Transcript Uterine Corpus Malignancies Chemotherapy Update

Endometrial Committee
David Scott Miller, M.D., F.A.C.O.G., F.A.C.S.
Director and Dallas Foundation Chair in Gynecologic Oncology
Professor of Obstetrics & Gynecology
University of Texas Southwestern Medical Center
Dallas, Texas, U.S.A.
Resected Endometrial
• GOG0249: A Phase III Trial of Pelvic
Radiation Therapy versus Vaginal Cuff
Brachytherapy Followed by
Paclitaxel/Carboplatin Chemotherapy in
Patients with High Risk, Early Stage
Endometrial Cancer (23 Mar 2009)
– RTOG
Resected Endometrial
• PORTEC 3: Randomized Phase III Trial
Comparing Concurrent Chemoradiation
and Adjuvant Chemotherapy with Pelvic
Radiation Alone in High Risk and
Advanced Stage Endometrial Carcinoma
– MaNGO, ANZGOG, NRCI, NCIC-CTG, NSGO
Resected Endometrial
• GOG258 (UC0704): A Randomized Phase
III Trial of Cisplatin and Tumor Volume
Directed Irradiation Followed by
Carboplatin and Paclitaxel vs. Carboplatin
and Paclitaxel for Optimally Debulked,
Advanced Endometrial Cancer (29 Jun
2009)
– RTOG
Results of previous studies:
Pooled survival data
CSS endometrioid carcinomas POOLED DATA
0.87
0.75
1.00
Study proposal
0.50
0.25
HR 0.51 (95 % CI 0.29-0.91) p=0.02
0.00
NSGO
0.77
0
Number at risk
random = 0 187
random = 1 197
1
175
187
2
3
analysis time
153
164
random = 0
130
149
4
5
106
118
75
87
random = 1
The combination of RT + CT is better than RT
Proposed new study exploring if the combination
of RT and CT is superior to CT:
After 4 - A Phase III intergroup trial on adjuvant therapy in radically operated
endometrial cancer patients (FIGO stage IC-IIIC) with high risk for micrometastatic
disease
Thomas Hogberg, Lund Univ Hosp Oct 2009
Proposed study
Randomization
N=1000
Radical surgery
TAH+BSO±LA
CTx4
Main inclusion criteria
a. Endometrioid carcinoma
b. Stage 1C grade 3
c. Stage IIA grade 3 and MI≥50%, IIB
d. Stage IIIA-C
Radical surgery, LA recommended but
optional
Main exclusion criteria
Serous or clear cell carcinoma
IIIA with only pos fluid cytology
RT
CTx2
CT : Paclitaxel 175 mg/m2,
carboplatin AUC 5-6 (calculated)
q 3 weeks
Primary endpoint
Overall survival (OS)
Thomas Hogberg, Lund Univ Hosp Oct 2009
Pelvic Recurrence
• GOG0238: A Randomized Trial of Pelvic
Irradiation with or without Concurrent
Weekly Cisplatin in Patients with Pelviconly Recurrence of Carcinoma of the
Uterine Corpus
– RTOG, NCRI, SWOG
EN.8 - A PHASE III STUDY OF STANDARD
THERAPY VERSUS RIDAFOROLIMUS IN
WOMEN WITH RECURRENT OR METASTATIC
ENDOMETRIAL CANCER WHO HAVE
PREVIOUS HAD CHEMOTHERAPY
Interested Groups: ACRIN, AGO-AUST, AGO-OVAR,
ANZGOG?, DUTCH GOG, EORTC, GEICO, GINECO,
JGOG, MANGO, MITO, NCRI, NSGO, SWOG
Schema
R
A
Women with
N
recurrent or
D
metastatic
O
endometrial
M
cancer
I
1-2 Prior
Z
Chemotherapy
E
Arm 1: ridaforolimus 40 mg
po days 1-5 each week
Imaging
Disease
Survival
q8
progression follow-up
weeks
Arm 2:
medroxy progesterone 200 mg
or
megestrol 160 mg (as per local
practice) po daily
Chemotherapy options
Sample size: Approximately 460 patients
Carcinosarcoma
GOG0261: Randomized Phase III Trial of
Carboplatin plus Paclitaxel versus
Ifosfamide plus Taxol in Patients with
Advanced, Persistent or Recurrent
Carcinosarcoma
NCRI, GINECO, JGOG, RTOG
GTN
• Charge from the Executive
• RFP
• ISSTD
GTD Concepts
• Hydatidiform Mole Registry (Quinn)
• Pulse Act-D vs. 8 day MTX for Low Risk
GTN