Online Resource 1: Supplemental Fig. 1, Supplemental Table 1, and Supplemental Fig. 2
(Note: Presented in the order that they are referred to in the article)
Journal Name: European Journal of Nuclear Medicine and Molecular Imaging
Article Title: Phase I pharmacokinetic and biodistribution study with escalating doses of
Radium-223 dichloride in men with castration-resistant metastatic prostate cancer
Author Names and Affiliations: Jorge A. Carrasquillo1,2*, Joseph A. O’Donoghue3*, Neeta
Pandit-Taskar1,2, John L. Humm3, Dana E. Rathkopf4,5, Susan F. Slovin4,5, Matthew J.
Williamson3, Kristine Lacuna,4 Anne-Kirsti Aksnes6, Steven M. Larson1,2, Howard I. Scher4,5,
Michael J. Morris4,5
1
Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan-Kettering
Cancer Center and 2 Department of Radiology, Weill Cornell Medical College, New York, NY;
3
Department of Medical Physics, Memorial Sloan-Kettering Cancer Center; 4Genitourinary
Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New
York, NY; 5 Department of Medicine, Weill Cornell Medical College, New York, NY; 6Algeta ASA,
Oslo, Norway.
*co first authors contributed equally to the work
Corresponding Author Information: Jorge A. Carrasquillo M.D.
Memorial Sloan-Kettering Cancer Center
1275 York Avenue
New York, NY 10065
Phone: 212-639-2459
Fax: 212-717-3263
Email: carrasj1@mskcc.org
%ID/L plasma
10
1
0.1
0.01
0
24
48
72
96
120
144
168
Time (h)
Supplemental Fig. 1 Activity in plasma was converted to %ID/L of plasma. Mean and standard
deviation were plotted at the corresponding nominal times for all patients.
Supplemental Table 1. Adverse Events on patient level (N=10 patients)
Grade 1
Adverse Event
No. of
Patients
Grade 2
%
No.
%
Grade 3
Grade 4
Total
No.
%
No.
%
No.
%
BLOOD AND LYMPHATIC SYSTEM DISORDERS
Anemia
2
20%
3
30%
1
10%
0
0%
6
60%
Leukopenia
4
40%
0
0%
2
20%
1
10%
7
70%
Neutropenia
0
0%
0
0%
1
10%
0
0%
1
10%
Platelet count
decreased
2
20%
0
0%
1
10%
0
0%
3
30%
GASTROINTESTINAL DISORDERS
Diarrhea
3
30%
1
10%
2
20%
0
0%
6
60%
Nausea
2
20%
2
20%
1
10%
0
0%
5
50%
Vomiting
1
10%
1
10%
0
0%
0
0%
2
20%
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS
Fatigue
2
20%
3
30%
0
0%
0
0%
5
50%
Pneumonia
0
0%
0
0%
0
0%
1
10%
1
10%
Urinary tract
infection
0
0%
0
0%
1
10%
0
0%
1
10%
Blood albumin
decreased
2
20%
1
10%
0
0%
0
0%
3
30%
Aspartate
aminotransferase
increased
0
0%
0
0%
1
10%
0
0%
1
10%
Blood calcium
decreased
2
20%
2
20%
1
10%
0
0%
5
50%
Blood creatine
increased
0
0%
2
20%
0
0%
0
0%
2
20%
Blood glucose
increased
3
30%
1
10%
0
0%
0
0%
4
40%
INFECTIONS
INVESTIGATIONS
Blood potassium
decreased
2
20%
0
0%
0
0%
0
0%
2
20%
Blood sodium
increased
1
10%
1
10%
0
0%
0
0%
2
20%
Blood sodium
decreased
2
20%
0
0%
0
0%
0
0%
2
20%
Hemoglobin
decreased
1
10%
1
10%
0
0%
0
0%
2
20%
Blood phosphorus
decreased
0
0%
2
20%
0
0%
0
0%
2
20%
Blood alkaline
phosphatase
increased
0
0%
2
20%
0
0%
0
0%
2
20%
0
0%
0
0%
0
0%
4
40%
METABOLISM AND NUTRITION DISORDERS
Anorexia
4
40%
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS
Arthralgia
1
10%
2
20%
0
0%
0
0%
3
30%
Back pain
0
0%
1
10%
2
20%
0
0%
3
30%
20%
0
0%
1
10%
0
0%
3
30%
0
0%
0
0%
2
20%
NERVOUS SYSTEM DISORDERS
Peripheral motor
neuropathy
2
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS
Dyspnea
0
0%
2
20%
2A
2B
BEST BONE ALKALINE PHOSPHATASE RESPONSE DURING ACTIVE
TREATMENT (N=10 PATIENTS)
BEST PSA RESPONSE DURING ACTIVE TREATMENT
(N=10 PATIENTS)
0%
20%
0%
Cohort 1
-20%
Cohort 2
-40%
Cohort 3
-60%
-80%
-100%
Patient
Change in Bone Alkaline Phosphatase from
baseline (%)
Change in PSA from baseline (%)
40%
-10%
-20%
-30%
Cohort 1
-40%
Cohort 2
Cohort 3
-50%
-60%
-70%
-80%
Patient
Change in Serum N-telopeptide level from
baseline (%)
2C
BEST SERUM N-TELOPEPTIDE RESPONSE DURING ACTIVE
TREATMENT (N=10 PATIENTS)
30%
20%
10%
0%
Cohort 1
-10%
Cohort 2
-20%
Cohort 3
-30%
-40%
-50%
-60%
Patient
Supplemental Fig. 2: Waterfall plot showing: A) PSA response during treatment. PSA declines were greatest for the 2 patients at the highest
doses. B) Changes in bone alkaline phosphatase response during treatment. Decline in alkaline phosphatase was seen in all patients. C) Changes
in serum N-telopeptide response during treatment. Decline in serum N-telopeptide was seen 7 of 10 patients.