eMedicine Specialties > Obstetrics and Gynecology > none

Ovarian Cancer: Treatment & Medication

Author: Agustin A Garcia, MD, Associate Professor of Medicine, University of Southern California Keck School of Medicine
Contributor Information and Disclosures

Updated: Dec 13, 2007

Treatment

Medical Care

The standard treatment for ovarian cancer starts with staging and cytoreductive surgery. Based on the surgical staging, patients are classified as having limited disease (stage I and II) or advanced disease (stage III and IV).

  • Patients with limited disease are classified as having low or high risk for recurrence as follows:
    • Low risk for recurrence includes the following:
      • Grade 1 or 2 disease
      • No tumor on external surface of the ovary
      • Negative peritoneal cytology
      • No ascites
      • Tumor growth confined to the ovaries
    • High risk for recurrence includes the following:
      • Grade 3 disease
      • Preoperative rupture of the capsule
      • Tumor on the external surface of the ovary
      • Positive peritoneal cytology
      • Ascites
      • Tumor growth outside of the ovary
      • Clear cell tumors
      • Surgical stage II
  • For postoperative treatment, chemotherapy is indicated in all patients with ovarian cancer except those patients with surgical-pathological stage I disease with low-risk characteristics.
  • For female patients with carcinomatosis of an unknown primary tumor, consider the following:
    • Frequently, female patients present with carcinomatosis without an obvious pelvic mass. In many patients, an extensive search for a GI tumor fails to identify the primary tumor.
    • Consider treating these patients as having a presumed ovarian carcinoma or primary peritoneal carcinoma. Treat with cytoreductive surgery followed by platinum-based chemotherapy.

Surgical Care

The standard care for ovarian cancer includes a primary staging and cytoreductive or debulking surgical exploration.

  • Surgical staging
    • If the disease appears to be confined to the pelvis, comprehensive surgical staging is indicated.
    • The staging procedure should include (1) peritoneal cytology, (2) multiple peritoneal biopsies, (3) omentectomy, and (4) pelvic and para-aortic lymph node sampling.
  • Cytoreductive surgery
    • This should be performed by a gynecological oncologist at the time of initial laparotomy.
    • The volume of residual disease at the completion of surgery represents one of the most powerful prognostic factors.
  • Prognosis of patients after cytoreductive surgery: Patients with advanced ovarian cancer are classified in 3 groups as follows, based on the postoperative residual tumor:
    • Good risk - Microscopic disease outside the pelvis (stage IIIa) or macroscopic disease less than 2 cm outside the pelvis (stage IIIb)
    • Intermediate risk - Macroscopic disease less than 2 cm outside the pelvis only after surgery
    • Poor risk - Macroscopic disease more than 2 cm after surgery or disease outside the peritoneal cavity
  • Interval debulking
    • This can be performed in patients who were not adequately debulked at the time of initial surgery.
    • Patients receive 3 cycles of postoperative chemotherapy. Approximately 60% of patients are then able to undergo optimal resection. Surgical treatment is followed by 3 more cycles of chemotherapy.
    • A European prospective, randomized, clinical trial demonstrated that this approach improves the outcome of patients with advanced ovarian cancer. However, this was not confirmed in a study conducted in the United States. A major difference between both studies was the extent of the initial debulking procedure. In the latter study, initial optimal debulking was attempted in all patients.
    • Interval debulking surgery may be considered in those patients in whom an initial debulking surgery was not attempted.

Consultations

  • Consult a gynecologic oncologist if ovarian cancer is suspected.

Medication

Chemotherapy regimens: Standard postoperative chemotherapy is combination therapy with platinum and paclitaxel. Cisplatin and paclitaxel or carboplatin and paclitaxel are accepted alternatives. Randomized studies have proven that both regimens result in equivalent survival rates. However, because of a more tolerable toxicity profile, the combination of carboplatin and paclitaxel is preferred. If patients are treated with cisplatin, then paclitaxel should be administered as a 24-hour infusion to decrease the risk of neurotoxicity. Another alternative is to combine carboplatin with docetaxel.

Intraperitoneal chemotherapy: Results from 3 randomized clinical trials suggest that in patients with optimally debulked disease, intraperitoneal administration of chemotherapy (cisplatin) is superior to intravenous administration. Three recent meta-analyses confirm that intraperitoneal administration of chemotherapy is associated with an improvement in survival.1,2,3 However, this approach is also associated with more toxicity. The National Cancer Institute released a clinical announcement supporting the use of intraperitoneal chemotherapy in optimally debulked ovarian cancer.

Neoadjuvant chemotherapy: Patients with advanced ovarian cancer who are not candidates for surgical cytoreduction may be treated initially with 2-3 cycles of conventional chemotherapy and then be re-evaluated for surgical cytoreduction. However, optimal initial cytoreduction remains the standard of care for most patients.

Maintenance chemotherapy: Most patients with ovarian cancer achieve a complete clinical response after debulking surgery and platinum-based chemotherapy. However, 50% of them relapse and ultimately die from the disease. Therefore, strategies to decrease the risk of recurrence have been investigated. A phase III randomized trial reported an improvement in disease-free survival (DFS) when patients were treated with 12 cycles of maintenance paclitaxel.

Second-line chemotherapy: Most patients with ovarian cancer have a recurrence. Based on the disease-free interval after completing chemotherapy, patients can be classified in 2 categories: (1) platinum-sensitive (relapse >6 mo after initial chemotherapy) and (2) platinum-resistant. Patients with platinum-sensitive disease may exhibit a good response if rechallenged with a platinum-based regiment. The probability of response increases with the duration of the disease-free interval.

Results from clinical trials suggest that combination chemotherapy offers an improvement in response rate, progression-free survival, and overall survival. Several chemotherapy agents elicit a response in patients whose disease is resistant to platinum-based therapies. These include liposomal doxorubicin, topotecan, oral etoposide, gemcitabine, docetaxel, and vinorelbine. Other agents that may be used are ifosfamide, 5-fluorouracil with leucovorin, and altretamine (Hexalen). Tamoxifen, an oral antiestrogen, also exhibits modest activity but has a favorable toxicity profile.

Chemotherapy agents

Cisplatin, carboplatin, and paclitaxel are chemotherapy agents approved for the initial treatment of ovarian cancer. Results from randomized studies have shown that platinum-containing regimens are superior to those that do not contain platinum. In addition, the combination of platinum and paclitaxel is superior to a regimen that does not include paclitaxel.


Cisplatin (Platinol)

Intrastrand cross-linking of DNA and inhibition of DNA precursors are among proposed mechanisms of action.

Adult

60-100 mg/m2 IV q3wk

Pediatric

Not established

Increases toxicity of bleomycin and ethacrynic acid

Documented hypersensitivity, preexisting renal insufficiency, myelosuppression, and hearing impairment

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Can cause potassium- and magnesium-wasting nephropathy (IV hydration is used to decrease risk); frequency and severity of peripheral neuropathy are increased if cisplatin is combined with short infusions of paclitaxel; highly emetogenic (aggressive antiemetic prophylaxis with a selective serotonin antagonist and steroids recommended); produces modest myelosuppression


Carboplatin (Paraplatin)

Analog of cisplatin. Has same efficacy as cisplatin but with better toxicity profile.
Dose is based on the following formula: total dose (mg) = (target AUC) X (GFR = 25) where AUC (area under plasma concentration-time curve) is expressed in mg/mL/min and GFR (glomerular filtration rate) is expressed in mL/min.

Adult

Target AUC of 4-7.5 IV q3-4wk recommended

Pediatric

Not established

Nephrotoxicity increases with aminoglycosides and other nephrotoxic drugs

Documented hypersensitivity; bone marrow suppression

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Produces significantly less nephrotoxicity, peripheral neuropathy, nausea, and vomiting compared to cisplatin; IV hydration not required; produces more myelosuppression than cisplatin


Paclitaxel (Taxol)

Mechanism of action is tubulin polymerization and microtubule stabilization.

Adult

175 mg/m2 as 3-h IV infusion q3wk; alternatively, 135 mg/m2 as 24-h IV infusion q3wk

Pediatric

Not established

Coadministration with cisplatin may further increase myelosuppression

Documented hypersensitivity to paclitaxel or polyoxyethylated castor oil; peripheral neuropathy; bone marrow suppression; severe cardiac disease

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Patients should be premedicated with steroids and H1 and H2 blockers to decrease risk of hypersensitivity reactions; other adverse effects include myelosuppression, alopecia, peripheral neuropathy, myalgias/arthralgias, and cardiac arrhythmia


Liposomal doxorubicin (Doxil)

Interferes with synthesis of nucleic acid by intercalating with DNA nucleotide pairs and topoisomerase II inhibition.

Adult

40-50 mg/m2 IV q4wk

Pediatric

Not established

May decrease phenytoin and digoxin plasma levels; phenobarbital may decrease plasma levels; cyclosporine may induce coma or seizures; mercaptopurine increases toxicity; cyclophosphamide increases cardiac toxicity

Documented hypersensitivity; severe heart failure, cardiomyopathy, impaired cardiac function, preexisting myelosuppression; impaired liver function

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Irreversible cardiac toxicity and myelosuppression may occur; extravasation may result in severe local tissue necrosis; reduce dose in patients with impaired hepatic function; adverse effects include infusion reactions, mucositis, and skin toxicity (palmar-plantar erythrodysesthesia); nausea and vomiting are mild; alopecia and cardiac toxicity are uncommon

Antineoplastic Agents

These agents inhibit cell growth and proliferation.


Topotecan (Hycamtin)

Inhibits topoisomerase I, inhibiting DNA replication. Patients who have received prior chemotherapy should be given a lower dose initially.

Adult

1.5 mg/m2/d IV for 5 d q4wk

Pediatric

Not established

Concomitant administration with other antineoplastics may result in prolonged neutropenia and thrombocytopenia in addition to increased morbidity/mortality

Documented hypersensitivity; bone marrow suppression and renal function impairment

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Adverse effects include myelosuppression, dermatitis, nausea, and vomiting; monitor bone marrow function


Gemcitabine (Gemzar)

Cytidine analog. Metabolized intracellularly to active nucleotide. Inhibits ribonucleotide reductase and competes with deoxycytidine triphosphate for incorporation into DNA. Cell-cycle specific for S phase. Indicated for advanced ovarian cancer (that has relapsed at least 6-months after completion of platinum-based therapy. Used in combination with carboplatin.

Adult

1000 mg/m2 IV infused over 30 min on days 1 and 8 of each 21-day cycle; administer carboplatin on day 1 after gemcitabine

Pediatric

Not established

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May cause myelosuppression (particularly thrombocytopenia); toxicities include flu like syndrome, LFT abnormality, maculopapular rash, pruritus, nausea, vomiting, dyspnea, hematuria, proteinuria, and hemolytic uremic syndrome; clearance reduced in women and elderly individuals

More on Ovarian Cancer

Overview: Ovarian Cancer
Differential Diagnoses & Workup: Ovarian Cancer
Treatment & Medication: Ovarian Cancer
Follow-up: Ovarian Cancer
References
[ CLOSE WINDOW ]

References

  1. Hess LM, Benham-Hutchins M, Herzog TJ, Hsu CH, Malone DC, Skrepnek GH. A meta-analysis of the efficacy of intraperitoneal cisplatin for the front-line treatment of ovarian cancer. Int J Gynecol Cancer. May-Jun 2007;17(3):561-70. [Medline].

  2. Elit L, Oliver TK, Covens A, Kwon J, Fung MF, Hirte HW. Intraperitoneal chemotherapy in the first-line treatment of women with stage III epithelial ovarian cancer: a systematic review with metaanalyses. Cancer. Feb 15 2007;109(4):692-702. [Medline].

  3. [Best Evidence] Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. Jan 5 2006;354(1):34-43. [Medline].

  4. Alberts DS, Liu PY, Hannigan EV, et al. Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med. Dec 26 1996;335(26):1950-5. [Medline].

  5. Cochrane Database of Systematic Reviews [database online]. John Wiley & Sons, Ltd; Jan 2006.

  6. Garcia AA. Salvage therapy for ovarian cancer. Curr Oncol Rep. Sep 1999;1(1):64-70. [Medline].

  7. Goff BA, Mandel LS, Melancon CH, Muntz HG. Frequency of symptoms of ovarian cancer in women presenting to primary care clinics. JAMA. Jun 9 2004;291(22):2705-12. [Medline].

  8. Markman M, Liu PY, Wilczynski S, et al. Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy: a Southwest Oncology Group and Gynecologic Oncology Group trial. J Clin Oncol. Jul 1 2003;21(13):2460-5. [Medline].

  9. Mazzeo F, Berliere M, Kerger J, et al. Neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy in patients with primarily unresectable, advanced-stage ovarian cancer. Gynecol Oncol. Jul 2003;90(1):163-9. [Medline].

  10. McGuire WP, Hoskins WJ, Brady MF, et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med. Jan 4 1996;334(1):1-6. [Medline].

  11. NCI Clinical Announcement on Intraperitoneal Chemotherapy in Ovarian Cancer. January 5, 2006: National Cancer Institute; [Full Text].

  12. Ozols RF, Bundy BN, Greer BE, et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. Sep 1 2003;21(17):3194-200. [Medline].

  13. Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet. Jun 21 2003;361(9375):2099-106. [Medline].

  14. Pfisterer J, Plante M, Vergote I, du Bois A, Hirte H, Lacave AJ. Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG. J Clin Oncol. Oct 10 2006;24(29):4699-707. [Medline].

  15. Rebbeck TR, Lynch HT, Neuhausen SL, Narod SA, Van't Veer L, Garber JE. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med. May 23 2002;346(21):1616-22. [Medline].

  16. Rose PG, Nerenstone S, Brady MF, Clarke-Pearson D, Olt G, Rubin SC. Secondary surgical cytoreduction for advanced ovarian carcinoma. N Engl J Med. Dec 9 2004;351(24):2489-97. [Medline].

  17. Sifri R, Gangadharappa S, Acheson LS. Identifying and testing for hereditary susceptibility to common cancers. CA Cancer J Clin. Nov-Dec 2004;54(6):309-26. [Medline].

  18. U.S. Preventive Services Task Force. Screening for ovarian cancer: recommendation statement. U.S. Preventive Services Task Force. Am Fam Physician. Feb 15 2005;71(4):759-62. [Medline].

  19. van der Burg ME, van Lent M, Buyse M, et al. The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer. Gynecological Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer. N Engl J Med. Mar 9 1995;332(10):629-34. [Medline].

  20. Vasey PA, Jayson GC, Gordon A, et al. Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst. Nov 17 2004;96(22):1682-91. [Medline].

  21. White R, Le Van D, McDuff D. Helping the patient in denial: the role of the family in intervention. Md Med J. Jun 1995;44(6):462-6. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Agustin A Garcia, MD, Associate Professor of Medicine, University of Southern California Keck School of Medicine
Agustin A Garcia, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine and American Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Karen Loeb Lifford, MD, Director of General Gynecology, Associate Program Director, Department of Obstetrics and Gynecology, Instructor, Brigham and Women's Hospital, Harvard Medical School
Karen Loeb Lifford, MD is a member of the following medical societies: Association of Professors of Gynecology and Obstetrics, Massachusetts Medical Society, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Antonio V Sison, MD, Program Director, Department of Obstetrics and Gynecology, Robert Wood Johnson University Hospital
Antonio V Sison, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists and Association of Professors of Gynecology and Obstetrics
Disclosure: Nothing to disclose.

CME Editor

Frederick B Gaupp, MD, Consulting Staff, Department of Family Practice, Assumption Community Hospital
Frederick B Gaupp, MD is a member of the following medical societies: American Academy of Family Physicians
Disclosure: Nothing to disclose.

Chief Editor

Michel E Rivlin, MD, Associate Professor, Coordinator, Quality Assurance/Quality Improvement, Department of Obstetrics and Gynecology, University of Mississippi School of Medicine
Michel E Rivlin, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Medical Association, Mississippi State Medical Association, and Royal College of Surgeons of Edinburgh
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.