The estimated absorbed radiation doses to an average 70 kg adult patient from an i.v.
injection of QUADRAMET® are shown in Table 7.
The dosimetry estimates were based on clinical biodistribution studies using methods developed for radiation dose calculations by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine.Radiation exposure is based on a urinary voiding interval of 4.8 hours.
Radiation dose estimates for bone and marrow assume that radioactivity is deposited on bone surfaces, as noted in autoradiograms of biopsy bone samples in 7 patients who received QUADRAMET®.
Although electron emissions from 153Sm are abundant, with energies up to 810 keV, rapid blood clearance of QUADRAMET® and low energy and abundant photon emissions generally result in low radiation doses to those parts of the body where the complex does not localize.When blastic osseous lesions are present, significantly enhanced localization of the radiopharmaceutical will occur, with correspondingly higher doses to the lesions compared with normal bones and other organs.(See Clinical Pharmacology, Skeletal Uptake and Pharmacodynamics Sections).TABLE 7 RADIATION ABSORBED DOSES 70 kg ADULT Target Organ Rad/mCimGy/MBq Bone Surfaces 25.0 6.76 Red Marrow 5.70 1.54 Urinary Bladder Wall 3.60 0.097 Kidneys 0.065 0.018 Whole Body 0.040 0.011 Lower large intestine 0.037 0.010 Ovaries 0.032 0.0086 Muscle 0.028 0.0076 Small Intestine 0.023 0.0062 Upper Large Intestine 0.020 0.0054 Testes 0.020 0.0054 Liver 0.019 0.0051 Spleen 0.018 0.0049 Stomach 0.015 0.0041
QUADRAMET® causes bone marrow suppression.
In clinical trials, white blood cell counts and platelet counts decreased to a nadir of approximately 40% to 50% of baseline in 123 (95%) of patients within 3 to 5 weeks after QUADRAMET®, and tended to return to pretreatment levels by 8 weeks.
The grade of marrow toxicity is shown in Table 5 below.Table 5: NUMBER AND PERCENT OF PATIENTS WHO EXPERIENCED MARROW TOXICITY IN CLINICAL TRIALS OF QUADRAMET® HemoglobinLeucocytesPlatelets Toxicity Grade* Placebo N=85 1.0 mCi/kg N=185 Placebo N=85 1.0 mCi/kg N=184 Placebo N=85 1.0 mCi/kg N=185 0-2 78 (92%) 162 (88%) 85 (100%) 169 (92%) 85 (100%) 173 (94%) 3 6 (7%) 20 (11%) 0 (0%) 15 (8%) 0 (0%) 10 (5%) 4 1 (1%) 3 (2%) 0 (0%) 0 (0%) 0 (0%) 2 (1%) * Toxicity Grade based upon National Cancer Institute Criteria; normal levels are Hemoglobin ?10g/dL, Leucocyte ?4.0 x 103µL, and Platelets ?150,000/µL.Before QUADRAMET® is administered, consideration should be given to the patient’s current clinical and hematologic status and bone marrow response history to treatment with myelotoxic agents.
Metastatic prostate and other cancers can be associated with disseminated intravascular coagulation (DIC); caution should be exercised in treating cancer patients whose platelet counts are falling or who have other clinical or laboratory findings suggesting DIC.
Because of the unknown potential for additive effects on bone marrow, QUADRAMET® should not be given concurrently with chemotherapy or external beam radiation therapy unless the clinical benefits outweigh the risks.
Use of QUADRAMET® in patients with evidence of compromised bone marrow reserve from previous therapy or disease involvement is not recommended unless the potential benefits of the treatment outweigh the risks.Blood counts should be monitored weekly for at least 8 weeks, or until recovery of adequate bone marrow function.