Professional Drug Information > Strontium Chloride Sr 89

Strontium Chloride SR 89 (Systemic)

VA CLASSIFICATION
Primary: AN600

Commonly used brand name(s): Metastron.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antineoplastic—

Indications

Accepted

Bone lesions, metastatic (treatment)—Strontium chloride Sr 89 ^{37} is indicated in the palliative treatment of bone pain in selected patients with multiple areas of skeletal metastases from carcinomas of the prostate, breast, and possibly, from other carcinomas. ^{{01} {06} {07} {09} {10} {11} {13} {15} {17} {23} {24} {25} {26} {27} {28} {29} {30} {31} {34}}


Physical Properties

Nuclear data ^{{01} {32} {35}}

Radionuclide (half-life)	Mode of decay	Maximum energy (MeV)	Mean number of emissions/ disintegration
Sr 89 (50.5 days)	Beta	1.463	1

Pharmacology/Pharmacokinetics

Mechanism of action/Effect:

Antineoplastic—Metastatic bone lesions: Strontium chloride Sr 89, a calcium analog, follows the same biochemical pathways as calcium does in vivo and concentrates in areas of increased osteogenesis (i.e., increased mineral turnover), not in marrow cells. Thus, reactive osteoid being formed at sites of primary bone tumors and metastases accumulate strontium to a much higher level than does surrounding normal bone. The retained strontium can deliver a radiation dose sufficiently large to produce a palliative effect. Due to the short range of the beta particles, the cells close to regions containing strontium will be preferentially irradiated. ^{{01} {05} {08} {13} {16} {17} {28} {32} {33} {34} {35}}

Distribution:

Distribution similar to calcium analogs with fairly rapid clearance from the blood and selective localization in bone hydroxyapatite. ^{{01} {02} {08} {16} {34}}

Onset of action:

Pain relief may begin between 7 and 21 days following administration of strontium chloride Sr 89, with maximum relief by 6 weeks. ^{{01} {16} {28} {32} {34}}

Duration of action:

Duration of pain relief averages 6 months, with a range of 4 to 12 months. ^{{01} {16} {32}}

Radiation dosimetry:
^{02}{08}

Estimated absorbed radiation dose*†
Organ	mGy/MBq	rad/mCi
Bone surfaces	17.0	62.96
Red marrow	11.0	40.74
Large intestine wall (lower)	4.7	17.41
Large intestine wall (upper)	1.8	6.67
Bladder wall	1.3	4.81
Breast	0.96	3.55
Adrenals	0.78	2.89
Stomach wall	0.78	2.89
Kidneys	0.78	2.89
Liver	0.78	2.89
Lungs	0.78	2.89
Ovaries	0.78	2.89
Pancreas	0.78	2.89
Spleen	0.78	2.89
Testes	0.78	2.89
Thyroid	0.78	2.89
Uterus	0.78	2.89
Small intestine	0.023	0.085
Other tissue	0.78	2.89
Effective dose: 2.9 mSv/MBq (10.73 rem/mCi)

^* For adults; intravenous injection. Data based on the International Commission on Radiological Protection (ICRP) Publication 53—Radiation dose to patients from radiopharmaceuticals. ^{02}
† The absorbed dose to individual metastatic sites ranges from 60 to 610 mGy/MBq (220 to 2260 rad/mCi) with a mean dose of 230 mGy/MBq (850 rad/mCi). ^{{35} {36}}

Elimination:
    Renal, by glomerular filtration (two-thirds of excreted activity), and fecal (one-third) in patients with bone metastases. Renal excretion is greatest in the first 2 days after treatment. ^{{01} {02}} Strontium 89 is lost from normal bone with an initial biological half-life of 14 days, but retained much longer in metastatic bone lesions. ^{32} Patients with extensive metastases may retain 50 to 100% of the administered activity in bone and may excrete less than do persons without bone lesions. Whole body retention of strontium varies according to individual urinary plasma clearance and metastatic load in the skeleton; between 12 and 90% of the administered activity is retained 3 months after administration of strontium chloride Sr 89. ^{{01} {16} {32} {34} {35}}


Precautions to Consider

Carcinogenicity/Mutagenicity

Thirty-three out of 40 rats receiving 10 consecutive monthly doses of either 250 or 350 microcuries per kg of body weight of strontium chloride Sr 89 developed malignant bone tumors after a latency period of approximately 9 months. ^{01}

Pregnancy/Reproduction

Pregnancy—
Adequate and well-controlled studies with strontium chloride Sr 89 have not been done in humans. Radiopharmaceuticals are generally not recommended for therapeutic use during pregnancy because of the risk to the fetus from radiation exposure. Strontium chloride Sr 89 would be expected to cause adverse effects, such as bone marrow toxicity, in the fetus. ^{{01} {34}}

To avoid the possibility of fetal exposure to radiation, in those circumstances in which the patient's pregnancy status is uncertain, a pregnancy test will help to prevent inadvertent administration of this preparation during pregnancy. ^{02}

Studies have not been done in animals.

FDA Pregnancy Category D. ^{01}

Breast-feeding

Strontium chloride Sr 89 acts as a calcium analog and is expected to be distributed into breast milk. Because of the potential risk to the infant from radiation exposure, complete cessation of nursing is recommended after strontium chloride Sr 89 has been administered. ^{{01} {34} {35}}

Pediatrics

There have been no specific studies evaluating the safety and efficacy of strontium chloride Sr 89 in children. ^{{03} {34}}


Geriatrics


Appropriate studies on the relationship of age to the effects of strontium chloride Sr 89 have not been performed in the geriatric population. However, no geriatrics-specific problems have been documented to date. ^{{19} {25}}

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

» Blood-dyscrasia–causing medications (See Appendix II )    (leukopenic and/or thrombocytopenic effects of strontium chloride Sr 89 may be increased ^{34})


» Calcium-containing medications    (saturation of bone-binding sites by calcium may cause decreased bone uptake of strontium chloride Sr 89; calcium-containing medications should be discontinued at least 2 weeks before therapy with strontium chloride Sr 89; calcium-containing medication may be resumed approximately 2 weeks after strontium chloride Sr 89 therapy ^{{16} {32} {34}})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Alkaline phosphatase    (serum values may be decreased, reflecting tumoricidal effect ^{{15} {25} {34}})


Serum tumor markers, such as prostatic specific antigen (PSA) and prostate acid phosphatase (PAP)    (concentration may be decreased, reflecting tumoricidal effect ^{{24} {25} {34}})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problem exists:
» Bone marrow depression, with platelet count less than 60,000 per microliter and white cell count less than 2,400 per microliter, especially with previous or concomitant chemotherapy or radiotherapy administration^{{01}{05}{32}{34}{35}}    (increased risk of toxicity due to compromised bone marrow)


Risk-benefit must be considered when the following medical problems exist
Sensitivity to the radiopharmaceutical preparation
Urinary incontinence    (increased risk of radiation contamination of environment; therefore, urinary catheterization is recommended ^{{01} {32} {34}})


Very short life-expectancy    (use not warranted since onset of pain relief may not occur for 10 to 20 days ^{{01} {34}})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Blood studies, including leukocyte and platelet counts    (recommended prior to therapy and at least once every other week for 3 to 4 months after therapy ^{{01} {16} {19} {34}})






Side/Adverse Effects

Note: A single case of fatal septicemia following leukopenia has been reported during clinical trials. ^{01}


Those indicating need for medical attention
Incidence rare
    
Bone marrow depression leading to thrombocytopenia (unusual bleeding or bruising; black, tarry stools; blood in urine or stools; pinpoint red spots on skin), and leukopenia (cough or hoarseness; fever or chills; lower back or side pain; painful or difficult urination)^{{01}{11}{16}{19}{22}{26}{31}{32}{34}}
Note: On the average, platelet concentrations may fall by 30% of pretreatment levels (i.e., fall to 70% of baseline); however, this effect is generally reversible, and the majority of patients maintain platelet counts that are within normal limits. The nadir of platelet depression occurs in most patients about 6 weeks after administration of strontium chloride Sr 89. ^{{01} {11} {16} {26} {28} {32} {34}}
Bone marrow toxicity may be difficult to evaluate because marrow suppression is common in patients with prostate cancer and extensive bone metastases. ^{{16} {19}}





Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Flare reaction (increase in bone pain, transient)
    
flushing —with rapid administration^{01}{32}{35}





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Strontium Chloride Sr 89 (Therapeutic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Description of use
Action in the body: Active incorporation of strontium 89 into bone mineral, especially in areas of tumor involvement; localized radiation exposure to these sites provides reduction in bone pain

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to the radiopharmaceutical preparation

Pregnancy—Use not recommended; risk to fetus from radiation exposure





Breast-feeding—May be distributed into breast milk; cessation of nursing is recommended because of risk to infant from radiation exposure
Other medications, especially blood dyscrasia–causing and calcium-containing

Proper use of this medication
Special preparatory instructions may apply; patient should inquire in advance

Notifying physician prior to administration if having an incontinence problem; catheterization may be required to prevent radiation contamination

Precautions after using this medication
» Importance of close monitoring by the physician

To prevent radiation contamination of other persons or environment—For the first week
» Using a normal toilet instead of a urinal
» Double-flushing toilet
» Wiping any spilled urine with a tissue and flushing it away
» Washing hands after using or cleaning toilet
» Immediately laundering clothes and linens soiled with urine or blood; washing them separately from other clothes
» Washing away any spilled blood» Caution if significant bone marrow depression occurs

Abnormally low white blood cell counts


• Avoiding exposure to persons with bacterial infections, especially during periods of low blood counts; checking with physician immediately if fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination occurs


• Caution in use of regular toothbrush, dental floss, or toothpick; physician, dentist, or nurse may suggest alternatives; checking with physician before having dental work done; not touching eyes or inside of nose unless hands washed immediately before


Abnormally low platelet counts


• Using caution to avoid accidental cuts with use of sharp objects such as safety razor or fingernail or toenail cutters


• Avoiding contact sports or other situations where bruising or injury could occur



Side/adverse effects
Signs of potential side effects, especially bone marrow depression


General Dosing Information
Radiopharmaceuticals are to be administered only by or under the supervision of physicians who have had extensive training in the safe use and handling of radioactive materials and who are authorized by the Nuclear Regulatory Commission (NRC) or the appropriate Agreement State agency, if required, or, outside the U.S., the appropriate authority. ^{03}

The presence of bone metastases must be confirmed (e.g., by skeletal imaging with a technetium Tc 99m–labeled phosphate or phosphonate radiopharmaceutical) prior to therapy with strontium chloride Sr 89. ^{{32} {34}}

Treatment may be repeated at intervals of 3 months or more if pain recurs. However, previous hematologic response, current platelet level, and other signs of bone marrow depression should be carefully evaluated before therapy with strontium chloride Sr 89 is repeated. ^{{01} {16} {19} {32} {34}}

Safety considerations for handling this medication
Improper handling of this radiopharmaceutical may cause radioactive contamination. Guidelines for handling radioactive material have been prepared by scientific, professional, state, federal, and international bodies and are available to the specially qualified and authorized users who have access to radiopharmaceuticals ^{34}


Parenteral Dosage Forms

STRONTIUM CHLORIDE Sr 89 INJECTION USP

Usual adult administered activity
Antineoplastic
Metastatic bone lesions: Intravenous, 1.5 to 2.2 megabecquerels (40 to 60 microcuries) per kg of body weight, or a total administered activity of 148 megabecquerels (4 millicuries) given slowly (one to two minutes) as a single dose. ^{{01} {05} {16} {21} {28} {29} {31} {34}}

Note: Repeated administration at intervals of less than ninety days is generally not recommended. ^{01}



Usual pediatric administered activity
Children up to 18 years of age: Minimum dosage has not been established. ^{01}

Usual geriatric administered activity
See Usual adult administered activity .

Strength(s) usually available
U.S.—


148 megabecquerels (4 millicuries) in 4-mL volume per 10-mL vial, containing 10.9 to 22.6 mg of strontium chloride per mL, and a specific activity of 2.96 to 6.17 megabecquerels (80 to 167 microcuries) per mg of strontium, at time of calibration (Rx) [Metastron]

Canada—


150 megabecquerels (4.05 millicuries) in 4-mL volume per 10-mL vial, containing 13.4 to 20.1 mg of strontium chloride per mL, and a specific activity of 3.33 to 5 megabecquerels (90 to 135 microcuries) per mg of strontium, at time of calibration (Rx) [Metastron]

Packaging and storage:
Store between 15 and 25 °C (59 and 77 °F), unless otherwise specified by manufacturer. Protect from freezing. ^{{01} {32}}

Stability:
Product should not be used beyond 4 weeks after calibration. ^{{01} {32}}

Note: Caution—Radioactive material.

Revised: 05/18/1995

References

1. Metastron package insert (Amersham—US), Rev 7/93.
   

2. Task group of Committee 2 of the International Commission on Radiological Protection: ICRP Publication 53—Radiation dose to patients from radiopharmaceuticals. New York: Pergamon Press, 1988: 170.
   

3. Standard statement recommended by the USP Radiopharmaceuticals Advisory Panel during 5/91 meeting.
   

4. Personal communication, Nicholas Borys, MD, Medical Affairs Director, Medi-Physics, 9/24/93.
   

5. Ackery D, Yardley J. Radionuclide-targeted therapy for the mangement of metastatic bone pain. Semin Oncol 1993; 20(3 Suppl 2): 27-31.
   

6. Bagshaw MA, Kaplan ID, Valdagni R, et al. Radiation treatment of prostate bone metastases and the biological considerations. Adv Exp Med Biol 1992; 324: 255-68.
   

7. Kovner F, Ron IG, Levita M, et al. Strontium-89 therapy in a patient with carcinoma of unknown origin and incurable pain from metastases. J Pain Symptom Manage 1993; 8(1): 47-51.
   

8. Breen SL, Powe JE, Porter AT. Dose estimation in strontium-89 radiotherapy of metastatic prostatic carcinoma. J Nucl Med 1992; 33: 1316-23.
   

9. Buchali K, Correns HJ, Schurer M, et al. Results of a double blind study of strontium 89 therapy of skeletal metastases of prostatic carcinoma. Eur J Nucl Med 1988; 14(7-8): 349-51.
   

10. Dearnaley DP, Bayly RJ, A'Hern RP, et al. Palliation of bone metastases in prostate cancer. Hemibody irradiation of strontium 89? Clin Oncol (R Coll Radiol) 1992; 4(2): 101-7.
    

11. Fossa SD, Paus E, Lochoff M, et al. Strontium 89 in bone metastases from hormone resistant prostate cancer: palliation effect and biochemical changes. Br J Cancer 1992; 66(1): 177-80.
    

12. Frassica DA, Gunderson LL. Principles of radiation therapy in the treatment of bone metastases. Orthopedica 1992; 15(5): 579-81.
    

13. Hansen DV, Holmes ER, Catton G, et al. Strontium 89 therapy for painful osseous metastatic prostate and breast cancer. Am Fam Physician 1993; 47(8): 1795-800.
    

14. Holmes RA. Radiopharmaceuticals in clinical trials. Semin Oncol 1993; 20(3 Suppl 2): 22-6.
    

15. Kloiber R, Molnar CP, Barnes M. Sr 89 therapy for metastatic bone disease: scintigraphic and radiographic follow-up. Radiology 1987; 163(3): 719-23.
    

16. Laing AH, Ackery DM, Bayly RJ, et al. Strontium 89 chloride for pain palliation in prostatic skeletal malignancy. Br J Radiol 1991; 64(765): 816-22.
    

17. Lewington VJ, McEwan AJ, Ackery DM, et al. A prospective, randomised double-blind crossover study to examine the efficacy of strontium 89 in pain palliation in patients with advanced prostate cancer metastatic to bone. Eur J Cancer 1991; 27(8): 954-8.
    

18. Lewington VJ. Targeted radionuclide therapy for bone metastases. Eur J Nucl Med 1993; 20(1): 66-74.
    

19. McEwan AJB, Porter AT, Venner PM, et al. An evaluation of the safety and efficacy of treatment with strontium-89 in patients who have previously received wide field radiotherapy. Antibody, Immunoconjugates, and Radiopharmaceuticals 1990; 3(2): 91-8.
    

20. Mertens WC, Porter AT, Reid RH, et al. Strontium 89 and low-dose infusion cisplatin for patients with hormone refractory prostate carcinoma metastatic to bone: a preliminary report. J Nucl Med 1992; 33(8): 1437-43.
    

21. Mertens WC, Stitt L, Porter AT. Strontium 89 therapy and relief of pain in patients with prostatic carcinoma metastatic to bone: a dose response relationship? Am J Clin Oncol 1993; 16(3): 238-42.
    

22. Montebello JF, Hartson-Eaton M. The palliation of osseous metastasis with P 32 or Sr 89 compared with external beam and hemibody irradiation: a historical perspective. Cancer Invest 1989; 7(2): 139-60.
    

23. Perez CA, Cosmatos D, Garcia DM, et al. Irradiation in relapsing carcinoma of the prostate. Cancer 1993; 71(Suppl 3): 1110-22.
    

24. Porter AT, McEwan AJ. Strontium 89 as an adjuvant to external beam radiation improves pain relief and delays disease progression in advanced prostate cancer: results of a randomized controlled trial. Semin Oncol 1993; 20(3 Suppl 2): 38-43.
    

25. Porter AT, McEwan AJ, Powe JE, et al. Results of a randomized phase-III trial to evaluate the efficacy of strontium 89 adjuvant to local field external beam irradiation in the management of endocrine resistant metastatic prostate cancer. Int J Radiat Oncol Biol Phys 1993; 25(5): 805-13.
    

26. Robinson RG, Preston DF, Baxter KG, et al. Clinical experience with strontium 89 in prostatic and breast cancer patients. Semin Oncol 1993; 20(3 Suppl 2): 44-8.
    

27. Robinson RG, Preston DF, Spicer JA, et al. Radionuclide therapy of intractable bone pain: emphasis on strontium 89. Semin Nucl Med 1992; 22(1): 28-32.
    

28. Robinson RG, Blake GM, Preston DF, et al. Strontium 89: treatment results and kinetics in patients with painful metastatic prostate and breast cancer in bone. Radiographics 1989; 9(2): 271-81.
    

29. Robinson RG, Spicer JA, Preston DF, et al. Treatment of metastatic bone pain with strontium 89. Int J Rad Appl Instrum 1987; 14(3): 219-22.
    

30. Silberstein EB, Williams C. Strontium 89 therapy for the pain of osseous metastases. J Nucl Med 1985; 26(4): 345-8.
    

31. Tennvall J, Darte L, Lundgren R, et al. Palliation of multiple bone metastases from prostatic carcinoma with strontium 89. Acta Oncol 1988; 27(4): 365-9.
    

32. Metastron package insert (Amersham—Canada), Rev 12/89.
    

33. Blake GM, Zivanovic MA, McEwan AJ, et al. Sr-89 therapy: strontium kinetics in disseminated carcinoma of the prostate. Eur J Nucl Med 1986; 12: 447-54.
    

34. Reviewers' responses to monograph revision of 09/20/93.
    

35. Reviewers' responses to monograph revision of 01/17/94.
    

36. Blake GM, Zivanovic MA, Blaquiere RM, et al. Strontium-89 therapy: measurement of absorbed dose to skeletal metastases. J Nucl Med 1988; 29(4): 549-57.
    

37. The United States Pharmacopeia. The national formulary. USP 23rd revision (January 1, 1995). NF 18th ed (January 1, 1995). Rockville, MD: The United States Pharmacopeial Convention, Inc., 1995 (Second supplement, 1995): 2677.