28.01.2020 | Original Article – Clinical Oncology | Ausgabe 3/2020 Open Access

Should MMMT still be treated with adjuvant taxane-based combination chemotherapy?
- Zeitschrift:
- Journal of Cancer Research and Clinical Oncology > Ausgabe 3/2020
Electronic supplementary material
Publisher's Note
Introduction
Materials and methods
Cohort description and outcome analysis
Next-generation sequencing and immunohistochemistry
Statistical analyses
Results
MMMT-E
N=103
21.4%
|
EC
N=172
35.8%
|
MMMT-O
N=17
3.5%
|
OC
N=189
39.3%
|
Overall
P value
|
N
481
|
|
---|---|---|---|---|---|---|
Age (years)
|
||||||
Mean ± SD
|
68.8±11.2
|
66.6±11.8
|
68.2±12.0
|
63.3±12.9
|
0.001
|
481
|
BMI
|
||||||
Mean ± SD
|
28.9±7.8
|
33.5±10.5
|
26.5±6.7
|
26.6±6.0
|
< 0.001
|
274
|
FIGO stage
|
94
|
165
|
17
|
185
|
< 0.001
|
461
|
Stage I/II
|
61 (64.9%)
|
126 (76.4%)
|
3 (17.6%)
|
60 (32.4%)
|
250
|
|
Stage III/IV
|
33 (35.1%)
|
39 (23.6%)
|
14 (82.4)
|
125 (67.6%)
|
211
|
|
Grade
|
45
|
164
|
15
|
161
|
385
|
|
Grade 3
|
37 (82.2%)
|
55 (33.5%)
|
14 (93.3%)
|
107 (66.5%)
|
< 0.001
|
213
|
Other
|
8 (17.8%)
|
109 (66.5%)
|
1 (6.7%)
|
54 (33.5%)
|
172
|
|
Histotype
|
35
|
172
|
9
|
188
|
<0.001
|
404
|
Serous
|
10 (28.6%)
|
29 (16.9%)
|
4 (44.4%)
|
126 (67.0%)
|
169
|
|
Other
|
25 (71.4%)
|
143 (83.1%)
|
5 (55.6%)
|
62 (33.0%)
|
235
|
|
Chemotherapy
|
53
|
19
|
14
|
136
|
< 0.001
|
222
|
P/A
|
47 (88.7%)
|
6 (31.6%)
|
6 (42.9%)
|
20 (14.7%)
|
79
|
|
P/T
|
6 (11.3%)
|
13 (68.4%)
|
8 (57.1%)
|
116 (85.3%)
|
143
|
|
Adjuvant RT
|
95
|
98
|
17
|
15
|
< 0.001
|
222
|
Yes
|
62 (65.3%)
|
45 (45.9%)
|
0 (0%)
|
4 (26.7%)
|
111
|
|
RD
|
71
|
62
|
16
|
9
|
< 0.001
|
158
|
None
|
59 (83.1%)
|
53 (85.5%)
|
7 (43.8%)
|
6 (66.7%)
|
122
|
|
LND
|
95
|
74
|
15
|
8
|
< 0.001
|
192
|
Any
|
66 (69.5%)
|
43 (58.1%)
|
2 (13.3%)
|
5 (62.5%)
|
116
|
|
n.d.
|
29 (30.5%)
|
31 (41.9%)
|
13 (86.7%)
|
3 (37.5%)
|
76
|
|
DOD
|
32 (31.1%)
|
17 (9.9%)
|
6 (35.3%)
|
36 (19.0%)
|
< 0.001
|
91
|
Discussion
Authors
|
Journal (year)
|
N
|
Design
|
Disease
|
Treatment
|
Outcome
|
---|---|---|---|---|---|---|
Fowler, GOG Study Group
|
Gynecol Oncol (
2002)
|
28
|
Prospective
|
MMMT-E
Stage III/IV persistent or recurrent
|
Trimetrexate 5 mg/m
2 b.i.d. for 5 days and repeated in 14 days
|
Overall RR 4.8%.
|
Duska
|
Gynecol Oncol (
2002)
|
55
|
Retrospective
|
MMMT-O
Stage II–IV
|
Carboplatin/Paclitaxel
|
Complete CR 55%; OS 27.1 months
|
Thipgen, GOG Study Group
|
Gynecol Oncol (
2004)
|
136
|
Prospective
|
MMMT-O
|
Cisplatin (50 mg/m
2) every 3 weeks until progression or toxicity
|
RR 20%, similar to MMMT-E
|
Sutton, GOG Study Group
|
Gynecol Oncol (
2005)
|
76
|
Prospective
|
MMMT-E
Stage I/II
|
Ifosfamide 1.5 g/m
2 iv); Cisplatin 20 mg/m
2
|
5-year OS 62%
|
Miller, GOG Study Group
|
Gynecol Oncol (
2005)
|
51
|
Prospective
|
MMMT-E
Persistent or recurrent
|
Phase II Topotecan 1.5 mg/m
2 iv until progression or toxicity
|
No major activity
|
Homesley, GOG Study Group
|
JCO (
2007)
|
179
|
Prospective
|
MMMT-E
Stage III/IV persistent or recurrent
|
Phase III Ifosfamide 2.0 g/m
2 iv or Ifosfamide 1.6 g/m
2 iv and Paclitaxel 135 mg/m
2
|
Median PFS and OS, combination treatment 3.6 v 5.8 v 3.6 and 13.5 v 8.4 months
|
Leiser
|
Gynecol Oncol (
2007)
|
30
|
Retrospective
|
MMMT-O
Stage II–IV
|
Platinum and Taxane
|
5-year OS 30%
|
Wolfson, GOG Study Group
|
Gynecol Oncol (
2007)
|
206
|
Prospective
|
MMMT-E
Stage I–IV
|
WAI or 3 cycles of Cisplatin and Ifosfamide
|
Chemotherapy arm lower RR 21% and death rate 29%
|
Makker
|
Gynecol Oncol (
2008)
|
49
|
Retrospective
|
MMMT-E
Stage I–IV
|
Paclitaxel–Carboplatin; Ifosfamide–Platinum; other CT; RT concurrent or alone
|
Paclitaxel–Carboplatin most efficacious
|
Signorelli
|
Int J Gynecol Cancer (
2009)
|
41
|
Retrospective
|
MMMT-O
|
Cisplatin, Adriamycin, and Cyclophosphamide vs Cisplatin, Epirubicin, and Ifosfamide
|
Cisplatin, Adriamycin, and Cyclophosphamide:good RR but high toxicity
|
Hoskins
|
Gynecol Oncol (
2008)
|
39
|
Prospective
|
MMMT-E
|
Paclitaxel 175 mg/m
2, carboplatin (AUC 5-6) for 3-6 cycles ± radiation
|
RR 55–60%
|
Miller, GOG Study Group
|
Gynecol Oncol (
2010)
|
28
|
Prospective
|
MMMT-E
Persistent or recurrent
|
Phase II gemcitabine 600 mg/m
2 and Docetaxel 35 mg/m
2 iv days 1, 8 and 15 until progression or toxicity
|
Docetaxel and Gemcitabine not active
|
Galaal
|
Cochrane Database Syst Rev (
2011)
|
579
|
Retrospective
|
MMMT-E
Persistent or recurrent
|
RT and/or systemic chemotherapy
|
Chemotherapy with Ifosfamide and Paclitaxel should be considered
|
Lacour
|
Int J Gynecol Cander (
2011)
|
23
|
Prospective
|
MMMT-E
Persistent or recurrent
|
Phase II single arm 6 cycles of Carboplatin/Paclitaxel 3w
|
RR 62 %
|
Einstein
|
Gynecol Oncol (
2012)
|
27
|
Prospective
|
MMMT-E
|
Ifosfamide (1.2 g/m
2 and Cisplatin (20 mg/m
2 vs Ifosfamide alone 3 cycles followed by pelvic external beam RT and brachytherapy followed by 3 additional cycles
|
No significant activity
|
Aghajanian, GOG Study Group
|
Gynecol Oncol (
2012)
|
17
|
Prospective
|
MMMT-E
|
Paclitaxel 175 mg/m
2 iv, Carboplatin AUC 6, Iniparib 4 mg/kg iv until disease progression or toxicity
|
No significant activity
|
Campos, GOG Study Group
|
Gynecol Oncol (
2014)
|
22
|
Prospective
|
MMMT-E
Recurrence
|
Phase II, second-line Pazopanib orally 800mg
|
Minimal activity
|
Lorusso
|
Int J Gynecol Cancer (
2014)
|
46
|
Retrospective
|
MMMT-E
Stage I–IV
|
Cisplatin 20 mg/m
2 and Ifosfamide 1500 mg/m
2 vs Carboplatin AUC 5 and Paclitaxel 175 mg/m
2
|
Same efficiency but better toxicity profile with Carboplatin-Paclitaxel
|
Otsuki
|
Int J Gynecol Cancer (
2015)
|
51
|
Prospective
|
MMMT-E
Complete resection
|
Phase II single arm: 6 courses of 175 mg/m
2 Paclitaxel and Carboplatin AUC 6
|
Combination of Paclitaxel and Carboplatin feasible and effective, 78.2% PFS, 87.9% OS
|
Vandenput
|
Int J Gynecol Cancer (
2011)
|
69
|
Retrospective
|
MMMT-E and EC
Stage I–I complete Staging
|
Platinum-based CT or no adjuvant therapy
|
RFS better with Platinum-based CT 22 vs. 10 months
|
Mackay
|
Gynecol Oncol (
2012)
|
41
|
Prospective
|
MMMT-E MMMT-O
Sarcoma Metastatic disease
|
Phase II
VEGF TRAP (Aflibercept) Single Agent trial
|
Minimal activity
|