Palliative C are i n

Gynecologic Oncology
Mary M. Mullen, MD, James C. Cripe, MD, Premal H. Thaker, MD, MS*

KEYWORDS
 Palliative care  Palliative care economics  Palliative care barriers
 End-of-life symptom management

KEY POINTS
 Early palliative care is formally endorsed by the American Society of Clinical Oncology and
the Society of Gynecologic Oncology.
 Palliative care and anticancer or disease-modifying treatment are not mutually exclusive
and should occur concomitantly.
 The most efficient palliative care model consists of primary palliative care provided by the
primary oncologist and secondary palliative care provided by a separate specialty pallia-
tive care team.
 Gynecologic oncologists should be well versed in common symptom management.
 The transition to hospice at end of life is an important aspect of palliative care and stan-
dard gynecologic oncology care for patients with advanced gynecologic malignancy.

INTRODUCTION

Palliative care is patient- and family-centered care that optimizes quality of life by
anticipating, preventing, and treating suffering.1 Improving quality of life of patients
and their families should remain critically important for any serious diagnosis. The
goals of palliative care are demonstrated by the nine domains outlined by the Amer-
ican Association of Hospice and Palliative Medicine. These domains include rapport
and relationship building with patients and family caregivers, symptom distress and
function status management, exploration of understanding and education of prog-
nosis, clarification of treatment goals, assessment and support of coping, assistance
with medical decision making, coordination with other providers, and provision of
referrals to other providers.2 These goals should be addressed near the time of

The authors have no commercial or financial conflicts of interest regarding this topic.
Funding Sources: None.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington
University School of Medicine, Alvin J. Siteman Cancer Center, 660 South Euclid Avenue, Mail
Stop 8064-37-905, St Louis, MO 63110, USA
* Corresponding author.
E-mail address: thakerp@wustl.edu

Obstet Gynecol Clin N Am 46 (2019) 179–197

https://doi.org/10.1016/j.ogc.2018.10.001 obgyn.theclinics.com
0889-8545/19/ª 2018 Elsevier Inc. All rights reserved.
180 Mullen et al

diagnosis as demonstrated by the quality of life and survival benefits in the landmark
trial by Temel and colleagues3 evaluating palliative care within 8 weeks of diagnosis
with metastatic non–small cell lung cancer. The previously stated guidelines are
supported and strongly endorsed by many oncologic professional societies. The
American Society of Clinical Oncology (ASCO) is committed to facilitating the integra-
tion of palliative cancer care into existing health care systems worldwide to realize the
vision of comprehensive cancer care by 2020. Additionally, the Society of Gynecologic
Oncology (SGO) continues to make efforts promoting education and research in palli-
ative care for trainees and providers.4
In 2016 ASCO released evidence-based recommendations regarding the incorpo-
ration of palliative care into standard gynecologic oncology care. Key recommenda-
tions include the following: “Patients with advanced cancer, whether inpatient or
outpatient, should receive dedicated palliative care services, early in the disease
course, concurrent with active treatment. Referring patients to interdisciplinary pallia-
tive care teams is optimal, and services may complement existing programs.
Providers may refer caregivers of patients with early or advanced cancer to palliative
care services.” ASCO supports the delivery of services via interdisciplinary palliative
care teams in any treatment setting.5
The SGO echoes these recommendations and states that the delivery of palliative
care is essential in delivering quality care to women with gynecologic cancer.6 The
SGO has established 11 Principles of Palliative Care:
1. Express sensitivity to cultural differences and deliver palliative care with compas-
sion, empathy, and respect for a woman as an individual.
2. Establish open communication with women and their families providing the infor-
mation necessary to understand their condition, prognosis, and treatment
options.
3. Alleviate pain and distressing symptoms, whether physical or emotional, main-
taining hope and leading to an improvement in the woman’s quality of life.
4. Recognize that a multidisciplinary approach using the services of professionals
trained in psychological, social, and spiritual issues optimizes care and well-
being.
5. Respect a woman’s decision regarding acceptance or refusal of further treatment.
6. Recognize the practitioner’s responsibility to fully inform women of treatments un-
likely to achieve benefit or do harm.
7. Encourage women and families to consider hospice care as an option when
appropriate.
8. Understand and support the woman’s preferences regarding end-of-life care.
9. Maintain continuity of care for terminally ill women, avoiding feelings of isolation
and abandonment for the woman and her family.
10. Acknowledge the effect that end-of-life care has on the family and provide
emotional support including access to social and bereavement services.
11. Recognize that although providing palliative care is emotionally rewarding it is
crucial to acknowledge the potential for compassion fatigue and the need to sup-
port each other including members of the multidisciplinary team to remain fully
engaged.

DELIVERY OF PALLIATIVE CARE

Gynecologic oncologists deliver medical and surgical treatments of complex illnesses

and through this process frequently treat patients from diagnosis to the end of life. De-
livery of palliative care should be provided by the gynecologic oncologist managing
 Palliative Care in Gynecologic Oncology 181

the patient’s illness (primary palliative care) and by providers with dedicated training in
palliative care (specialty palliative care).7 In 2006, Hospice and Palliative Medicine
became a recognized specialty by the American Board of Medical Specialties, with
the American Board of Obstetrics and Gynecology as one of the sponsoring boards.
The unique relationship between the gynecologic oncologist and palliative care physi-
cian was further characterized in an in-depth qualitative interview study at six National
Cancer Institute–designated cancer centers. Thirty-four gynecologic oncologists
participated and two main themes were identified. Gynecologic oncologists value
the palliative care clinician’s communication skill and third-party perspective to in-
crease prognostic awareness and help negotiate differences between patient prefer-
ences and provider recommendations. Additionally, they would prefer specialty
palliative care services embedded within gynecologic oncology clinics.8 Throughout
the patient’s cancer course, treatment with curative intent should be paired with palli-
ative care for symptom relief, and ultimately, palliative care should be paired with hos-
pice at the end of a disease course (Fig. 1).

BENEFITS OF PALLIATIVE CARE

When delivered in a timely fashion, palliative care offers benefits to patients and their
families by improving symptom burden and quality of life. These benefits are associ-
ated with less aggressive care at the end of life, which limits overall costs, and inter-
estingly, this shift in care may be associated with prolonged survival.3

Fig. 1. Integration of palliative care into treatment with curative intent and end-of-life care.
182 Mullen et al

Palliative care has been shown to improve symptom burden in other malignancies,
most notably dyspnea in patients with lung cancer.9 Symptom distress and functional
status management is a complex problem in treating women with gynecologic malig-
nancies; however, they also quickly benefit from specialty palliative care. A retrospec-
tive review of women with gynecologic malignancies admitted to hospital and had a
palliative care consultation found improvement of symptom burden scored by the
Edmonton Symptom Assessment System. They had statistically significant improve-
ment in the frequency of moderate-to-severe symptoms in pain, anorexia, fatigue,
and nausea from initial palliative care consultation to hospital discharge.10 These ben-
efits are not limited to inpatient admissions. In a similar study 78 women with gyneco-
logic malignancies were followed in an outpatient palliative care clinic. Improvement in
pain, fatigue, anxiety, depression, nausea, drowsiness, appetite, and shortness of
breath were found to be statistically significant.11

End of Life and Hospice

Ultimately, to maximize survival, quality of life, and cost benefits of hospice, patients
should transition to hospice when their life expectancy is less than 6 months. The
literature, albeit limited, suggests 20% to 60% of gynecologic oncology patients
die on hospice with a median length of stay in hospice only 19 to 25 days with
55% of patients enrolling less than 30 days before death.12,13 Although patients
may qualify for hospice, in a review of 268 gynecologic oncology patients admitted
in the last 6 months of life, 70.5% were referred to hospice with a median time of
enrollment to death of only 22 days suggesting earlier referral may be appropriate.14
Per a 2010 study by Barbera and colleagues,15 51% of women with gynecologic can-
cer died in an acute care bed as an inpatient and according to two separate studies
up to 60% of patients have an invasive procedure performed within the last 3 to
6 months of life.16 End-of-life patients not managed on hospice are more likely to
be inpatient, transferred to the intensive care unit, and receive invasive procedures
without survival benefit.17 Thus, to provide optimal end-of-life care, timely hospice
referral is essential.
Although palliative care encompasses building rapport, clarification of goals, and
improvement of patient understanding, which are most critical at the end of life, signif-
icant benefits of early introductions have been documented in the existing literature.
Doll and colleagues18 reviewed end-of-life discussions and found that when outpa-
tient hospice discussions occurred, future admissions had a shorter length of stay
and increased use of palliative care resources. Nevadunsky and colleagues19 showed
that specialty palliative care improved hospice use from 41% to 72%; however, if pa-
tients received specialty palliative care consultation within 14 days of death, there was
no difference in aggressive measures or hospice use. Hospice enrollment was asso-
ciated with a decrease in this rate to 3% of patients receiving a procedure, chemo-
therapy, or radiation within the last 6 months of life and a decrease in inpatient
hospitalizations near end of life.14
Limiting futile chemotherapy, decreasing admissions, and increasing hospice use
have a tremendous benefit of decreasing costs associated with end-of-life care. Lewin
and colleagues20 reviewed 84 women with ovarian cancer, 17 were enrolled in hospice
and 67 were not. There was no significant difference in mean survival (32.4 vs
40.8 months; P 5 .30). However, nonhospice patients as compared with those
enrolled in hospice consume significantly more resources in the last 60 days of life.
These resource expenditures totaled $52,319 and $15,164, respectively. Most
recently, Urban and colleagues21 used the Surveillance, Epidemiology, and End Re-
sults Medicare database to review 5509 patients with ovarian cancer. On multivariate
 Palliative Care in Gynecologic Oncology 183

analysis, factors associated with increased cost in the last 90 days of life included
medical comorbidity, chemotherapy, time spent admitted, and admissions associated
with emergency room visits. They concluded reducing chemotherapy and increasing
hospice services will aid in lowering costs. Time on hospice has a maximal cost benefit
for oncology patients enrolled in hospice at least 58 days before death.22
Mechanisms must be identified to improve hospice use in the gynecologic oncology
population to improve patient outcomes. Physicians are often the advocates to hos-
pice enrollment and therefore it is critical that physicians partner with palliative care
services and initiate end-of-life conversations before symptoms or a patient becoming
unstable. Further research is necessary to determine how to improve hospice uptake
in the patient population.

LOGISTICS OF EARLY INTEGRATION OF PALLIATIVE CARE

Barriers to Palliative Care
The benefits of early integration of palliative care into standard gynecologic oncologic
care have been well established.10,12,17,23–26 However, barriers to palliative care can
make this integration extremely difficult. In fact, only 70.5% of gynecologic oncology
patients are referred to hospice or palliative care before death and only 18% have
palliative consultation within 30 days before death.12 To determine methods to over-
come these barriers it is important to first identify and define them.
Barriers to palliative care and/or hospice referral are multifactorial and include
physician factors, patient factors, and institutional factors (Box 1).
Physician factors
Physicians are usually the gatekeepers of palliative care referral. Seventy percent of
physicians report not fully understanding the benefits of palliative care and 73% of gy-
necologic oncologists report having fear that referral to palliative care will cause pa-
tients and families to feel abandoned, as if the physician has given up hope for the
patient.17,27,28 As a result, referral is often postponed until patients are symptomatic

Box 1
Barriers to the integration of palliative care into standard gynecologic oncology care

Physician Factors
Optimistic view of patient’s life expectancy
Lack of awareness of palliative care/lack of training
Fear of upsetting patient
Admission of failure
Patient Factors
Optimistic view of patient’s life expectancy
Lack of understanding of the meaning of palliative care
Fear of upsetting the physician
Institutional Factors
Inadequate resources
Poor reimbursement for palliative care services
Minimal formal training in palliative care for physicians
Late palliative care referrals
184 Mullen et al

or until all anticancer treatments are exhausted.29 Additionally, late palliative care or
hospice referral often occurs as a result of a falsely hopeful view of the patient’s
remaining life expectancy.17,30,31 Data demonstrate physicians regularly overestimate
survival in terminally ill patients with cancer.32

Patient factors
Patient and family reluctance to palliative care enrollment is largely centered
around the association of palliative care with death.29 In fact, many patients and
families consider palliative care to be equivalent to end-of-life care, and therefore
assume it is discordant with oncologic therapy.33 Because of an often overly opti-
mistic view of a patient’s or loved-one’s prognosis palliative care is often forgone.
Further reluctance occurs from fear of offending their physician by suggesting or
using palliative care.29 In a survey study of the SGO, 54% of respondents stated
that unrealistic patient expectations were always or often a barrier to quality end-
of-life care.34

Institutional factors
Institutional factors include limited resource availability and inadequate formal training
of physicians. Palliative care services, specifically outpatient services, are common in
most National Cancer Institute–designated cancer centers and academic settings, but
are much less available in community hospitals and rural areas.29,35 This is likely a
result of poor reimbursement and limited institutional budgets for palliative care ser-
vices.17,35 Furthermore, unawareness of available resources and ignorance regarding
how to use or provide these services creates additional barriers. Formal training in
palliative care and hospice for oncologists is minimal with only 11% of gynecologic
oncology fellows reporting palliative care training.36 A total of 77% of gynecologic on-
cologists report additional training during fellowship would better prepare them to pro-
vide end-of life care.37 As a result of these institutional barriers, referral often occurs
late, on average only 30 to 60 days before death, limiting a palliative care program’s
maximum potential.17,38

Practical Models of Palliative Care

Establishing effective and practical models of palliative care will work to overcome
known barriers. The National Comprehensive Cancer Network (NCCN) task force
and ASCO and SGO recognize and emphasize that palliative care and anticancer or
disease-modifying therapy are not mutually exclusive and should occur concomi-
tantly. These professional organizations suggest palliative care should be provided
from diagnosis to death in the form of bereavement support or to survivorship.5,24,39
Simultaneously, the World Health Organization (WHO) definition of palliative care
has evolved so the recipient of palliative care no longer needs to have an incurable
illness.40 The WHO emphasizes that palliative care is most effective in combination
with other oncologic therapies. These contemporary definitions aim to integrate palli-
ative care at a time during a patient’s cancer when a cure is still a possibility.
The most efficient palliative care model consists of the oncologist and specialty
palliative care, which allows the most relevant team to deliver care at the most appro-
priate time. The consulting palliative care teams are either independent or within the
primary oncology clinic and should be present in the inpatient and outpatient setting
to obtain maximum benefit.29 Studies suggest the integration of consultants within the
primary oncology clinic augments communication between the two teams and unifies
a patient’s care.5 These palliative care teams should be interdisciplinary consisting of
at least a palliative care physician and a palliative care nurse. They often also include
 Palliative Care in Gynecologic Oncology 185

social workers, physical therapists, occupational therapists, chaplains, counselors,

and/or rehabilitation medicine physicians.5,41
The bow tie model of palliative care illustrates the priorities emphasized by the
NCCN, ASCO, SGO, and the WHO (Fig. 2).42 It demonstrates the dynamic need for
varying balances of disease management and palliative care throughout a patient’s
illness. It also exhibits the gradual shift in focus as a patient’s disease progresses.
This model differs from archaic models in that palliative care is an integral part of early
disease management and survivorship is included as a possible outcome. This allows
patients to accept palliative care while cure is still a possibility, which is much less
intimidating to patients.
This palliative care model can only work by establishing the roles of the different
health care professionals involved in providing disease management and palliative
care. Although it may seem ideal for palliative care specialists to provide all palliative
facets of care, this is not sustainable. The increasing demand would certainly exhaust
the supply of services. Furthermore, having a consultant provide all palliative services
would likely fragment care and undercut oncologist-patient relationships.43
The oncologist should take responsibility for primary palliative care, and specialty
palliative care should be carried out by consulting services.43 Primary palliative care
services include early management of pain, depression, anxiety, and other basic
symptoms, and discussions about prognosis and goals of care. Specialty palliative
care services are more complex and include management of refractory or multifaceted
symptoms and conflict resolution between patients/families and treatment team.
These services also are appropriate in addressing futile treatments and intricate
end-of-life issues.43 Once each health care worker recognizes and understands his/
her role, this palliative care paradigm can reach its full potential.38 In this synchronized
model the oncologist provides early and basic palliative care needs and consults the
specialty palliative care team for more complex issues.44 Once placed, a successful
palliative care consultation should provide an initial and then ongoing assessment
evaluating the patient’s quality of life, symptom management, and goals of care.3

Timing of palliative care consultation

Only 18% of gynecologic oncology patients receive consultation greater than 30 days
before death.12 Although a gynecologic oncologist can provide primary palliative care
it is likely that specialty services are needed as a patient progresses through her
disease. Referral to specialty palliative care services should be made when “physical,
social, psychological, or spiritual unmet needs” are not able to be effectively managed
by the primary team.29 Of note, this may be at a time when the goal of disease man-
agement is still curative. This implies that oncologists must regularly assess patient’s
and caregivers’ needs to ensure timely referral to specialty palliative care services.
Timely referral results in added benefits specifically in patients with advanced malig-
nancies.3,9 Of note, gynecologic oncologists often defer palliative care referral until pa-
tients have a high disease and symptom burden and are near the end of life. Erring on
the side of earlier referral results in improved outcomes.10 ASCO specifically recom-
mends palliative care consultation within 8 weeks of the diagnosis of advanced or
metastatic cancer.3,5

Palliative care reimbursement

Reimbursement specifically for primary palliative care services is minimal. It is only
recently that reimbursement is available for primary palliative care services, such as
advanced care planning discussions.35 Regarding specialty palliative care services,
palliative care is a board-certified specialty that is reimbursed similarly to other
 186
Mullen et al
Fig. 2. The bow tie model of palliative care. (From Hawley PH. The bow tie model of 21st century palliative care. J Pain Symptom Manage 2014;47(1):
e3–4; with permission.)
 Palliative Care in Gynecologic Oncology 187

medical specialties with a unique Medicare billing identifier. Accordingly, a physician

and/or a midlevel provider can bill for their time directly. However, other members of
the interdisciplinary team, such as chaplains, social workers, and physical and occu-
pational therapists, cannot. Therefore, other forms of compensation are made for
these services.41 Unfortunately, the enormous cost savings that occur as a result of
patients receiving palliative care are not directly reallocated to support palliative
care services.29

Disparities of Palliative Care

It has been established that minority patients with cancer unjustly experience
increased comorbidities, are more likely to receive inferior quality of care, and are
less like to be insured.5 Although studies regarding disparities in palliative care are
sparse, limited data suggest that, similar to other care, minority patients are less likely
to receive equivalent palliative care. Studies document minorities have decreased
satisfaction with palliative care and worse pain management when compared with
their nonminority counterparts. In fact, compared with whites, minorities are more
likely to be hospitalized and receive intensive care unit care in the last 6 months of
life.45 Medicaid patients are less likely to receive “quality-adherent palliative care”
when compared with Medicare patients.46 Furthermore, patients of minorities and
low socioeconomic status are more likely to experience geographic disparities,
such as living in an area that does not have access to palliative care services. White
persons are overrepresented in all studies to date regarding palliative care outcomes,
and further research is necessary to better understand disparities that exist within
palliative care.5

STRATEGIES TO IMPROVE USE OF PALLIATIVE CARE

Despite the benefits, palliative care and hospice are grossly underused in gynecologic
oncology, and it is important to understand strategies to improve use of palliative care
and hospice. The strategies proposed would be most effective if used simultaneously.

Triggers to Referral
Many gynecologic oncologists do not have the training to complete a thorough pri-
mary palliative care assessment or to address palliative care needs once they are
recognized. Therefore, identifying specific triggers for palliative care referral would
likely improve the use of these services and quality outcomes. Adelson and col-
leagues47 demonstrated that the standardized use of triggers for palliative care
consultation among hospitalized patients resulted in decreased 30-day readmission
rates, decreased chemotherapy after discharge, increased hospice referrals, and
increased use of ancillary palliative care services on discharge. Similarly, in response
to the need to better identify patients requiring specialized palliative care services, the
Center to Advance Palliative Care assembled a consensus panel in 2010 to establish
key triggers for palliative care referrals among hospitalized patients. These triggers
include primary and secondary triggers. Primary triggers include frequent admissions,
admission prompted by difficulty to control symptoms, complex care requirements,
and decline in function. Secondary triggers include metastatic or incurable cancer,
chronic oxygen use, admission from long-term care facility, and limited social support.
Although these triggers were identified specifically for inpatients, these criteria are
certainly pertinent to gynecologic oncology patients in the outpatient setting.48 These
triggers should be evaluated early and regularly in all gynecologic oncology patients
regardless of diagnosis or symptoms to identify even patients with early stage disease
188 Mullen et al

who would benefit from these services. This approach considers the patient’s disease,
symptoms, and family variables objectively rather than using subjective thresholds for
referral.48

Provider/Patient Education
It is imperative gynecologic oncologists provide primary palliative care services to
maintain a sustainable model of palliative care. Despite these expectations, gyneco-
logic oncologists actually receive minimal formal training in this arena. Although
approximately 90% of gynecologic oncology fellows reported palliative care is integral
to their training, only 11% actually had any formal training. Those who did receive
formal training reported increased vigilance to deal with end-of-life issues.36 A total
of 77% of board-certified gynecologic oncologists stated that more training during
fellowship would have been beneficial in practice.16 In response, the SGO has
made great efforts to improve education and promote collaboration with palliative
care specialists.
Equally important is education of the public and patients regarding the role of palli-
ative care and what services are provided. Palliative care is often mistaken for end-of-
life or hospice care. Unlike end-of-life care, palliative care is delivered throughout the
duration of treatment even when there is curative intent. This incorrect stigma comes
from an often late introduction to palliative care. El-Sahwi and coworkers49 surveyed
gynecologic oncologists and noted that 53.9% deferred end-of-life discussions until
the patient has sustained a major change in functional or medical status. The term
“palliative care” was initially created as a more socially acceptable term in response
to the historical association of hospice with dying. However, palliative care has now
also become associated with end-of-life as hospice originally was.35 Education is
necessary to discredit misconceptions about the role of palliative care and the ser-
vices it has to offer to improve implementation.35 Early introduction to specialty palli-
ative care may increase rapport with providers, dispel the negative association with
end-of-life, enhance symptom control, and improve expectations.

Clinical Trials
Clinical trials provide innovative ways to increase palliative care uptake. Zander and
colleagues50 studied automatic palliative care consultation for patients with
advanced, incurable cancer. As a result, 67% of oncologists believed patient care
was improved and promoted discussion of patients end-of-life goals. Dalal and col-
leagues51 trialed a name change of palliative care to supportive care and found an as-
sociation with increased inpatient palliative care consultations and outpatient
consultation. One health care system worked with an insurance supplier to change
the model of payment; payment went from fee-for-service to pay-for-performance.
Before the change in reimbursement, palliative care quality improvement metrics
were selected including percentage of patients seen by the palliative care service
who were deemed high-risk. After the intervention palliative care consultation rates
tripled in high-risk groups.52 Specifically in gynecologic oncology patients, Mullen
and colleagues53 demonstrated that the integration of palliative care and hospice
resulted in increased hospice enrollment and increased time on hospice. Other clinical
trials conducted within this patient population suggest that an established palliative
care service well integrated into the gynecologic oncology service and with a constant
presence/availability (someone on call 24 hours a day) improves consultation
rates.10,53 Although clinical trials suggest mechanisms to improve palliative care
use, further research is necessary to understand how improved uptake of these inter-
ventions impacts all patients and practice settings.
 Palliative Care in Gynecologic Oncology 189

MANAGEMENT OF COMMON SYMPTOMS

The SGO emphasizes providing comprehensive care to gynecologic oncology pa-

tients from the time of diagnosis to death.4,54 Therefore, it is important to understand
how to manage common symptoms that patients with advanced malignancies
experience.4

Anorexia
 Address reversible causes (constipation, pain, medications, hypercalcemia,
mucositis)
 Gastrokinetic agents (metoclopramide, domperidone)
 Low-dose corticosteroids (short term)
 Progesterone agents
 Cannabinoids (dronabinol and medical marijuana)
 Counsel patients and caregivers away from meeting nutrition goals to avoid
suffering from forced feeding

Bone Metastasis
 External-beam radiation
 Opioids and analgesic nerve blocks for pain control
 Bisphosphonates (pamidronate, zoledronic acid)
 Denosumab (human monoclonal antibody to inhibit the receptor activator of
nuclear factor-kappa B to diminish maturation of osteoclasts)
 Surgery or interventional radiology (to stabilize the skeleton by vertebroplasty)

Brain Metastasis
 Consult radiation oncology and neurosurgery
 Steroids (only if symptomatic, dexamethasone orally 4–8 mg/d up to 100 mg/d for
severe symptoms)
 If plan for radiation start 48 hours before treatment to prevent severe cerebral
edema
 Whole-brain radiation (one to three lesions and widespread disease)
 Surgery (good prognosis) and/or stereotactic radiosurgery (multiple lesions,
incompletely resected single lesion)55
 Antiepileptic drugs (only for patients with seizures)

Constipation
 Rule out bowel obstruction and fecal impaction
 Initiate bowel regimen immediately with opioid use
 Stool softeners (docusate sodium)
 Osmotic agents (magnesium hydroxide, lactulose, polyethylene glycol)
 Stimulants (senna, bisacodyl)
 Lubricants (glycerin suppositories)
 Enemas (mineral oil, soap suds)
 Opioid antagonist (methylnaltrexone)

Delirium
 Discontinue all high-risk medications, regularly reorient the patient, minimize
stimulation, minimize use of restraints, encourage use of glasses/hearing aids
 Hyperactive delirium
190 Mullen et al

 Haloperidol (0.5–2 mg orally [PO]/intravenous [IV]/intramuscular [IM]/subcu-

taneous [SC] every 2–12 hours as needed) or chlorpromazine (12.5–50 mg
PO/IV/IM/SC/rectally every 4–6 hours as needed)
 Olanzapine or risperidone (patients intolerant of haloperidol)
 Lorazepam (for irreversible, hyperactive delirium)
 Hypoactive delirium
 No pharmacologic interventions have been proven to be effective

Dyspnea
First Line:
 Relaxation or distraction techniques (music, guided imagery, cognitive behavioral
therapy)
 Fan (facial cooling/air movement)
 Oxygen (even in patients without hypoxemia)
 Physiotherapy/chest wall percussion (helps mobilize secretions)
Second Line:
 Systemic opioids (opioid-naive morphine 2.5–5 mg PO every 4 hours; long-active
opioid-increased baseline by 30% and adjust breakthrough)
 Benzodiazepine (lorazepam 0.5–1 mg PO every 4 hours as needed)
 Anticholinergics (glycopyrrolate 0.2–0.4 mg SC/sublingual/PO every 4– 8 hours)
 Interventions specific to etiology (Table 1)

Hemorrhage
 Volume resuscitation (blood transfusion case-by-case basis)
 Psychological support to patient and family
 Apply pressure
 Dark towels and suction
 Consider sedatives or narcotics (midazolam 2.5–5 mg IV or SQ every 10–15
minutes as needed)

Table 1
Management of dyspnea based on etiology

Disease Process Possible Intervention

Pneumonia Antibiotics, pulmonary toilet
Lymphangitic tumor Diuretics, glucocorticoids
Pneumonitis, radiation or chemotherapy Glucocorticoids
induced
Venous thromboembolism Anticoagulation, interior vena cava filter
Pleural effusion Indwelling catheter, thoracentesis, video-
assisted thoracoscopic surgery, pleurodesis
Airway obstruction by tumor or Radiation therapy, glucocorticoids
lymphadenopathy
Bronchoconstriction (chronic obstructive Bronchodilators, glucocorticoids
pulmonary disease, asthma)
Retained or excess secretions Anticholinergic agents
Massive ascites Drainage, including indwelling catheter
Anxiety, including hyperventilation Anxiolytics, cognitive behavioral therapy

From Landrum LM, Blank S, Chen LM, et al. Comprehensive care in gynecologic oncology: the
importance of palliative care. Gynecol Oncol 2015;137(2):194; with permission.
 Palliative Care in Gynecologic Oncology 191

 Genitourinary
 Packing (vaginal hemorrhage)
 Bladder irrigation (bladder hemorrhage)
- Cystoscopic coagulation > infusion of 1% alum

- Administration of prostaglandin E2 and silver nitrate

- Formalin

 External-beam radiotherapy (hypofractionation, 2 fractions over 2–3 days)

 Arterial embolization by interventional radiology
 Gastrointestinal
 Endoscopy
 Surgical ligation or clipping of bleeding vessels

Hypercalcemia (Adjusted Total Serum Calcium >10.2)

 Hydration with intravenous normal saline
 Bisphosphonates (pamidronate or zoledronic acid)
 Addition of calcitonin in patients with severe hypercalcemia

Intractable Symptoms at End of Life

 Palliative care consultation recommended
 Family meeting to verify goals of care/discuss sedation
 Midazolam, methotrimeprazine, propofol, phenobarbital

Malignant Ascites
 Maximize diuretics to decrease albumin loss
 Furosemide (40–80 mg IV/PO twice a day) and spironolactone (50–200 mg PO
twice a day)
 Paracentesis (immediate symptom relief)
 Permanent drains

Malignant Bowel Obstruction (Nonoperable)

 Conservative management with nasogastric tube
 Intravenous fluids
 Partial bowel obstruction
 Prokinetic agent, metoclopramide
 Steroid, dexamethasone
 Antiemetic, haloperidol
 Antispasmodic, hyoscine butylbromide
 Complete bowel obstruction
 Avoid prokinetic agent if increased cramping/pain
 Steroid, dexamethasone
 Antiemetic, haloperidol
 Octreotide to decrease secretions
 Consider gastrostomy tube
 Total parenteral nutrition (ONLY if possibility of surgery in the future)

Nausea/Vomiting
 Use optimal dosing/route (Table 2)
 Scheduled dosing
 Maximize primary agent and then add secondary (do not switch agents)
 Avoid drugs with similar toxicities (reduces side effects)
 192
Table 2
Antiemetic agents, dosing, and adverse effects

Mullen et al
Class Drug Principal Action Route Dose Frequency Major Adverse Events
Dopamine Chlorpromazine CTZ/vomiting center PO/IM/IV 625 mg Q8h Dystonia, akathisia, sedation, postural
antagonist hypotension
Prochlorperazine CTZ PO 50–10 mg Q 4–6 h Dystonia, akathisia, sedation
PR 25 mg
IM/IV 10–20 mg Q 3–6 h
Metoclopramide CTZ/GI cholinergic PO/IV 10–20 mg Q 2–4 h Dystonia, akathisia, esophageal spasm,
colic
Haloperidol CTZ PO/IV 0.5–1 mg Q8h Dystonia and akathisia, anticholinergic,
sedation
Anticholinergic Scopolamine Vestibular, vomiting center Transdermal 1.5 mg Q3d Dry mouth, blurred vision, ileus, urinary
retention, confusion
Hydroxyzine Periphery, GI tract PO 6.25–25 mg QHS Dry mouth, sedation, dystonia
H1 antihistamine Diphenhydramine Vomiting center PO 50–75 mg Q 4–6 h Sedation, dry mouth, urinary retention
IV/IM 25–50 mg
Promethazine Upper GI tract, vomiting center PO/IM 12.5–25 mg Q8h Dystonia, akathisia, sedation
5-HT3 antagonist Ondansetron Upper GI tract, CNS PO/IV/SL 4–8 mg Q 4–8 h Headache, fatigue, constipation
Dolasetron PO 100 mg Q 24 h
Granisetron PO 2 mg PO Q 24 h
Palonosetron IV 0.01 mg/kg 1 mg Q 24 h
Transdermal 3.1 mg 24 h Q7d
IV 0.25 mg Q 24 h
Steroids Dexamethasone Not known PO/IV 4–24 mg Q morning Hyperglycemia, headache, oral
candidiasis, peptic ulcer, insomnia,
anxiety, psychosis
Cannabinoids Dronabinol Vomiting center PO 7.5–15 mg Q 3–4 h Sedation, anticholinergic euphoria,
dysphoria, tachycardia
Benzodiazepine Lorazepam Not known IV, PO 0.5–2 mg Q4h Mild sedation, amnesia, confusion (avoid
in elderly)

Abbreviations: CNS, central nervous system; CTZ, chemoreceptor trigger zone; GI, gastrointestinal; IM, intramuscular; IV, intravenous; PO, per os; PR, per rectum;
SL, sublingual.
From Landrum LM, Blank S, Chen LM, et al. Comprehensive care in gynecologic oncology: the importance of palliative care. Gynecol Oncol 2015;137(2):196; with
permission.
 Table 3
Adjuvant pain medications

Class Drug Principal Action Route Starting Dose Frequency Major Adverse Events
Steroids Dexamethasone Inhibit prostaglandin synthesis PO 1–2 mg QD or BID Hyperglycemia
Headache
Oral candidiasis
Prednisone Decrease inflammation PO 7.5–10 mg QD Insomnia
Anxiety
Psychosis
Antidepressants Desipramine Tricyclic antidepressants, PO 10–25 mg QHS Prolong QTc interval
inhibit norepinephrine Sexual dysfunction
reuptake Anticholinergic effects
Nortriptyline PO 10–25 mg (may increase to QHS Lower seizure threshold
50–150 mg QHS)
Venlafaxine Serotonin-norepinephrine PO 37.5 mg (may increase up to QD Nausea
reuptake inhibitor 37.5–112.5 mg BID) Sexual dysfunction

Palliative Care in Gynecologic Oncology

Somnolence
Hypertension
Duloxetine PO 30 mg (may increase up to QD
60 mg)
Anticonvulsants Gabapentin Inhibit depolanzation of PO 100–300 mg (may increase up QHS Dizziness
neurons to 900–3600 mg in BID-TID Somnolence
doses)
Pregabalin PO 50 mg (may increase to 100 mg TID Mental cloudiness
TID)
Bisphosphonates Pamidronate Osteoclast inhibitors IV 60 mg Q month Renal impairment
Zoledronic acid IV 4 mg Q 21 d Flulike syndrome with
initiation of treatment

From Landrum LM, Blank S, Chen LM, et al. Comprehensive care in gynecologic oncology: the importance of palliative care. Gynecol Oncol 2015;137(2):199; with
permission.

193
194 Mullen et al

Pain Management
 Per the WHO analgesic ladder for pain management pain should be treated in a
stepwise fashion first using nonopioids plus or minus adjunctive analgesics fol-
lowed by opioid combinations including nonopioids and adjunctive analgesics
(Table 3)56
 Long-active opioid and short-acting opioid for breakthrough pain if necessary
 Dosage of long-acting opioid is based on 24-hour needs
 Breakthrough is w10% of 24-hour opioid dose
 Rotate opioid if unmanageable side effects
 Regularly monitor for opioid toxicity specifically in patients with renal dysfunction
 If pain decreased because of treatment, gradually decrease opioids to avoid
oversedation
 Nonsteroidal anti-inflammatory drugs
 Neuraxial blocks

SUMMARY

The integration of palliative care into standard gynecologic care is undoubtedly asso-
ciated with improved patient outcomes, enhanced quality of life, and financial benefits.
As a result, it is strongly endorsed by the NCCN, ASCO, and SGO. However, use of
these services by gynecologic oncology patients continues to be disappointing and
to occur too late in the disease process to obtain maximum benefit. To optimize
end-of-life care for patients, oncologists and palliative care providers must collaborate
to concurrently provide palliative care and anticancer treatment throughout the
disease course. Further research is necessary to identify interventions to increase
hospice and palliative care uptake, to implement palliative care earlier in a patient’s
oncologic care, and to eliminate disparities.

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