# 116 Radiopharmaceuticals for Painful Osseous Metastases

FAST FACTS AND CONCEPTS #116

Author(s): Gary M Reisfield MD and George R Wilson MD

Introduction   This Fast Fact reviews bone-seeking radiopharmaceuticals (radionuclides), which occupy a valuable niche in the palliation of painful bone metastases (see Fast Facts #66 and 67 for a general discussion of palliative radiation).

Isotopes and Physiology The three isotopes available in this country – 89Sr (strontium-89), 153Sm (samarium-153), and 32P (phosphorus-32) – work by binding with high affinity to hydroxyapatite in regions of rapid bone turnover near osteoblastic metastases, delivering therapeutic doses of localized beta radiation, with a tissue penetration measured in millimeters. The precise mechanism of analgesia is unknown but is probably not dependent solely on cell kill. Rather, analgesia may also be a function of inhibition of lymphocyte-associated cytokines or alterations in osteoclast and/or osteoblast activity.

Benefits   Analgesia may begin within 3-7 days, but more typically begins within one to two weeks after administration. Analgesia will last from two to six months; treatment may be repeated. Symptom improvement is noted in 60-80% of patients, with complete analgesia in 20-30% of responders. Radiopharmaceuticals may delay onset of pain in pre-existing, clinically silent metastases.

Procedure   The radiopharmaceutical is delivered in the outpatient setting by a single IV injection or orally (32P only). Administration requires no special monitoring.

Patient selection   Patients with multiple painful bone metastases, demonstrated by bone scan and/or plain X-ray, corresponding to site(s) of pain and an expected survival of >12 weeks are appropriate for radiopharmaceutical therapy. Evidence supporting efficacy in prostate and breast cancer is substantial; data for other tumor types are limited.

Contraindications

  • Preexisting myelosuppression (e.g. WBC <3.0K and Platelets <60-100K).
  • Oncological urgencies/emergencies in which radiopharmaceuticals will be of no benefit (e.g. actual or impending spinal cord compression or pathologic fracture).
  • Renal insufficiency (relative contraindication).
  • Evidence of disseminated intravascular coagulation (relative contraindication).
  • Pregnancy

Adverse effects

  • Marrow suppression: Reversible, moderate neutropenia and thrombocytopenia – manifested by approximately 30-70% drop in leukocyte and platelet counts – is a predictable side effect. Depending on the specific agent this begins two to four weeks following administration, with a nadir between weeks four to six. Bone marrow recovery occurs by weeks eight to twelve.
  • Pain flare: Increasing pain occurs in 10-20% of patients, usually within the first week of administration. It is transient and may be predictive of a good therapeutic response.

Approximate retail costs (Note: dosing is calculated based on patient weight.)

  • Strontium-89 chloride injection: $3,097 / 5 mCi.
  • Samarium-153 lexidronam injection $2,770 / 150 mCi.
  • Sodium phosphate P-32 solution: $500 / 5 mCi.

Comparative Data There is little data comparing the three agents. However, the International Atomic Energy Agency sponsored a randomized, single-blind study comparing a single doses of oral 32P (12 mCi) and intravenous 89Sr (4 mCi). Patients were well-matched in terms of tumor type, degree of osseous involvement, and pretreatment pain scores. Partial (>50%) and complete (100%) analgesia responses were as follows: 89Sr: 7/15 and 8/15 patients, respectively; 32P: 7/16 and 7/16 patients, respectively. There were no significant differences in onset/duration/degree of analgesia or functional improvement. Hematologic toxicity was comparable save except that the 32P group had more thrombocytopenia.

References

  1. Hellman RS, Krasnow AZ. Radionuclide therapy for palliative of pain due to osteoblastic metastases. J Pall Med. 1998; 1:277-283.
  2. Silberstein EB. Painful osteoblastic metastases: the role of nuclear medicine. Oncology. 2001; 15(2):157-163.
  3. Lewington VJ. A practical guide to targeted therapy for bone pain palliation. Nucl Med Commun. 2002; 23(9):833-836.
  4. Mertens WC, Filipczak LA, Ben-Josef E, Davis LP, Porter AT. Systemic bone-seeking radionuclides for palliation of painful osseous metastases: current concepts. CA Cancer J Clin.1998; 48(6):361-374.
  5. Nair N. Relative efficacy of 32P and 89Sr in palliation in skeletal metastases. J Nucl Med. 1999; 40(2):256-261.


Fast Facts and Concepts are edited by Drew A Rosielle MD, Palliative Care Center, Medical College of Wisconsin. For more information write to: drosiell@mcw.edu. More information, as well as the complete set of Fast Facts, are available at EPERC: www.eperc.mcw.edu.

Version History: This Fast Fact was originally edited by David E Weissman MD and published in June 2004. Re-copy-edited in April 2009.

Copyright/Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Reisfield GM, Wilson GR. Radiopharmaceuticals for Painful Osseous Metastases. Fast Facts and Concepts. June 2004; 116. Available at: http://www.eperc.mcw.edu/fastfact/ff_116.htm.

Disclaimer: Fast Facts and Concepts provide educational information. This information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Facts cite the use of a product in a dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.

ACGME Competencies: Medical Knowledge, Patient Care

Keyword(s): Pain – Non-Opioids