WOMEN'S HEALTH
that the message is getting out across the country to those of us in
the gynecology community, so we do what we can to decrease the
incidence of fallopian tube and ovarian cancer.
For those diagnosed with fallopian tube and ovarian cancer,
patients are living longer. Our specialty has learned to individualize
therapy. Options for upfront therapy for patients with stage III or
IV-A disease include tumor debulking followed by chemotherapy,
for patients who are surgical candidates, versus neoadjuvant che-
motherapy followed by interval debulking, for patients with disease
not amenable to debulking or decreased performance status. Studies
have shown equivalent results with either approach. There are a va-
riety of options for chemotherapy including intravenous paclitaxel/
carboplatin versus dose dense chemotherapy versus intraperitoneal
chemotherapy. The type, schedule and route of chemotherapy can
be tailored to the patient.
Two options for treatment of recurrent fallopian tube, peritoneal
or ovarian cancer have given us reason for hope. Bevacizumab,
which is an anti-vascular endothelial growth factor antibody, binds
vascular endothelial growth factor and inhibits new blood vessel
formation (angiogenesis) by tumor. Bevacizumab has benefit as a
targeted monotherapy, but it also has benefit combined with che-
motherapy. GOG-218, OCEANS TRIAL, AURELIA TRIAL, and
GOG-213 all showed improved progression free survival in patients
treated with bevacizumab. This benefit was seen in patients whose
cancer recurred longer than six months from completion of initial
chemotherapy as well as those whose cancer recurred within six
months of completion of chemotherapy [4,5]. Bevacizumab is used
with chemotherapy with recurrent disease as well as maintenance
therapy after completion of the chemotherapy. In GOG-213, the trial
had overall survival as an endpoint and the addition of bevacizumab
appeared to improve median overall survival in platinum-sensitive
recurrent ovarian cancer in a sensitivity analysis.
The other exciting treatment option for recurrent ovarian can-
cer is the approval of poly (ADP-ribose) polymerase inhibitors
(PARP-I). Up to 50 percent of all serous ovarian carcinomas have
homologous recombination deficiency, which is a defect in DNA
repair. If a tumor is unable to repair DNA, it will be more sensitive
to treatments that cause damage to DNA. The poly (ADP-ribose)
polymerase enzymes function in DNA repair. Therefore, PARP-I
create a build-up of damaged DNA which leads to cell death. Sev-
eral studies have shown a significant improvement in progression
free survival in patients with platinum-sensitive recurrent ovarian
cancer with BRCA mutations as well as patients whose tumor was
“BRCA like” who were treated with either PARP-I alone or with
PARP-I following treatment with chemotherapy [6].
Another area of developing treatment for ovarian cancer is im-
munotherapy. One method that is being investigated is the use of
tumor infiltrating lymphocytes taken from the patient, increasing
these cells’ specificity for anti-tumor effects, then transferring them
back into the patient. The other method that is more advanced in
development involves checkpoint inhibitors. Checkpoint inhibitors
block the programmed death 1 (PD-1) receptor or its ligand (PD-L1).
This receptor and its ligand allow the tumor to suppress our immune
system so we do not recognize the tumor as a foreign invader. If we
inhibit or kill off this receptor/ligand, then our immune systems
will recognize, target and destroy the tumor. Immunotherapy is
an exciting area of research that gives us hope for the future [7].
Vaccines are also being investigated.
The crisis in our fight against ovarian cancer is the lack of cur-
rent research funding to develop further treatment options and
funding for research trials. My hope is this article will reach not
just physicians, but also people in the community who can reach
out of our Congressional representatives to encourage them to
make a difference. In my life and career, I have been changed by
the courageous women with gynecologic cancer. We owe it to the
brave women with ovarian cancer who have lost the fight, those
who are currently fighting, and those who one day will face this
fight for a cure.
References:
1. Childers, CP, Childers KK, Maggard-Gibbons, M, et al. National
estimates of genetic testing in women with a history of breast
or ovarian cancer. J Clin Oncol. 2017; 35:3800-6.
2. Walker, JL, Powell B, Chen L, et al. Society of gynecologic on-
cology recommendations for the prevention of ovarian cancer.
Cancer. 2015; 121:2108-2120.
3. Powell, CB, Alabaster, A, et al. Salpingectomy for sterilization.
Obstet Gynecol. 2017; 130:961-7.
4. Wu, YS, Shiu, L, et al. Bevacizumab combined with chemo-
therapy for ovarian cancer: an updated systematic review and
meta-analysis of randomized controlled trials. Oncotarget.2017;
8: 10703-13.
5. Coleman, RL, Brady MF, Herzog, TJ, et al. Bevacizumab and
paclitaxel-carboplatin chemotherapy and secondary cytore-
duction in recurrent, platinum-sensitive ovarian cancer (NRG
Oncology/Gynecologic Oncology Group study GOG-0213):
a multicentre, open-label, randomized, phase 3 trial. Lancet
Oncol. 2017; 18:779-791.
6. Swisher, EM, Lin KK, Oza AM, et al. Rucaparib in relapsed,
platinum-sensitive high-grade ovarian carcinoma (ARIEL2
Part 1): an international,multicentre, open –label, phase 2 trial.
Lancet Oncol. 2017; 18:75-87.
7. Herzog, TJ, Ison G, Alvarez, RD, et al. FDA ovarian cancer
clinical trial endpoints workshop: A Society of Gynecologic
Oncology White Paper. Gynecol Oncol. 2017; 147:3-10.
Dr. Parker practices Gynecologic Oncology at Norton Cancer Institute.
OCTOBER 2018
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