Fast Fact and Concept #116: Radiopharmaceuticals for painful osseous metastases

Author(s): Reisfield Gary M; Wilson, George R

Bone-seeking radiopharmaceuticals (radionuclides) occupy a valuable niche in the palliation of painful bone metastases. 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. Analgesia may begin within 3-7days, 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:
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. Evidence supporting efficacy in prostate and breast cancer is substantial; data for other tumor types is limited.

Contraindications:

1. Preexisting myelosuppression, (WBC < 3.0 K and PLT < 60-100 K.)
2. Oncological urgencies/emergencies (in which radiopharmaceuticals will be of no benefit): (e.g. Actual or impending spinal cord compression or pathologic fracture)
3. Renal insufficiency (relative contraindication).
4. Evidence of disseminated intravascular coagulation (relative contraindication).
5. Pregnancy

Adverse effects:

1. 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.
2. 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.

Costs: (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

Note: 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 32P group had more thrombocytopenia.

References:

1. Hellman RS and 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 were edited by David Weissman MD, Palliative Care Center, Medical College of Wisconsin until January 2007.  For comments/questions write to the current editor, Drew Rosielle MD: drosiell@mcw.edu. The complete set of Fast Facts is available at EPERC: www.eperc.mcw.edu

Copyright/Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Citation for referencing: Reisfeld GM and Wilson GR. Fast Facts and Concepts #116: Radiopharmaceuticals for painful osseous metastases. June 2004. End-of-Life/Palliative Education Resource Center www.eperc.mcw.edu.

Disclaimer: Fast Facts provide educational information, this information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Fact information cites the use of a product in 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.

Creation Date: 6/2004

Purpose: Instructional Aid, Self-Study Guide, Teaching

Audience(s)

ACGME Competencies: Medical Knowledge, Patient Care

Keyword(s): Pain>non-opioids; cancer

Specific Disease and Organ System Category(s): Cancer