Clin Oncol 1998;16:1574–81.PubMed Serafini AN, Houston SJ, Resche I, Quick DP, Grund FM, Ell PJ, et al. Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double blind placebo-controlled clinical trial. J Clin Oncol 1998;16:1574–81.PubMed
18.
Zurück zum Zitat Sartor O, Reid R, Hoskin PJ, Quick DP, Ell PJ, Coleman RE, et al. Samarium-153-lexidronam complex for treatment of painful bone metastases in hormone-refractory prostate cancer. Urology 2004;63:940–5.PubMedCrossRef Sartor O, Reid R, Hoskin PJ, Quick DP, Ell PJ, Coleman RE, et al. Samarium-153-lexidronam complex for treatment of painful bone metastases in hormone-refractory prostate cancer. Urology 2004;63:940–5.PubMedCrossRef
19.
Zurück zum Zitat Resche I, Chatal JF, Pecking A, Ell P, Duchesne G, Rubens R, et al. A dose-controlled study of Sm-153-EDTMP in the treatment of patients with painful bone metastasis. Eur J Cancer 1997;33:1583–91.PubMedCrossRef Resche I, Chatal JF, Pecking A, Ell P, Duchesne G, Rubens R, et al. A dose-controlled study of Sm-153-EDTMP in the treatment of patients with painful bone metastasis. Eur J Cancer 1997;33:1583–91.PubMedCrossRef
20.
Zurück zum Zitat Sinzinger H, Weiss K, Granegger S, Ofluogu S, Kratzik CH, Hajek CH. The Vienna protocol on repeated low dose 153Sm-EDTMP therapy includes pain palliation and lesion regression/stabilization (abstract). Eur J Nucl Med 2001;28:1198. Sinzinger H, Weiss K, Granegger S, Ofluogu S, Kratzik CH, Hajek CH. The Vienna protocol on repeated low dose 153Sm-EDTMP therapy includes pain palliation and lesion regression/stabilization (abstract). Eur J Nucl Med 2001;28:1198.
21.
Zurück zum Zitat Riva P, Franceschi G, Riva N, Casi M, Santimaria M. Anti-tumor effectiveness of multiple courses of 153Sm-EDTMP in bone metastasis from different cancers (abstract). Eur J Nucl Med 2001;28:1054. Riva P, Franceschi G, Riva N, Casi M, Santimaria M. Anti-tumor effectiveness of multiple courses of 153Sm-EDTMP in bone metastasis from different cancers (abstract). Eur J Nucl Med 2001;28:1054.
22.
Zurück zum Zitat Akerley W, Butera J, Wehbe T, Noto R, Stein B, Safran H, et al. A multiinstitutional, concurrent chemoradiation trial of strontium-89 extramustine and vinblastine for hormone refractory prostate carcinoma involving bone. Cancer 2002;94:1654–60.PubMedCrossRef Akerley W, Butera J, Wehbe T, Noto R, Stein B, Safran H, et al. A multiinstitutional, concurrent chemoradiation trial of strontium-89 extramustine and vinblastine for hormone refractory prostate carcinoma involving bone. Cancer 2002;94:1654–60.PubMedCrossRef
23.
Zurück zum Zitat Sciuto R, Festa A, Rea S, Pasqualoni R, Bergomi S, Petrilli G, et al. Effects of low-dose cisplatin on 89Sr therapy for painful bone metastases from prostate cancer: a randomized clinical trial. J Nucl Med 2002;43:79–86.PubMed Sciuto R, Festa A, Rea S, Pasqualoni R, Bergomi S, Petrilli G, et al. Effects of low-dose cisplatin on 89Sr therapy for painful bone metastases from prostate cancer: a randomized clinical trial. J Nucl Med 2002;43:79–86.PubMed
24.
Zurück zum Zitat Pagliaro LC, Delpassand ES, Williams D, Millikan RE, Tu SM, Logothetis CJ. A phase I/II study of strontium-89 combined with gemcitabine in the treatment of patients with androgen independent prostate carcinoma and bone metastases. Cancer 2003;12:2988–94.CrossRef Pagliaro LC, Delpassand ES, Williams D, Millikan RE, Tu SM, Logothetis CJ. A phase I/II study of strontium-89 combined with gemcitabine in the treatment of patients with androgen independent prostate carcinoma and bone metastases. Cancer 2003;12:2988–94.CrossRef
25.
Zurück zum Zitat Logothetis C, Tu S, Navone N. Targeting prostate cancer bone metastases. Cancer 2003;97:785–8.PubMedCrossRef Logothetis C, Tu S, Navone N. Targeting prostate cancer bone metastases. Cancer 2003;97:785–8.PubMedCrossRef
26.
Zurück zum Zitat Valdés Olmos RA, Hoefnagel CA. Radionuclide therapy in oncology: the dawning of its concomitant use with other modalities? Eur J Nucl Med Mol Imaging 2004;31:929–31.PubMed Valdés Olmos RA, Hoefnagel CA. Radionuclide therapy in oncology: the dawning of its concomitant use with other modalities? Eur J Nucl Med Mol Imaging 2004;31:929–31.PubMed
27.
Zurück zum Zitat Tu S, Millikan RE, Mengistu B, Delpassand ES, Amato RJ, Pagliaro LC, et al. Bone-targeted therapy for advanced androgen independent carcinoma of the prostate: a randomised phase II trial. Lancet 2001;367:336–41CrossRef Tu S, Millikan RE, Mengistu B, Delpassand ES, Amato RJ, Pagliaro LC, et al. Bone-targeted therapy for advanced androgen independent carcinoma of the prostate: a randomised phase II trial. Lancet 2001;367:336–41CrossRef
28.
Zurück zum Zitat Palmedo H, Manka-Waluch A, Albers P, Schmidt-Wolf IG, Reinhardt M, Ezziddin S, et al. Repeated bone-targeted therapy for hormone-refractory prostate carcinoma: randomized phase II trial with the new, high-energy radiopharmaceutical rhenium-188 hydroxyethylidene-diphosphonate. J Clin Oncol 2003;21:2869–75.PubMedCrossRef Palmedo H, Manka-Waluch A, Albers P, Schmidt-Wolf IG, Reinhardt M, Ezziddin S, et al. Repeated bone-targeted therapy for hormone-refractory prostate carcinoma: randomized phase II trial with the new, high-energy radiopharmaceutical rhenium-188 hydroxyethylidene-diphosphonate. J Clin Oncol 2003;21:2869–75.PubMedCrossRef
29.
Zurück zum Zitat Palmedo H, Bucerius J. Radionuclide therapy in oncology: repeated administrations of high dose rate radiopharmaceuticals (abstract). Eur J Nucl Med Mol Imaging 2004;31:1556.PubMedCrossRef Palmedo H, Bucerius J. Radionuclide therapy in oncology: repeated administrations of high dose rate radiopharmaceuticals (abstract). Eur J Nucl Med Mol Imaging 2004;31:1556.PubMedCrossRef
30.
Zurück zum Zitat Anderson P. Samarium for osteoblastic bone metastases and osteosarcoma. Expert Opin Pharmacother 2006;7:1475–86.PubMedCrossRef Anderson P. Samarium for osteoblastic bone metastases and osteosarcoma. Expert Opin Pharmacother 2006;7:1475–86.PubMedCrossRef
31.
Zurück zum Zitat Anderson PM, Wiseman GA, Erlandson L, Rodriguez V, Trotz B, Dubansky SA, et al. Gemcitabine radiosensitization after high-dose samarium for osteoblastic osteosarcoma. Clin Cancer Res 2005;11:6895–900.PubMedCrossRef Anderson PM, Wiseman GA, Erlandson L, Rodriguez V, Trotz B, Dubansky SA, et al. Gemcitabine radiosensitization after high-dose samarium for osteoblastic osteosarcoma. Clin Cancer Res 2005;11:6895–900.PubMedCrossRef
32.
Zurück zum Zitat Rodriguez V, Erlandson L, Arndt CAS, Wiseman GA, Anderson PM. Low toxicity and efficacy of 153samarium-EDTMP and melphalan as a conditioning regimen for secondary acute myelogenous leukemia. Pediatr Transplantation 2005;9:122–6.CrossRef Rodriguez V, Erlandson L, Arndt CAS, Wiseman GA, Anderson PM. Low toxicity and efficacy of 153samarium-EDTMP and melphalan as a conditioning regimen for secondary acute myelogenous leukemia. Pediatr Transplantation 2005;9:122–6.CrossRef
33.
Zurück zum Zitat Knop S, Dohmer BM, Kanz L, Bares R, Einsele H. 153 Samarium-EDTMP in myeloablative dosage followed by a second autotransplantation in patients with relapsed multiple myeloma (abstract). Haematologica 2004;89:ECR36.PubMed Knop S, Dohmer BM, Kanz L, Bares R, Einsele H. 153 Samarium-EDTMP in myeloablative dosage followed by a second autotransplantation in patients with relapsed multiple myeloma (abstract). Haematologica 2004;89:ECR36.PubMed
34.
Zurück zum Zitat Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC. Natural history of progression after PSA elevation following radical prostatectomy. JAMA 1999;281:1591–7.PubMedCrossRef Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC. Natural history of progression after PSA elevation following radical prostatectomy. JAMA 1999;281:1591–7.PubMedCrossRef
35.
Zurück zum Zitat Berry S, Waldron T, Winquist E, Lukka H. The use of bisphosphonates in men with hormone-refractory prostate cancer: a systematic review of randomized trials. Can J Urol 2006;13:3180–8.PubMed Berry S, Waldron T, Winquist E, Lukka H. The use of bisphosphonates in men with hormone-refractory prostate cancer: a systematic review of randomized trials. Can J Urol 2006;13:3180–8.PubMed
36.
Zurück zum Zitat Storto G, Klain M, Paone G, Liuzzi R, Molino L, Marinelli A, et al. Combined therapy with Sr-89 and zoledronic acid in patients with painful bone metastases. Bone 2006;39:35–41.PubMedCrossRef Storto G, Klain M, Paone G, Liuzzi R, Molino L, Marinelli A, et al. Combined therapy with Sr-89 and zoledronic acid in patients with painful bone metastases. Bone 2006;39:35–41.PubMedCrossRef
37.
Zurück zum Zitat Laplanche A, Beuzeboc P, Lumbroso J, Di Palma M, Theodore C, Prapotnich D, et al. A phase II trial of docetaxel and samarium in patients with bone metastases from castration-refractory prostate cancer (CRPC) and a response or stabilization after induction docetaxel-estramustine (abstract). Proc Am Soc Clin Oncol 2006;24:4608. Laplanche A, Beuzeboc P, Lumbroso J, Di Palma M, Theodore C, Prapotnich D, et al. A phase II trial of docetaxel and samarium in patients with bone metastases from castration-refractory prostate cancer (CRPC) and a response or stabilization after induction docetaxel-estramustine (abstract). Proc Am Soc Clin Oncol 2006;24:4608.
38.
Zurück zum Zitat Widmark A, Linne T, Modig H, Johansson L. Optimizing the time of co-administration of docetaxel and samarium-153 for advanced androgen independent carcinoma of the prostate (abstract). Proc Am Soc Clin Oncol 2003;22:433. Widmark A, Linne T, Modig H, Johansson L. Optimizing the time of co-administration of docetaxel and samarium-153 for advanced androgen independent carcinoma of the prostate (abstract). Proc Am Soc Clin Oncol 2003;22:433.
Metadaten
Titel
Clinical benefit of bone-targeted radiometabolic therapy with 153Sm-EDTMP combined with chemotherapy in patients with metastatic hormone-refractory prostate cancer
verfasst von
Sergio Ricci
Giuseppe Boni
Ilaria Pastina
Dario Genovesi
Claudia Cianci
Serena Chiacchio
Cinzia Orlandini
Mariano Grosso
Abedallatif AlSharif
Aldo Chioni
Samantha Di Donato
Francesco Francesca
Cesare Selli
Domenico Rubello
Giuliano Mariani
Publikationsdatum
01.07.2007
Verlag
Springer-Verlag
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 7/2007
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-006-0343-8

Weitere Artikel der Ausgabe 7/2007

European Journal of Nuclear Medicine and Molecular Imaging 7/2007 Zur Ausgabe

Society communications

Society communications

Letter to the editor

Reply

Letter to the editor

Reply