Changes in prostate-specific antigen, markers of bone metabolism and bone scans after treatment with radium-223

Figures & data

Table 1. Baseline characteristics of 14 patients who received radium-223 (Ra-223) and four patients on placebo treatment.

Patient no.^a	EOD^b	PSA (<4 μg/l)	Total ALP (35–105 U/l)	Bone ALP (15–41 U/l)	1CTP (2.1–5.0 μg/l)
Ra-223 (n = 14)
1	3	255	159	70	6.8
2	1^c	166	49	39	4.8
3	3	243	170	82	6.4
4	2	87	79	67	9.5
5	3	3740	191	52	8.2
6	3	624	193	176	5
7	3	201	154	59	7.7
8	2	14	352	104	5.1
9	3	12	203	107	3.7
10	1	352	47	17	5.9
11	3	80	221	99	7.8
12	3	1010	439	248	29
13	3	75	254	284	3
14	NA^d	838	635	275	42
Placebo (n = 4)
15	2	388	46	10	6.6
16	2	3.6^e	167	45	6.3
17	3	845	483	293	9.4
18	3	4230	359	115	11
Median (range)		249 μg/l (3.6–4230 μg/l)	192 U/l (46–635 U/l)	90.5 U/l (10–293 U/l)	6.7 μg/l (3.0–42 μg/l)
No. of patients	EOD1: n = 2		14^f	15^f	14^f
	EOD2: n = 4
	EOD3: n = 11

^aPatients 4, 5, 6, 8 and 18 received localized radiotherapy during the study; patients 15–18 received placebo. ^bExtent of the disease (EOD): grade 1, <6 metastatic lesions all smaller than half a vertebra; grade 2, 6–20 lesions; grade 3, >20 lesions; grade 4, >75% of the skeleton involved. ^cMultiple bone lesions by computed tomography (CT). ^dNot available, but multiple bone metastases by CT. ^eProstate-specific antigen: 12 μg/l at randomization 2 weeks before first infusion. ^fNumber of values above normal range.

PSA = prostate-specific antigen; total ALP = total alkaline phosphatase; bone ALP = bone alkaline phosphatase; 1CTP = carboxy-terminal pyridinoline cross-linked telopeptide.

Table 2. Number of patients that received Ra-223 with changes of PSA, total-ALP and bone-ALP from baseline after three- and six months treatment.

	PSA (<4 μg/l)		Total-ALP (35–105 U/l)		Bone-ALP (15–41 U/l)		1CTP (2.1–5.0 μg/l)
Change	Ra-223	Placebo	Ra-223	Placebo	Ra-223	Placebo	Ra-223	Placebo
After 3 months
Increased	7	3	0	1	0	3	3	1
Unchanged	5	0	5	3	3	1	9	3
Decreased	2	1^a	9	0	11	0	2	0
Median  (range)	307 μg/l (15–4150 μg/l)		92 U/l (32–392 U/l)		33 U/l (10–199 U/l)		6.9 μg/l (4.6–21 μg/l)
After 6 months
Increased	11	3	3	2	1	3	8	1
Unchanged	3	0	5	2	2	1	3	3
Decreased	0	1^a	6	0	9	0	2	0
Median  (range)	415 μg/l (21–6950 μg/l)		149 U/l (40–360 U/l)		37 U/l (14–206 U/l)		8.3 μg/l (4.7–23 μg/l)
NA					2		1

^aPatient with local radiotherapy.

1CTP = carboxy-terminal pyridinoline cross-linked telopeptide; NA = not available.

Difference baseline versus 3 months: PSA, p = 0.048; total-ALP, p = 0.001; bone-ALP, p = 0.001; 1CTP, p = 0.7.

Difference baseline versus 6 months: PSA, p = 0.009; total-ALP, p = 0.198; bone-ALP, p = 0.015; 1CTP, p = 0.38.

Figure 1. Longitudinal changes (% from baseline, 0) of prostate-specific antigen (PSA), total alkaline phosphatase (total ALP) and bone alkaline phosphatase (bone ALP) during 6 months of therapy with radium-223 (Ra-223) (A: 14 patients) or placebo (B: four patients). (Several parts of individual curves overlap each other.) Dashed horizontal line indicates ≥30% increase from baseline; solid horizontal line indicates ≥30% reduction from baseline.

Table 3. Six month changes on [^99mTc]bisphosphonate bone scan.

Patient no.^a	No. of lesions
	EOD	New foci^b	Reduced ^99mTc uptake
Ra-223 (n = 12)
1	3	2	6
2	1	2	0
3	3	4	4
4	2	0	7
6	3	13	2
7	3	17	13
8	2	41	5
9	3	19	16
10	1	12	0
11	3	56	3
12	3	6	39
13	3	25	24
Placebo (n = 4)
15	2	5	1
16	2	31	1
17	3	8	3
18	3	43	0

^aPatient 14: missing pretreatment bone scan; patient 5: missing post-treatment bone scan; patients 15–18 received placebo. ^bIncludes expanded lesions.

EOD = extent of the disease.

Figure 2. Whole-body [^99mTc]bisphosphonates (HDP) bone scans for patient no. 13: pretreatment (left column A and C) and post-treatment (right column B and D), with anterior views (upper row A and B) and posterior views (lower row C and D). Development of new/expansion of existing lesions (n = 24) and concomitant reduced HDP uptake in pretreatment known lesions. Arrows point to C2 and Th7, further visualized by FACBC positron emission tomography/computed tomography; this examination was not available for the left thigh (broken arrow).

Figure 3. [¹⁸F]FACBC positron emission tomography/computed tomography fused images of C2 (upper row) and Th7 (lower row) for patient no. 13: pretreatment (left column) and post-treatment (right column). Tumour expansion with increased FACBC uptake (arrows) in areas of no/very weak uptake pretreatment, interpreted as new tumour tissue.