Nuklearmedizin 2018; 57(05): 174-180
DOI: 10.3413/Nukmed-0989-18-07
Original Article
Georg Thieme Verlag KG Stuttgart · New York

153Sm-EDTMP and 177Lu-EDTMP are equally safe and effective in pain palliation from skeletal metastases

A randomized double-blind clinical trial 153Sm-EDTMP und 177Lu-EDTMP sind gleichermaßen sicher und wirksam bei der Schmerzlinderung von SkelettmetastasenEine randomisierte, doppelblinde klinische Studie
Mehrdad Taheri
1   Anesthesiology Research Center (Division of Pain Management), Shahid Beheshti University of Medical Sciences, Tehran, Iran
,
Zahra Azizmohammadi
2   Department of Nuclear Medicine, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
,
Mojtaba Ansari
2   Department of Nuclear Medicine, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
,
Payman Dadkhah
1   Anesthesiology Research Center (Division of Pain Management), Shahid Beheshti University of Medical Sciences, Tehran, Iran
,
Kasra Dehghan
1   Anesthesiology Research Center (Division of Pain Management), Shahid Beheshti University of Medical Sciences, Tehran, Iran
,
Rohollah Valizadeh
3   Department of Epidemiology, Iran University of Medical Sciences, Tehran, Iran
,
Majid Assadi
4   The Persian Gulf Nuclear Medicine Research Center , Bushehr University of Medical Sciences, Bushehr, Iran
› Author Affiliations
This study was supported by Shahid Beheshti University of Medical Sciences (grant no. 12605).
Further Information

Publication History

received: 30 July 2018

accepted: 20 August 2018

Publication Date:
28 September 2018 (online)

Summary

Introduction: Bone pain from multifocal blastic or mixed lytic-blastic metastatic lesions can be effectively addressed with radiopharmaceuticals with high affinity for such foci. 153Sm-ethylene diamine tetramethylene phosphonic acid (153Sm-EDTMP) and 177Lu-ethylene diamine tetramethylene phosphonic acid) (177Lu-EDTMP) are two such radiopharmaceuticals. The aim of this study was to make a comparison of efficacy between 153Sm-EDTMP and 177Lu-EDTMP in terms of palliation of commonly encountered symptoms in cancer patients, functional status, and pain intensity as measured by Edmonton Symptom Assessment System (ESAS), Eastern Cooperative Oncology Group (ECOG) performance status, and numeric rating scale (NRS) respectively. This study was a double blind randomized clinical trial conducted in a setting of three university hospitals.

Materials and Methods: In a randomized double-blind clinical trial 50 patients will with documented painful bone metastases of blastic or mixed lytic-blastic nature were randomly allocated into two groups; group receiving 153Sm-EDTMP and group receiving 177Lu-EDTMP. Radiopharmaceuticals were given at a dose of 37.0 MBq / kg body weight in both groups. Scores on ESAS, ECOG performance status and NRS were recorded before the intervention and following the intervention at 2, 4, 6, and 12 weeks. Hematologic toxicity was evaluated by monitoring hematologic parameters at the baseline and at 1, 3, 6, and 8 weeks after the intervention.

Results: Fifty patients, 31 (62 %) females and 19 (38 %) males with the mean age of 66.08 ± 4.53 years were recruited. The baseline means and standard deviations for pain intensity as measured by the NRS were 8.4 ± 1.47 and 8.36 ± 1.43 in 153Sm-EDTMP- and 177Lu-EDTMP-treated subjects respectively. Patients of both groups showed significant alleviation of pain observed from the 2nd week (first follow up session) and continuing to the 12th week after treatment . No difference in response to the two radiopharmaceuticals were seen regarding their efficacy in pain alleviation (P < 1.0). Baseline “symptom distress scores” drawn from the ESAS-r in 153Sm-EDTMP- and 177Lu-EDTMP-treated groups were 5.5 ± 2.1 and 5.4 ± 2.1, respectively. The scores significantly improved in both groups with the most marked rate of improvement achieved within the first two weeks after treatment. The scores continued to improve until the 12th week of follow-up (P < 1.0, non-significant [ns]). Functional status as measured by ECOG performance status scores improved in both groups over the follow up period. Baseline scores on ECOG performance status in 153Sm-EDTMP- and 177Lu-EDTMP-treated groups were 2.5 ± 1.3 and 2.5 ± 1.3 (mean ± standard deviation). At 3 months post-treatment scores improved to 1.6 ± 0.6 and 1.6 ± 0.6 respectively (P < 1.0, n.s.).

Conclusions: 153Sm-EDTMP and 177Lu-EDTMP are safe and effective radiopharmaceuticals in palliation of cancer pain from multiple skeletal metastases of blastic and mixed lyticblastic nature.

Zusammenfassung

Einleitung: Knochenschmerzen von multifokalen blastischen oder gemischten lytisch-blastischen metastatischen Läsionen können mit Radiopharmazeutika mit hoher Affinität für solche Foki wirksam adressiert werden. 153Sm-EDTMP (Ethylendiamin-tetra[methylenphosphonsäure]) und 153Lu-EDTMP sind zwei dieser Radiopharmazeutika. Das Ziel der Studie war es, einen Vergleich der Wirksamkeit zwischen 153Sm-EDTMP und 177Lu-EDTMP im Hinblick auf die Linderung häufig auftretender Symptome bei Krebspatienten, den funktionellen Status und die Schmerzintensität, gemessen mit dem Edmonton Symptom Assessment System (ESAS), der Eastern Cooperative Oncology Group, durchzuführen (ECOG) Leistungsstatus bzw. numerische Bewertungsskala (NRS). Diese Studie war eine doppelblinde, randomisierte klinische Studie, die in drei Universitätskliniken durchgeführt wurde.

Material und Methoden: In einer randomisierten doppelblinden klinischen Studie wurden 50 Patienten mit dokumentierten schmerzhaften Knochenmetastasen blastischer oder gemischter lytisch-blastischer Art auf zwei Gruppen randomisert: eine Gruppe erhielt 153Sm-EDTMP und eine Gruppe 177Lu-EDTMP. Radiopharmazeutika wurden in einer Dosis von 37,0 MBq / kg Körpergewicht in beiden Gruppen verabreicht. Die Ergebnisse zu ESAS, ECOG-Leistungsstatus und NRS wurden vor der Intervention und nach der Intervention nach 2, 4, 6 und 12 Wochen aufgezeichnet. Die hämatologische Toxizität wurde durch Überwachung von hämatologischen Parametern zu Beginn und nach 1, 3, 6 und 8 Wochen nach dem Eingriff bewertet.

Ergebnisse: Fünfzig Patienten, 31 (62 %) Frauen und 19 (38 %) Männer mit einem Durchschnittsalter von 66,08 ± 4,53 Jahren wurden rekrutiert. Die Grundlinienmittelwerte und Standardabweichungen für die Schmerzintensität, gemessen durch die NRS, betrugen 8,4 ± 1,47 und 8,36 ± 1,43 in 153Sm-EDTMP-bzw. 177Lu-EDTMP-behandelten Patienten. Die Patienten beider Gruppen zeigten eine signifikante Schmerzlinderung, die von der 2. Woche (erste Nachuntersuchung) bis zur 12. Woche nach der Behandlung beobachtet wurde. Hinsichtlich ihrer Wirksamkeit bei der Schmerzlinderung wurde kein Unterschied in Bezug auf die zwei Radiopharmazeutika festgestellt (P < 1,0). Baseline „Symptom Distress Scores” aus dem ESAS-r in 153Sm-EDTMP- und 177Lu-EDTMP-behandelten Gruppen waren 5,5 ± 2,1 bzw. 5,4 ± 2,1. Die Werte verbesserten sich in beiden Gruppen signifikant, wobei innerhalb der ersten zwei Wochen nach der Behandlung die deutlichste Besserung erzielt wurde. Die Werte verbesserten sich bis zur 12. Woche der Nachuntersuchung (P < 1,0, nicht signifikant [n.s.]). Der funktionelle Status, gemessen anhand der ECOG-Leistungsstatuswerte, verbesserte sich in beiden Gruppen im Follow-up-Zeitraum. Die Baseline-Werte für den ECOG-Leistungsstatus in 153Sm-EDTMP- und 177Lu-EDTMP-behandelten Gruppen betrugen 2,5 ± 1,3 und 2,5 ± 1,3 (Mittelwert ± Standardabweichung). Nach 3 Monaten verbesserten sich die Ergebnisse auf 1,6 ± 0,6 bzw. 1,6 ± 0,6 (P < 1,0, n.s.).

Schlussfolgerungen: 153Sm-EDTMP und 177Lu-EDTMP sind sichere und wirksame Radiopharmaka zur Linderung von Tumorschmerzen bei multiplen skelettalen Metastasen blastischer und gemischter lytisch-blastischer Natur.

 
  • References

  • 1 Bodei L, Lam M, Chiesa C, Flux G, Brans B, Chiti A, Giammarile F. EANM procedure guideline for treatment of refractory metastatic bone pain. European journal of nuclear medicine and molecular imaging 2008; 35 (10) 1934.
  • 2 Tripathi M, Singhal T, Chandrasekhar N, Kumar P, Bal C, Jhulka PK, Bandopadhyaya G, Malhotra A. Samarium-153 ethylenediamine tetramethylene phosphonate therapy for bone pain palliation in skeletal metastases. Indian journal of cancer 2006; 43 (02) 86.
  • 3 Holmes RA. [153Sm] EDTMP: a potential therapy for bone cancer pain. In Seminars in nuclear medicine 1992; 22 (01) 41-45.
  • 4 Mercadante S. Malignant bone pain: pathophysiology and treatment. Pain 1997; 69 (1–2): 1-8.
  • 5 Borsò E, Boni G, Pastina I, Lorenzoni A, Cianci C, Federici F, Mazzarri S, Orlandini C, Francesca F, Selli C, Ricci S. Safety and antitumor efficacy of 153Sm-EDTMP and docetaxel administered sequentially to patients with metastatic castrationresistant prostate cancer. Nuclear medicine communication 2014; 35 (01) 88-94.
  • 6 Bouchet LG, Bolch WE, Goddu SM, Howell RW, Rao DV. Considerations in the selection of radiopharmaceuticals for palliation of bone pain from metastatic osseous lesions. The Journal of nuclear medicine 2000; 41 (04) 682.
  • 7 Dolezal J, Vizda J, Odrazka K. Prospective evaluation of samarium-153-EDTMP radionuclide treatment for bone metastases in patients with hormone-refractory prostate cancer. Urologia internationalis 2007; 78 (01) 50-57.
  • 8 Volkert WA, Hoffman TJ. Therapeutic radiopharmaceuticals. Chemical reviews 1999; 99 (09) 2269-2292.
  • 9 Krishnamurthy GT, Krishnamurthy S. Radionuclides for metastatic bone pain palliation: a need for rational re-evaluation in the new millennium. Journal of Nuclear Medicine 2000; 41 (04) 688-691.
  • 10 Sharma S, Singh B, Koul A, Mittal BR. Comparative Therapeutic Efficacy of 153Sm-EDTMP and 177Lu-EDTMP for Bone Pain Palliation in Patients with Skeletal Metastases: Patients’ Pain Score Analysis and Personalized Dosimetry. Frontiers in medicine 2017; 04: 46.
  • 11 Das T, Chakraborty S, Sarma HD, Tandon P, Banerjee S, Venkatesh M, Pillai MR. 170Tm-EDTMP: a potential cost-effective alternative to 89SrCl2 for bone pain palliation. Nuclear medicine and biology 2009; 36 (05) 561-568.
  • 12 Chopra A. [170Tm]-Labeled ethylenediamine tetramethylene phosphonic acid..
  • 13 Thapa P, Nikam D, Das T, Sonawane G, Agarwal JP, Basu S. Clinical Efficacy and Safety Comparison of 177Lu-EDTMP with 153Sm-EDTMP on an Equidose Basis in Patients with Painful Skeletal Metastases. Journal of nuclear medicine: official publication, Society of Nuclear Medicine 2015; 56 (10) 1513-1519.
  • 14 Shinto AS, Shibu D, Kamaleshwaran KK, Das T, Chakraborty S, Banerjee S, Thirumalaisamy P, Das P, Veersekar G. 177Lu-EDTMP for treatment of bone pain in patients with disseminated skeletal metastases. Journal of nuclear medicine technology 2014; 42 (01) 55-61.
  • 15 Correa-González L, de Murphy CA, Pichardo-Romero P, Pedraza-Lüpez M, Moreno-Garcí C, Correa-Hernández L. 153Sm-EDTMP for pain relief of bone metastases from prostate and breast cancer and other malignancies. Archives of medical research 2014; 45 (04) 301-308.
  • 16 Anderson P, Nuñez R. Samarium lexidronam (153Sm-EDTMP): skeletal radiation for osteoblastic bone metastases and osteosarcoma. Expert review of anticancer therapy 2007; 07 (11) 1517-1527.
  • 17 Alavi M, Omidvari S, Mehdizadeh A, Jalilian AR, Bahrami-Samani A. Metastatic bone pain palliation using 177Lu-ethylenediaminetetramethylene phosphonic acid. World journal of nuclear medicine 2015; 14 (02) 109.
  • 18 Wilky BA, Loeb DM. Beyond Palliation: Therapeutic Applications of 153Samarium-EDTMP. Clinical & experimental pharmacology. 2013 03. (3).
  • 19 Yuan J, Liu C, Liu X, Wang Y, Kuai D, Zhang G, Zaknun JJ. Efficacy and safety of 177Lu-EDTMP in bone metastatic pain palliation in breast cancer and hormone refractory prostate cancer: a phase II study. Clinical nuclear medicine 2013; 38 (02) 88-92.
  • 20 Farhanghi M, Holmes RA, Volkert WA, Logan KW, Singh A. Samarium-153-EDTMP: pharmacokinetic, toxicity and pain response using an escalating dose schedule in treatment of metastatic bone cancer. Journal of Nuclear Medicine 1992; 33 (08) 1451-1458.
  • 21 Mertens WC, Filipczak LA, Ben-Josef E, Davis LP, Porter AT. Systemic bone-iseeking radionuclides for palliation of painful osseous metastases: Current concepts. CA: a cancer journal for clinicians 1998; 48 (06) 361-374.
  • 22 Bryan JN, Bommarito D, Kim DY, Berent LM, Bryan ME, Lattimer JC, Henry CJ, Engelbrecht H, Ketring A, Cutler C. Comparison of systemic toxicities of 177Lu-DOTMP and 153Sm-EDTMP administered intravenously at equivalent skeletal doses to normal dogs. Journal of nuclear medicine technolog 2009; 37 (01) 45-52.
  • 23 Chakraborty S, Das T, Banerjee S, Balogh L, Chaudhari PR, Sarma HD, Polyák A, Máthé D, Venkatesh M, Janoki G, Pillai MR. 177LuEDTMP: a viable bone pain palliative in skeletal metastasis. Cancer biotherapy & radiopharmaceuticals 2008; 23 (02) 202-213.
  • 24 Ranjbar H, Bahrami-Samani A, Beiki D, ShirvaniArani S, Ghannadi-Maragheh M. Evaluation of 153Sm/177Lu-EDTMP mixture in wild-type rodents as a novel combined palliative treatment of bone pain agent. Journal of Radioanalytical and Nuclear Chemistry 2015; 303 (01) 71-79.
  • 25 Kolesnikov-Gauthier H, Lemoine N, Tresch-Bruneel E, Olivier A, Oudoux A, Penel N. Efficacy and safety of 153 Sm-EDTMP as treatment of painful bone metastasis: a large single-center study. Supportive Care in Cancer 2018; 26 (03) 751-758.