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      News & Perspective Drugs & Diseases CME & Education Academy Video Decision Point
      Drugs & Diseases > Oncology

      Ovarian Cancer Medication

      Updated: Nov 17, 2022
      • Author: Andrew E Green, MD; Chief Editor: Yukio Sonoda, MD  more...
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      Medication

      Medication Summary

      Chemotherapy for ovarian cancer is used in neoadjuvant, adjuvant, and maintenance therapy. Agents used include bevacizumab, platinum-based regimens, and poly (ADP-ribose) polymerase (PARP) inhibitors.

      Standard postoperative chemotherapy is combination therapy with platinum and paclitaxel. Carboplatin plus paclitaxel is the preferred initial regimen. Randomized studies have proved that cisplatin plus paclitaxel produces equivalent survival rates, but the combination of carboplatin and paclitaxel is preferred because of its more tolerable toxicity profile. If patients are treated with cisplatin, paclitaxel should be administered as a 24-hour infusion to decrease the risk of neurotoxicity. Another alternative is to combine carboplatin with docetaxel.

      The combination of paclitaxel and carboplatin is customarily given every 3 weeks (day 1 of a 21-day cycle). Because the addition of other drugs to this regimen has proved disappointing, Katsumata et al studied the use of a dose-dense regimen, in which paclitaxel is given on days 1, 8, and 15 and carboplatin is given on day 1. [67] Compared with the conventional regimen, the dose-dense regimen resulted in longer median progression-free survival (28.0 mo versus 17.2 mo) and higher overall survival at 3 years (72.1% versus 65.1%). Early discontinuation was more common with the dose-dense regimen, and these patients were more likely to experience toxicity, especially neutropenia and anemia.

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      Chemotherapy agents

      Class Summary

      Cisplatin, carboplatin, and paclitaxel are chemotherapy agents approved for the initial treatment of ovarian cancer. Intrastrand cross-linking of DNA and inhibition of DNA precursors are among proposed mechanisms of action for cisplatin. The mechanism of action for paclitaxel is tubulin polymerization and microtubule stabilization. A study by Hetland et al found that class III beta-tubulin expression in prechemotherapy effusions is associated with poor response and shorter survival; thus, it may be a successful therapeutic target in ovarian cancer. [143]

      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)

      Indicated in established combination therapy in patients with metastatic ovarian tumors who have already received appropriate surgical and/or radiotherapeutic procedures. It also is indicated as secondary therapy in patients with metastatic ovarian tumors refractory to standard chemotherapy who have not previously received cisplatin therapy. For cisplatin, intrastrand cross-linking of DNA and inhibition of DNA precursors are among the proposed mechanisms of action.

      Carboplatin

      For carboplatin, intrastrand cross-linking of DNA and inhibition of DNA precursors are among the proposed mechanisms of action.

      Paclitaxel (Taxol)

      Indicated as subsequent therapy for the treatment of advanced carcinoma of the ovary. As first-line therapy, paclitaxel is indicated in combination with cisplatin. The mechanism of action of paclitaxel is tubulin polymerization and microtubule stabilization.

      Liposomal doxorubicin (Doxil)

      Liposomal doxorubicin interferes with synthesis of nucleic acid by intercalating with DNA nucleotide pairs and topoisomerase II inhibition. Indicated for the treatment of patients with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy.

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      Antineoplastic Agents

      Class Summary

      Antineoplastic agents inhibit cell growth and proliferation. Several antineoplastic 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).

      Etoposide

      Etoposide is a glycosidic derivative of podophyllotoxin that exerts its cytotoxic effect through stabilization of the normally transient covalent intermediates formed between DNA substrate and topoisomerase II, leading to single- and double-strand DNA breaks.

      Topotecan (Hycamtin)

      Topotecan binds to the topoisomerase I‑DNA complex and prevents religation of single-strand breaks.  Indicated as monotherapy for the treatment of patients with metastatic ovarian cancer after disease progression on or after initial or subsequent chemotherapy.

      Gemcitabine (Gemzar)

      Gemcitabine is a cytidine analog that is metabolized intracellularly to an active nucleotide. It inhibits ribonucleotide reductase and competes with deoxycytidine triphosphate for incorporation into DNA. It is indicated for advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy and is used in combination with carboplatin. It is cell-cycle specific for the S phase.

      Docetaxel (Taxotere)

      Docetaxel is a semisynthetic taxane, a class of drugs that inhibits cancer cell growth by promoting assembly and blocking the disassembly of microtubules, thereby preventing cancer cell division, leading to cell death.

      Vinorelbine (Navelbine)

      Vinorelbine is a semisynthetic vinca alkaloid that inhibits tubulin polymerization during G2 phase of cell division, thereby inhibiting mitosis.

      Ifosfamide

      Ifosfamide inhibits DNA and protein synthesis and, thus, cell proliferation, by causing DNA cross-linking and denaturation of double helix.

      Fluorouracil (Adrucil)

      Fluorouracil (5-FU) is a cycle-specific agent that has activity as single agent and, for many years, has been combined with biochemical modulator leucovorin. 5-FU inhibits tumor cell growth through at least 3 different mechanisms that ultimately disrupt DNA synthesis or cellular viability.

      Melphalan (Alkeran)

      Melphalan inhibits mitosis by cross-linking DNA strands. Tablets are indicated for the palliation of nonresectable epithelial ovarian carcinoma.

      Altretamine (Hexalen)

      The mechanism of action of altretamine is unclear; reactive intermediates covalently bind to microsomal proteins and DNA, possibly causing DNA damage. Altretamine inhibits DNA and RNA synthesis by inhibiting the incorporation of radioactive thymidine and uridine into DNA and RNA. Indicated as palliative treatment of patients with persistent or recurrent ovarian cancer.

      Bevacizumab (Avastin)

      Bevacizumab is a recombinant humanized monoclonal antibody to vascular endothelial growth factor (VEGF) receptors. Blocking the angiogenic VEGF receptor, in turn inhibits tumor angiogenesis, starving tumor of blood and nutrients. It is indicated in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan for platinum-resistant recurrent epithelial ovarian cancer in patients who received no more than 2 prior chemotherapy regimens. It is also indicated for women with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer either in combination with carboplatin and paclitaxel or in combination with carboplatin and gemcitabine chemotherapy, followed by bevacizumab alone.

      Mirvetuximab soravtansine (Elahere)

      Indicated for women with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received 1-3 prior systemic treatment regimens. Mirvetuximab soravtansine is an antibody-drug conjugate consisting of an anti-FRα antibody linked to maytansinoid DM4 (a tubulin-targeting agent).  

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      PARP Inhibitors

      Class Summary

      Inhibition of poly (ADP-ribose) polymerase (PARP) enzymes result in disruption of cellular homeostasis and cell death.

      Olaparib (Lynparza)

      Olaparib is an inhibitor of PARP enzymes, including PARP1, PARP2, and PARP3. PARP enzymes are involved in normal cellular homeostasis (eg, DNA transcription, cell cycle regulation, DNA repair). Available as either tablets or capsules. The tablets and capsules are not interchangeable on a mg-to-mg basis due to differences in the dosing and bioavailability of each formulation, and therefore, should not be substituted with one another. The capsules and tablets are indicated as monotherapy for deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer in patients who have been treated with 3 or more prior lines of chemotherapy. Additionally, the tablets are approved for maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy. Discontinue bevacizumab before initiating maintenance therapy.

      Rucaparib (Rubraca)

      By inhibiting PARP, rucaparib may cause increased formation of PARP-DNA complexes, resulting in DNA damage, apoptosis, and cell death. Increased cytotoxicity due to rucaparib was observed in tumor cell lines deficient in BRCA1/2 and other DNA repair genes. Indicated for monotherapy of women with deleterious BRCA mutation (germline and/or somatic) associated with advanced ovarian cancer who have been treated with ≥2 prior lines of chemotherapy. Also, indicated for the maintenance treatment of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. 

      Niraparib (Zejula)

      Niraparib is a highly selective for PARP-1 and PARP-2. PARP-1 and PARP-2 are involved in detecting DNA damage and promote repair. Inhibiting PARP enzymatic activity results in DNA damage, apoptosis and cell death. PARP inhibitor that is active both in patients with and those without BRCA mutations. Indicated for the maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. Discontinue bevacizumab before initiating maintenance therapy.

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      Cytoprotective Agents

      Class Summary

      Mesna is indicated in the prevention of hemorrhagic cystitis in patients being treated with ifosfamide and cyclophosphamide.

      Mesna (Mesnex)

      Mesna detoxifies metabolites of ifosfamide and cyclophosphamide. Usage is somewhat controversial, but it is commonly accepted that the total dose should be at least 60% of the total dose of the alkylating agent.

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      Antiemetics

      Class Summary

      Antiemetics are used for the prevention and treatment of nausea and vomiting associated with chemotherapy.

      Ondansetron (Zofran)

      Ondansetron is a selective 5-HT3 receptor antagonist that blocks serotonin both peripherally and centrally. It prevents nausea and vomiting associated with emetogenic cancer chemotherapy (eg, high-dose cisplatin) and complete body radiotherapy.

      Granisetron (Kytril)

      Granisetron is also a 5-HT3-receptor antagonist. It is indicated for the prevention of nausea and vomiting associated with initial and repeat courses of emetogenic chemotherapy, including high-dose cisplatin.

      Palonosetron (Aloxi)

      Palonosetron is a selective 5-HT3 receptor antagonist with long half-life (40 h). It is indicated for the prevention and treatment of chemotherapy-induced nausea and vomiting. Palonosetron blocks 5-HT-3 receptors peripherally and centrally in the chemoreceptor trigger zone.

      Dexamethasone (Decadron)

      Dexamethasone is used as an antiemetic in low doses during chemotherapy. It is usually employed in multiagent antiemetic regimens with 5HT-3 receptor antagonists.

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