Although research has shown that palliative chemotherapy is beneficial compared to lack of treatment (Schorge JO, Schaffer JI, Halvorson LM, et al. ed. Williams Gynecology. New York, NY: McGraw Hill Medical; 2008.), other studies show aggressive end-of-life treatment adversely affects quality of life and shortens life span (Arriba L, Fader A, Frasure H, von Gruenigen V. A review of issues surrounding quality of life among women with ovarian cancer. Gynecol Oncol. 2010;119(2):390-396.). Without a consensus on palliative chemotherapy, underutilization during end of life prevails, and likely will continue without additional research (Barbera L, Elit L, Krzyzanowska M, et al. End of life care for women with gynecologic cancers. Gynecol Oncol. 2010;118(2):196-201.). This article aims to evaluate and examine existing chemotherapy for palliation of malignant ascites secondary to ovarian cancer and compare commonly used regimens. Agents will be evaluated by their modes of administration. Oral agents include cyclophosphamide and thalidomide, and intraperitoneal vehicles include taxane-based agents, platinum-based agents, antibiotics, and biologic agents. In addition, cost, ethics, and quality of life discussions factor into this review. Palliative care’s goal is to find a balance between life expectancy and symptom relief with minimal adverse effects.
SchorgeJOSchafferJIHalvorsonLM. ed. Williams Gynecology. New York, NY: McGraw Hill Medical; 2008.
2.
JelovacDArmstrongDK. Recent progress in the diagnosis and treatment of ovarian cancer. A Cancer J Clin. 2011;61(3):183–203.
3.
ArribaLFaderAFrasureHvon GruenigenV. A review of issues surrounding quality of life among women with ovarian cancer. Gynecol Oncol. 2010;119(2):390–396.
4.
VergoteITropeCGAmantF. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010;363(10):943–953.
5.
GoffBAMandelLSMelanconCHMuntzHG. Frequency of symptoms of ovarian cancer in women presenting to primary care clinics. JAMA. 2004;291(22):2705–2712.
6.
BuysSSPartridgeEBlackA. Effect of screening on ovarian cancer mortality-the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening randomized controlled trial. JAMA. 2011;305(22):2295–2303.
7.
YedemaCAKenemansPWobbesT. Use of serum tumor markers in the differential diagnosis between ovarian and colorectal adenocarcinomas [Abstract]. Tumour Biol. 1992;13(1-2):18–26.
8.
McGuireWPHoskinsWJBradyMF. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med. 1996;334(1):1–6.
9.
SamaritaniRCorradoGVizzaESbiroliC. Cyclophosphamide “metronomic” chemotherapy for palliative treatment of a young patient with advanced epithelial ovarian cancer. BMC Central. 2007;7:65.
10.
HoskinsPJLeN. Identifying patients unlikely to benefit from further chemotherapy: a descriptive study of outcome at each relapse in ovarian cancer. Gynecol Oncol. 2005;97(3):862–869.
11.
JemalASiegelRWardE. Cancer statistics. CA Cancer J Clin. 2009;59(4):225–249.
12.
HarringtonSESmithTJ. The role of chemotherapy at the end of life: “When is enough, enough?”JAMA. 2008;299(22):2667–2678.
13.
AlbertsDSLiuPYHanniganEV. Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med. 1996;335(26):1950–1955.
14.
ArmstrongDKBundyBWenzelL. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006;354(1):34–43.
15.
HavrileskyLJSecordAADarcyKMKulasingamS. Cost effectiveness of intraperitoneal compared with intravenous chemotherapy for women with optimally resected stage III ovarian cancer: a gynecologic oncology group study. J Clin Oncol. 2008;26(25):4144–4150.
16.
PattenSGAdamcicULacombeKMinhasKSkowronskiKCoomberBL. VEGFR2 heterogeneity and response to anti-angiogenic low dose metronomic cyclophosphamide treatment. BMC Cancer. 2010;10:683–693.
17.
DedrickRLMyersCEBungayPMDeVitaVT JR. Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer [abstract]. Cancer Treat Rep. 1978;62(1):1–11.
18.
ChaudharyKHaddadinSMNistalaRPapageorgioC. Intraperitoneal drug therapy: an advantage [abstract]. Current Clin Pharmacol. 2010;5(2):82–88.
19.
RosenbergSM. Palliation of malignant ascites. Gastroenterol Clin North Am. 2006;35(1):189xi–199xi.
20.
MishraK. Gynaecological malignancies from palliative care perspective. Indian J Palliat Care. 2011;17(suppl):S45–S51.
21.
BaronTH. Expandable Metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med. 2001;344(22):1681–1687.
CellaDFTulskyDSGrayG. The functional assessment of cancer therapy scale: development and validation of the general measure [abstract]. J Clin Oncol. 1993;11(3):570–579.
24.
von GruenigenVEHutchinsJRReidyAM. Gynecologic oncology patients’ satisfaction and symptom severity during palliative chemotherapy. Health and Quality of Life Outcomes. 2006;4:84.
25.
PensonRTDignanFSeidenMV. Attitudes to chemotherapy in patients with ovarian cancer. Gynecol Oncol. 2004;94(2):427–435.
26.
BarberaLElitLKrzyzanowskaM. End of life care for women with gynecologic cancers. Gynecol Oncol. 2010;118(2):196–201.
27.
DoyleCCrumpMPintilieMOzaA. Does palliative chemotherapy palliate? Evaluation of expectations, outcomes, and costs in women receiving chemotherapy for advanced ovarian cancer. J Clin Oncol. 2001;19(5):1266–1274.
28.
Von GruenigenVEDalyBJ. Futility: clinical decisions at the end of life in women with ovarian cancer. Gynecol Oncol. 2005;97(2):638–644.
29.
WanGJCounteMACellaDF. The influence of personal expectations on cancer patients’ reports of health related quality of life. Psycho-oncology. 1997;6(1):1–11.
30.
SlevinMLStubbeLPlantHJ: Attitudes to chemotherapy: comparing views of patients with cancer with those of doctors, nurses and general public. BMJ. 1990;300(6737):1458–1460.
31.
DonovanKAGreenePGShusterJLPartridgeEETuckerDC. Treatment preferences in recurrent ovarian cancer. Gynecol Oncol. 2002;86(2):200–211.
32.
Von GuntenCF. Secondary and tertiary palliative care in US hospitals. JAMA. 2002;287(7):875–881.
33.
McCartneyCFLarsonDB. Quality of life in patients with gynecologic cancer. Cancer. 1987;60(8 suppl):2129–2136.
34.
LevyMHBackAMBenedettiC. NCCN clinical practice guidelines in oncology: palliative care [abstract]. J Natl Compr Cancer Netw. 2009;7(4):436–473.
35.
KeyserEAReedBLoweryW. Hospice enrollment for terminally ill patients with gynecologic malignancies: Impact on outcomes and interventions. Gynecol Oncol. 2010;118(3):274–277.
36.
DoyleCStocklerMPintilieM. Resource implications of palliative chemotherapy for ovarian cancer [abstract]. J Clin Oncol. 1997;15(3):1000–1007.
37.
LewinSNButtinBMPowellMA. Resource utilization for ovarian cancer patients at the end of life: how much is too much?Gynecol Oncol. 2005;99(2):261–266.
38.
SistiguAVilaudSChaputN. Immunomodulatory effects of cyclophosphamide and implementations for vaccine design [Abstract]. Seminars in Immunopathology. 2011;33(4):369–383.
39.
GaspariniG. Metronomic scheduling: the future of chemotherapy?Lancet oncol. 2001;2(12):733–740.
40.
WatanabeYEtohTKoikeE. Feasibility study of oral cyclophosphamide salvage therapy for the treatment of heavily pretreated patients with recurrent epithelial ovarian cancer. Int J Clin Oncol. 2010;15(5):468–471.
41.
D’AmatoRJLoughnanMSFlynnEFolkmanJ. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci. 1994;91(9):4082–4085.
42.
GordinierMEDizonDSWeitzenS. Oral Thalidomide as palliative chemotherapy in women with advanced ovarian cancer. J Palliat Med. 2007;10(1):61–66.
43.
ChanJKManuelMRCiaravinoGCheungMKHusainATengNN. Safety and efficacy of thalidomide in recurrent epithelial ovarian and peritoneal carcinoma. Gynecol Oncol. 2006;103(3):919–923.
44.
ButtinBMMooreMJ. Thalidomide-induced reversible interstitial pneumonitis in a patient with recurrent ovarian cancer. Gynecol Oncol. 2008;111(3):546–548.
45.
IkhlaqueNSeshadriVKathulaSBaumannMA. Efficacy of prophylactic warfarin for prevention of thalidomide related deep venous thrombosis. Am J Hematol. 2006;81(6):420–422.
46.
DownsLSJudsonPLArgentaPA. A prospective randomized trial of thalidomide with topotecan compared with topotecan alone in women with recurrent epithelial ovarian carcinoma. Cancer. 2008;112(2):331–339.
47.
ClementsMJonesCCummingMDaoudSS. Antiangiogenic potential of captothenic and topotecan. Cancer Chemother Pharmacol. 1999;44(5):411–416.
48.
ArmstrongDK. Topotecan dosing guidelines in ovarian cancer: reduction and management of hematologic toxicity. Oncologist. 2004;9(1):33–42.
49.
McGuireWPBlessingJABookmanMALentzSSDuntonCJ. Topotecan has substantial antitumor activity as first line salvage therapy in platinum sensitive epithelial ovarian carcinoma: a gynecologic oncology group study. J Clin Oncol. 2000;18(5):1062–1067.
50.
SwisherEMMutchDGRaderJSElbendaryAHerzogTJ. Topotecan in platinum-and paclitaxel-resistant ovarian cancer. Gynecol Oncol. 1997;66(3):480–486.
51.
MabuchiSOhmichiMKimuraA. Tamoxifen inhibits cell proliferation via mitogen activated protein kinase cascades in human ovarian cancer cell lines in a manner not dependent on the expression of estrogen receptors or the sensitivity to cisplatin. Endocrinology. 2004;145(3):1302–1313.
52.
HurteauJABradyMFDarcyKM. Randomized phase III trial of tamoxifen versus thalidomide in women with biochemical-recurrent-only epithelial ovarian, fallopian tube or primary peritoneal carcinoma after a complete response to first-line platinum/taxane chemotherapy with an evaluation of serum vascular endothelial growth factor (VEGF): a gynecologic oncology group study. Gynecol Oncol. 2010;199(3):444–450.
53.
HatchKDBeechamJBBlessingJACreasmanWT. Responsiveness of patients with advanced ovarian carcinoma to tamoxifen, a gynecologic oncology group study of second-line therapy in 105 patients. Cancer. 1991;68(2):269–271.
54.
MarkmanMIsemingerKAHatchKDCreasmanWTBarnesWDubeshterB. Tamoxifen in platinum refractory ovarian cancer: a gynecologic oncology group ancillary report. Gynecol Oncol. 1996;62(1):4–6.
55.
YanTDCaoCQMunkholm-LarsenS. A pharmacological review on intraperitoneal chemotherapy for peritoneal malignancy. World J Gastrointest Oncol. 2010;2(2):109–116.
56.
LosGMutsaersPHLengletWJBaldewGSMcVieJG. Platinum distribution intraperitoneal tumors after intraperitoneal cisplatin treatment [abstract]. Cancer Chemother Pharmacol. 1990;25(6):389–394.
57.
HowellSBPfeifleCLWungWE. Intraperitoneal cisplatin with systemic thiosulfate protection. Ann Intern Med. 1982;97(6):845–851.
58.
LeTLatifahHJolicouerJ. Does intraperitoneal chemotherapy benefit optimally debulked epithelial ovarian cancer patients after neoadjuvant chemotherapy?Gynecol Oncol. 2011;121(3):451–454.
59.
KrasnerCNRocheMHorowitzNSSupkoJGLeeSIOlivaE. Case 11-2006: a 54-year old woman with a mass in the pelvis. N Engl J Med. 2006;354(15):1615–1625.
60.
BarakatRSabbatiniPBhaskaranD. Intraperitoneal chemotherapy for ovarian carcinoma: results of long-term follow-up in 411 patients. J Clin Oncol. 2002;20(3):694–698.
61.
WenzelLBHuangHQArmstrongDK. Gynecologic oncology group. Health related quality of life during and after intraperitoneal versus intravenous chemotherapy for optimally debulked ovarian cancer: a gynecologic oncology group study. J Clin Oncol. 2007;25(4):437–443.
62.
MarkmanM. Intraperitoneal antineoplastic drug delivery: rationale and results. Lancet. 2003;4(5):277–283.
63.
TanyiJLMcCannGHagemannAR. Clinical predictors of bevacizumab-associated gastrointestinal perforation. Gynecol Oncol. 2011;120(3):464–469.
64.
EskanderRNRandallLM. Bevacizumab in the treatment of ovarian cancer. Biologics: Targets and Therapy. 2011;5:1–5.
65.
KuhHJJangSHWientjesMG. Determinants of paclitaxel penetration and accumulation in human solid tumor. J Pharmacol Exp Ther. 1999;290(2):871–880.
66.
YoungRCBradyMFNiebergRK. Adjuvant treatment for early ovarian cancer: a randomized phase III trial of intraperitoneal 32P or intravenous cyclophosphamide and cisplatin–a gynecologic oncology group study. J Clin Oncol. 2003;21(23):4350–4355.
67.
GordonANFleagleJTGuthrieDParkinDEGoreMELacaveAJ. Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol. 2001;19(14):3312–3322.
68.
GordonANGranaiCORoseP. Phase II study of liposomal doxorubicin in platinum and paclitaxel refractory epithelial ovarian cancer. J Clin Oncol. 2000;18(17):3093–3100.
NumnumTMRocconiRPWhitworthJ. The use of bevacizumab to palliate symptomatic ascites in patients with refractory ovarian carcinoma. Gynecol Oncol. 2006;102(3):425–428.
71.
HamiltonCAMaxwellGLChernofskyMRBernsteinSAFarleyJHRoseGS. Intraperitoneal bevacizumab for palliation of malignant ascites in refractory ovarian cancer. Gynecol Oncol. 2008;111(3):530–532.
