01.12.2017 | Research article | Ausgabe 1/2017 Open Access

BK-UM in patients with recurrent ovarian cancer or peritoneal cancer: a first-in-human phase-I study
- Zeitschrift:
- BMC Cancer > Ausgabe 1/2017
Electronic supplementary material
Background
Methods
Patient selection
Investigational drug
Study design
Safety evaluation and definition of DLT
Efficacy assessments
Pharmacokinetics
Measurement of HB-EGF levels in serum and abdominal fluid
Results
Patient characteristics
Patient no.
|
Cancer subtype
|
Previous chemotherapy
|
Previous radiotherapy
|
PS
|
---|---|---|---|---|
1
|
OVCA (EMC)
|
5 lines
|
None
|
1
|
2
|
OVCA (SCC)
|
2 lines
|
None
|
1
|
3
|
OVCA (SCC)
|
2 lines
|
None
|
1
|
4
|
OVCA (SCC)
|
1 lines
|
γ-knife
|
1
|
5
|
PC (SCC)
|
2 lines
|
None
|
1
|
6
|
OVCA (SCC)
|
3 lines
|
None
|
1
|
7
|
OVCA (SCC)
|
8 lines
|
None
|
0
|
8
|
OVCA (SCC)
|
7 lines
|
None
|
1
|
9
|
OVCA (SCC)
|
4 lines
|
None
|
1
|
10
|
OVCA (CCC)
|
5 lines
|
None
|
1
|
11
|
OVCA (TCC)
|
4 lines
|
None
|
0
|
Safety and tolerability
Level 1
|
Level 2
|
Level 3
|
|||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Patient no.
|
1
|
2
|
3
|
4
|
5
|
6
|
7
|
8
|
9
|
10
|
11
|
Appetite loss
|
2
|
2
|
|||||||||
General fatigue
|
2
|
||||||||||
Nausea
|
2
|
2
|
|||||||||
Vomiting
|
2
|
2
|
|||||||||
Ileus
|
2
|
3
|
|||||||||
Constipation
|
2
|
2
|
2
|
||||||||
Diarrhea
|
2
|
||||||||||
Abdominal pain
|
2
|
2
|
|||||||||
Abdominal fullness
|
2
|
3
|
|||||||||
Intraabdominal bleeding
|
2
|
||||||||||
Lumbago
|
2
|
||||||||||
Headache
|
2
|
||||||||||
Fever
|
2
c
|
2
c
|
|||||||||
Dyspnea
|
2
|
||||||||||
Hematoma
a
|
2
|
||||||||||
Erythema
|
2
|
||||||||||
Anemia
|
2
|
2
|
2
|
3
|
2
|
||||||
Elevation of ALT
|
2
|
||||||||||
Elevation of CRP
|
2
|
2
c
|
2
c
|
||||||||
Hypoalbuminemia
|
2
|
2
|
|||||||||
Hypotension
b
|
3
c
|
3
c
|
Dose escalation and MTD
Pharmacokinetics
Evaluation of response
Patient no.
|
HB-EGF in serum (pg/mL)
|
HB-EGF in abdominal fluid (pg/mL)
|
Serum CA125 (IU/mL)
|
Anti-diphtheria toxin antibodies (IU/mL)
|
Efficacy
|
||||
---|---|---|---|---|---|---|---|---|---|
Pre-Tx
|
Post-Tx
|
Pre-Tx
|
Post-Tx
|
Pre-Tx
|
Post-Tx
|
Pre-Tx
|
Post-Tx
|
||
1
|
1971
|
196
|
2169
|
106
|
291
|
137
|
<0.01
|
2.56
|
SD
|
2
|
556
|
349
a
|
416
|
560
a
|
1411
|
3487
|
<0.01
|
124
|
PD
|
3
|
297
|
172
|
593
|
292
|
46
|
50
|
<0.01
|
>131
|
SD
|
4
|
267
|
85
|
143
|
34
|
1408
|
2217
|
0.04
|
>131
|
PR
|
5
|
51
|
101
|
55
|
399
|
267
|
600
|
0.03
|
31.1
|
SD
|
6
|
74
|
109
|
109
|
171
|
254
|
158
|
<0.01
|
81.9
|
PD
|
7
|
67
|
79
|
130
|
ND
|
2813
|
3983
|
<0.01
|
0.06
|
PD
|
8
|
162
|
141
a
|
140
|
132
a
|
3894
|
5147
|
0.13
|
20.5
|
PD
|
9
|
231
|
130
|
237
|
66
|
1856
|
3984
|
0.01
|
1.02
|
PD
|
10
|
247
|
140
|
ND
|
ND
|
40
|
63
|
<0.01
|
>41.0
|
SD
|
11
|
67
|
155
a
|
ND
|
ND
|
16
|
94
|
<0.01
|
>6.56
|
SD
|
Patient no.
|
Conventional chemotherapy after BK-UM
|
Overall survival (months)
|
---|---|---|
1
|
CDDP + CPT-11 (6 courses)
|
28.1
|
2
|
–
|
3.4
|
3
|
CDDP + CPT-11 (6 courses)
|
24.3
|
4
|
CDDP + CPT-11 (6 courses)
|
15.1
|
5
|
–
|
5.5
|
6
|
–
|
5.0
|
7
|
CDDP + CPT-11 (2 courses)
|
7.4
|
8
|
CDDP + IFM (2 courses)
|
4.2
|
9
|
–
|
3.6
|
10
|
CPT-11 (6 courses)
|
14.0
|
11
|
CBDCA + Doxil (6 courses)
|
>60
a
|