This radiopharmaceutical was the most widely employed agent for the treatment of bone pain from osseous metastases between 1950 and approximately 1980. It is usually administered intravenously, but there are studies showing equal efficacy with oral administration, where absorption varies between 40% and 80%. Oral P-32, which is much less expensive than any of the radiotracers to be discussed (and therefore suitable for developing countries) was compared in 1999 with intravenous Sr-89 in an study sponsored by the International Atomic Energy Agency (IAEA). There was no significant difference found in response rates from P-32 or Sr-89 treatment; both were about 90% efficacious. In the early years of P-32 utilization, it was employed after a week of androgen therapy in the belief that tumor and bone uptake would be stimulated. However, the data on which this supposition was made were flawed. Androgen administration can lead to severe side effects, such as spinal cord compression in the presence of bone metastases. Clinical results without administered andro-gens were as good as with this hormone preparation (or with the use of parathyroid hormone). P-32 not only distributes throughout bone hydroxyapatite as a substitute for the stable phosphate, but it also is incorporated into nucleic acids, compounds with high-energy phosphate bonds such as adenosine triphospate (ATP) and creatine phosphate, and in kinases signaling receptor activation. In fact, P-32 was first used for its myelosuppressive properties by John Lawrence in 1939, when studies on P-32 treatment of myeloproliferative and lymphoproli-ferative diseases began. Its use for reduction of bone pain started in about 1950, and the fears some have had for the dangers of P-32 myelosuppression were never realized. In fact, only one death and one intracerebral hemorrhage from P-32-induced myelosuppression have been reported. Response rates for pain reduction have ranged between 60% and 90%, with earlier studies especially lacking in rigorous methodology to measure the factors surrounding pain reduction. In the recent IAEA-sponsored study noted before, P-32 caused grade 2 marrow toxicity (platelets 50,000-74,999/ul; leukocytes 2000-2999/ul) in a minority of patients, with no clinical sequelae. A comparative study of P-32 with hemibody radiation detected equivalent therapeutic responses, although hemibody radiation yielded faster clinical responses and more toxicity. Responses to P-32 in the form of pain palliation are generally seen between days 5 and 14 after injection, a time range rather similar to all the other radiopharmaceuticals under discussion. Metastatic breast and prostate carcinoma do not differ in their response rates.
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