Palliative Care Issues in Gynecologic Cancer

Rachel Regn, MD

Ob/Gyn Resident, Postgraduate Year 2

William-Robinson, MD

Maxwell E Lapham Professor

of Gynecologic Oncology

Tulane Cancer Center

Tulane University School of Medicine

The goal of palliative care (PC) is to treat/prevent the noxious effects of cancer via a holistic approach. PC is multifaceted, requiring a cross-disciplinary team equipped to address physical, psychological, social, and spiritual problems. PC does not preclude curative therapies, and multiple reports have shown that it improves quality of life, reduces costs, and does not shorten survival.^1,2 PC is of particular importance in gynecologic cancer. Treatment may require surgery, chemotherapy, radiation therapy or (increasingly) all three modalities. Surgery is often complex, extensive, and includes risks of bleeding, infection, and thrombophlebitis.

Chemotherapy requires intravenous and intraperitoneal infusion of multiple cytotoxic agents. Radiation therapy makes frequent use of painful and debilitating intracavitary applications. Gynecologic cancer disproportionately affects families, as well. Commonly striking mid-life women, gynecologic cancer frequently damages familial cohesion. Low-income communities with numerous matriarchal families suffer particularly devastating consequences from the loss of a mother.

PC issues particularly associated with gynecologic cancer include: lower extremity lymphedema (LEL), sexual function problems, chemotherapy-induced peripheral neuropathy (CIPN), and post-chemotherapy cognitive dysfunction (“chemobrain”).

LEL occurs following pelvic lymphadenectomy and is typically worsened by subsequent radiation. Although the precise incidence, risk factors, and severity are not well defined, in its extreme form, LEL can be crippling. Treatments include lymphatic massage, fitted garments, and mechanical compression. LEL is more easily prevented than reversed, so early intervention is important.³ Current trials will improve understanding of LEL within the next few years.

Sexual function changes can contribute to stress, depression, and anxiety and may have profound effects on quality of life, relationships, and personal identity. Female sexual function can deteriorate, often dramatically, during menopause, and iatrogenic menopause is often a part of gynecologic cancer therapy. Surgical oophorectomy is commonly performed. Standard pelvic radiation therapy and multiagent chemotherapy typically cause ovarian failure, as well. Characterized by decreased estrogen production, ovarian failure can cause poor vaginal lubrication/elongation, altered genital sensitivity, and decreased libido.

Treatment options are limited. Estrogen replacement is contraindicated for endometrial and some other cancers. Pharmacologic alternatives include the antihypertensive agent clonidine and the serotonin inhibitor venlafaxine.⁴ Nonpharmacologics, including acupuncture and yoga, may be effective.⁵

CIPN is strongly associated with cisplatin and paclitaxel, commonly used agents in gynecologic cancer. Further, patients may receive multiple chemotherapy regimens lasting 6 months or longer, often with repeated use of the same agents. CIPN progresses proximally with a cumulative, dose-related effect that is often difficult to measure objectively.

Most cases resolve, but some may be persistent. ⁶ Gabapentin, venlafaxine and analgesics are commonly used, but no consistent, standard treatment has been identified.⁷ Amifostine has been studied in ovarian cancer, but proved to be unacceptable to patients, as it required tri-weekly IV administration, supine positioning, prophylactic antiemetics, and resuscitation capability.⁸

Chemobrain includes changes in memory, fluency, motor coordination, and calculations, and may occur in 40% of patients. First described in 1997, chemobrain has been reported in multiple cancer types.⁹

A recent study of chemobrain in ovarian cancer evaluated processing speed, reaction time, and attention/ memory. Over 30% had a decline in at least one area, most commonly attention/memory, although depression and anxiety may be confounders.¹⁰ Interventional trials are in development for this population.

In summary, PC should address the unique symptom profile of gynecologic cancer and be tailored to individual socioeconomic environments. Benefits from PC innovations in gynecologic cancer may exceed those of traditional therapies.

References

• Bakitas MA, Tosteson TD, Li Z, et al. Early versus delayed initiation of concurrent palliative oncology care: patient outcomes in the ENABLE III randomized controlled trial. J Clin Oncol. 2015;33(13):1438-1445.
• Taplin SH, Weaver S, Salas E, et al. Reviewing cancer care team effectiveness. J Oncol Pract. 2015;11(3):239-246.
• Hareyama H, Hada K, Goto K, et al. Prevalence, classification, and risk factors for postoperative lower extremity lymphedema in women with gynecologic malignancies: a retrospective study. Int J Gynecol Cancer. 2015;25(4):751-757.
• L’Espérance S, Frenette S, Dionne A, et al. Pharmacological and non-hormonal treatment of hot flashes in breast cancer survivors: CEPO review and recommendations. Support Care Cancer. 2013;21(5):1461-1474.
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• Beijers A, Mols F, Dercksen W, et al. Chemotherapy-induced peripheral neuropathy and impact on quality of life 6 months after treatment with chemotherapy. J Community Support Oncol. 2014;12(11):401-406.
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• Moore DH, Donnelly J, McGuire WP, et al. Limited access trial using amifostine for protection against cisplatin- and three-hour paclitaxel-induced neurotoxicity: a phase II study of the Gynecologic Oncology Group. J Clin Oncol. 2003;21(22):4207-4213.
• Tannock IF, Ahles TA, Ganz PA, et al. Cognitive impairment associated with chemotherapy for cancer: report of a workshop. J Clin Oncol. 2004;22(11):2233-2239.
• Hess L, Huang H, Robinson W, et al. Cognitive function during chemotherapy for front-line treatment of ovarian, primary peritoneal or fallopian tube cancer: a Gynecologic Oncology Group study. Gynecol Tulane Cancer Center at Tulane University School of Medicine Oncol. 2013;130(1):6-7.