MedLibrary.org

Prescription Medications

Quadramet (Page 2 of 4)

Drug/Drug Interaction

Drug-drug interaction studies have not been studied.

Pharmacodynamics

The beta particle of 153 Sm-EDTMP travels an average of 3.1 mm in soft tissue and 1.7 mm in bone. In clinical trials of 78 patients with metastatic bone lesions who had 13 specific bone scan sites evaluated, the presence or absence of 153 Sm-EDTMP uptake is similar to the presence or absence of 99m Tc diphosphonate uptake (range 67 to 96% agreement depending upon the blinded reader and the site of the body). Whether the amount of 153 Sm-EDTMP uptake varies with the size of the lesion or to the presence of osteolytic components has not been studied. The clinical benefit of Sm-153-EDTMP in patients with osteolytic lesions is not known. The relationship of different tumor cell types to clinical response has not been studied.

CLINICAL TRIALS

Overall QUADRAMET® was evaluated in 580 patients (see Adverse Events Section for demographic description). Of these patients, 270 (244 men, 26 women) were studied in two randomized, blinded, placebo controlled clinical trials. These patients had a mean age of 67, and a range 22 to 87 years. Eligible patients had painful metastatic bone lesions that had failed other treatments, had at least a 6 month expected survival and had a positive radionuclide bone scan. Routine x-rays to evaluate the metastatic lesions were not part of the protocol.

In study A, 118 patients were randomized to receive 0.5 mCi/kg QUADRAMET® , 1.0 mCi/kg QUADRAMET® , or a placebo intravenous injection. In study B, 152 patients were randomized to receive either 1.0 mCi/kg QUADRAMET® or a placebo intravenous injection. Both studies were double blind over a 4 week period. Patients scored their daily pain intensity on a visual analogue scale rated from 0 (no or low pain) to 10 (excruciating pain). The area under the pain curve (AUPC) was obtained by integrating the daily pain scores by week. Opioid analgesic use was recorded daily and averaged over each week and expressed in oral morphine milligram equivalents.

Of the 270 patients studied, 232 (86%) had prostate cancer and 38 (14%) had other primary cancers. In study A, 80 (68%) of the patients had prostate cancer and 38 (32%) had a variety of other primary tumors. In study B, all (100%) patients had prostate cancer.

The results of the patients’ AUPC scores are shown in Table 3. In both trials for each of the 4 weeks of study, the mean AUPC scores decreased in patients who received QUADRAMET® (1.0 mCi/kg). In study A, pain (the AUPC) decrease from baseline was significantly different in QUADRAMET® 1.0 mCi/kg and placebo groups at weeks 3 and 4. In study B, pain (the AUPC) decrease from baseline was significantly different in QUADRAMET® 1.0 mCi/kg and placebo groups at weeks 2, 3 and 4.

Table 3: COMPARISON OF WEEKLY PAIN SCORES (a)AFTER QUADRAMET® 1.0mCi/kg or PLACEBO IV [Intent to Treat]
STUDY A (n = 73) (b) STUDY B (n = 150) (c)
WEEK

Placebo

N=36

1.0 mCi/kg

N=37

Placebo

N=50

1.0 mCi/kg

N=100

Baseline 26.5 (11.8) 28.7 (12.3) 28.5 (14.1) 28.1 (12.9)
1 26.1 (10.3) 27.6 (14.1) 27.9 (14.6) 25.8 (13.1)
2 24.4 (10.4) 23.8 (13.7) 28.1 (15.4) 20.6 (13.9)*
3 24.3 (11.0) 20.5 (11.5)* 25.8 (16.1) 20.1 (13.3)*
4 24.7 (12.1) 18.8 (10.8)* 24.7 (15.3) 19.9 (13.7)*
  • (a) Area Under the Pain Curve (SD).
  • (b) Excludes 5 patients with missing baseline or extreme values; and all 40 patients who received 0.5 mCi QUADRAMET®. QUADRAMET® 0.5 mCi/kg can not be distinguished from placebo.

  • (c) Excludes 2 patients with missing baseline values.

  • (*) Statistically significant difference in change from baseline in comparison to placebo.

In the two clinical trials, the patient use of analgesics differed. In Study A, the patients did not receive specific instructions on analgesic reduction. In Study B, patients were encouraged to adjust their pain medication as needed. As shown in Table 4, the morphine equivalent analgesic use in study A generally increased from baseline in both the QUADRAMET® and placebo treatment groups; however, the difference between the QUADRAMET® and placebo group change from baseline is not statistically significant. In study B, the placebo treated patients increased their use of opioid analgesics, while the QUADRAMET® treated patients decreased their use of opioid analgesics.

Table 4: COMPARISON OF WEEKLY MEAN ANALGESIC USE (a) BETWEEN QUADRAMET® 1.0 mCi/kg AND PLACEBO GROUPS [Intent to Treat]
STUDY A (n = 73) (b) STUDY B (n = 150) (c)
WEEK

Placebo

N=36

1.0 mCi/kg

N=37

Placebo

N=50

1.0 mCi/kg

N=100

Baseline 93.5 (154.0)(a) 127.1 (189.9) 78.4 (83.1) 96.5 (166.6)
1 106.8 (173.8) 125.7 (192.6) 84.5 (91.1) 93.5 (165.5)
2 127.1 (238.4) 144.8 (276.7) 85.6 (90.9) 82.9 (122.9)
3 133.9 (254.0) 146.6 (278.2) 100.1 (119.4) 79.6 (131.2)*
4 135.6 (222.0) 135.1 (274.0) 106.3 (161.0) 76.8 (132.3)*
  • (a) Mean Analgesic Use (SD) is in morphine equivalent units; 0 = none.
  • (b) Excludes 5 patients with missing baseline or with extreme values; and all 40 patients who received 0.5 mCi QUADRAMET®. QUADRAMET® 0.5 mCi/kg can not be distinguished from placebo.
  • (c) Excludes 2 patients with missing baseline values.

  • (*) Statistically significant difference in change from baseline in comparison to placebo.

In both studies, the numbers of patients who experienced any decrease in AUPC score without any increase in analgesic use at weeks 3 and 4 were also evaluated. In study A, this occurred in 20/37 (54%) of the patients who received QUADRAMET® 1.0 mCi/kg and 9/36 (25%) of the placebo treated patients. In study B, this occurred in 48/100 (48%) of the QUADRAMET® treated patients and 11/51 (22%) of the placebo treated patients.

INDICATIONS

QUADRAMET® is indicated for relief of pain in patients with confirmed osteoblastic metastatic bone lesions that enhance on radionuclide bone scan.

CONTRAINDICATIONS

QUADRAMET® is contraindicated in patients who have known hypersensitivity to EDTMP or similar phosphonate compounds.

WARNINGS

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®
Hemoglobin Leucocytes Platelets
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 103 µL, 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.

Page 2 of 4 « 1 2 3 4 »