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.
Cisplatin
Indicated in established combination therapy or single-line therapy in patients with metastatic, recurrent, or high-risk endometrial carcinoma. The proposed mechanisms of action are by intrastrand cross-linking of DNA and inhibition of DNA precursors.
Carboplatin
The proposed mechanisms of action are intrastrand cross-linking of DNA and inhibition of DNA precursors.
Paclitaxel (Taxol)
Indicated as subsequent therapy for the treatment of advanced endometrial carcinoma. As first-line therapy, paclitaxel is indicated in combination with carboplatin. The mechanism of action of paclitaxel is tubulin polymerization and microtubule stabilization.
Paclitaxel protein bound (Abraxane)
Paclitaxel protein bound is a microtubular inhibitor (albumin-conjugated formulation) and a natural taxane that prevents depolymerization of cellular microtubules, which results in DNA, RNA, and protein synthesis inhibition. It is used as a substitute for patients with a hypersensitivity to paclitaxel.
Doxorubicin
Doxorubicin is a cytotoxic anthracycline that inhibits topoisomerase II and produces free radicals, which may cause destruction of DNA. It blocks DNA and RNA synthesis by inserting between adjacent base pairs and binding to the sugar-phosphate backbone of DNA, which causes DNA polymerase inhibition. It binds to nucleic acids, presumably by specific intercalation of the anthracycline nucleus with the DNA double helix.
This agent is also a powerful iron chelator. The iron-doxorubicin complex induces production of free radicals that can destroy DNA and cancer cells. Maximum toxicity occurs during the S phase of the cell cycle.
Doxorubicin liposomal (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 endometrial cancer whose disease has progressed or recurred after platinum-based chemotherapy.
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.
Ifosfamide
Ifosfamide inhibits DNA and protein synthesis and, thus, cell proliferation, by causing DNA cross-linking and denaturation of double helix.
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 endometrial cancer after disease progression on or after initial or subsequent chemotherapy.
Monoclonal Antibodies
Class Summary
Monoclonal antibodies have been engineered to react against specific antigens on cancer cells, which can help to enhance the patient’s immune response and prevent cancer cell growth.
Trastuzumab (Herceptin, Ogivri, Herzuma, Ontruzant, Trazimera, trastuzumab-dkst, trastuzumab-pkrb, trastuzumab-dttb, trastuzumab-qyyp)
Trastuzumab is a monoclonal antibody that binds to extracellular HER2. It mediates antibody-dependent cellular cytotoxicity against cells that overproduce HER2. Used in combination with carboplatin and paclitaxel for patients with HER-2 positive uterine serous carcinoma.
The combination of trastuzumab and an anthracycline is associated with significant cardiac toxicity.
Bevacizumab (Avastin)
Bevacizumab is a murine-derived monoclonal antibody that inhibits angiogenesis by targeting and inhibiting vascular endothelial growth factor (VEGF). It inhibits new blood vessel formation, denying blood, oxygen, and other nutrients needed for tumor growth. It may be considered in patients who have progressed on prior cytotoxic chemotherapy for recurrent, metastatic, or high-risk endometrial cancer.
PD-1/PD-L1 Inhibitors
Class Summary
Monoclonal antibodies that bind the programmed cell death-1 protein (PD-1) ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T cell proliferation and cytokine production.
Pembrolizumab (Keytruda)
It is indicated in combination with lenvatinib for the treatment of advanced endometrial cancer who have disease progression following prior systemic therapy. The indication applies to patients who are not candidates for curative surgery or radiation and who have disease that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). It is also indicated for unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mut/Mb] solid tumors in patients that have progressed following prior treatment and who have no alternative treatment options.
Dostarlimab (Jemperli)
Dostarlimab is a monoclonal antibody that blocks interaction with PD-L1 and PD-L2, releasing PD-1 pathway–mediated inhibition of the immune response, including antitumor immune response. It is indicated in combination with carboplatin and paclitaxel followed by single-agent dostarlimab for patients with primary advanced or recurrent endometrial cancer that is mismatch repair–deficient (dMMR) or microsatellite instability–high (MSI-H).
Antineoplastics, VEGF Inhibitor
Class Summary
Inhibits the kinase activities of various subtypes of vascular endothelial growth factor (VEGF) receptors.
Lenvatinib (Lenvima)
Lenvatinib is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). It also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; the platelet-derived growth factor receptor alpha (PDGFR-α); KIT; and RET. It is indicated in combination with pembrolizumab for the treatment of advanced endometrial cancer who have disease progression following prior systemic therapy.
Antineoplastics, Estrogen Receptor Antagonist
Class Summary
Selective estrogen receptor modulators (SERMs) stimulate or inhibit the estrogen receptors of various target tissues. Hormonal therapy is typically used for lower-grade endometrioid histologies, preferably in patients with small tumor volume or an indolent growth pace.
Tamoxifen (Soltamox)
Tamoxifen is a nonsteroid with potent antiestrogenic effects in the breast; however, it may be an estrogen agonist in the uterus.
Aromatase Inhibitors
Class Summary
Aromatase inhibitors play a role in adjuvant therapy in endometrial cancer. These agents work by inhibiting aromatase, the enzyme responsible for converting other steroid hormones into estrogen. Hormonal therapy is typically used for lower-grade endometrioid histologies, preferably in patients with small tumor volume or an indolent growth pace.
Letrozole (Femara)
Letrozole is a nonsteroidal competitive inhibitor of the aromatase enzyme system. It inhibits the conversion of androgens to estrogens.
Progestins
Class Summary
All progestational agents act by decidualization and atrophy of the endometrium. Use of this category of drugs relies on high-dose hormones to suppress the hypothalamus through negative feedback. This results in a hypoestrogenic state. Hormonal therapy is typically used for lower-grade endometrioid histologies, preferably in patients with small tumor volume or an indolent growth pace.
Medroxyprogesterone (Depo-SubQ Provera 104, DepoProvera, MPA)
Medroxyprogesterone inhibits secretion of gonadotropins, thereby inhibiting ovulation and decreasing the thickness of the endometrium.
Levonorgestrel intrauterine (Kyleena, Liletta, Mirena)
The levonorgestrel-releasing intrauterine device inhibits secretion of gonadotropins, thereby inhibiting ovulation and decreasing the thickness of the endometrium.
Cytoprotective Agents
Class Summary
Mesna is indicated in the prevention of hemorrhagic cystitis in patients being treated with ifosfamide.
Mesna (Mesnex)
Mesna detoxifies metabolites of ifosfamide and cyclophosphamide. The usual total dose should be at least 60% of the total dose of the alkylating agent.
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Diagnostic hysteroscopy for endometrial cancer. Video courtesy of Tarek Bardawil, MD.
Tables
Primary tumor (T) |
||
TNM |
FIGO stages |
Surgical-pathologic findings |
TX |
Primary tumor cannot be assessed |
|
T0 |
No evidence of primary tumor |
|
T1 |
I |
Tumor confined to uterus |
T1a |
IA |
Tumor ≤5 cm |
T1b |
IB |
Tumor >5 cm |
T2a |
IIA |
Tumor extends to the pelvis, adnexal involvement |
T2b |
IIB |
Tumor extends to extra-uterine pelvic tissue |
T3a |
IIIA |
Tumor invades abdominal tissues, one site |
T3b |
IIIB |
Tumor invades more than one site |
T4 |
IVA |
Tumor invades bladder and/or rectum |
Regional lymph nodes (N) |
||
TNM |
FIGO stages |
Surgical-pathologic findings |
NX |
Regional lymph nodes cannot be assessed |
|
N0 |
No regional lymph node metastasis |
|
N1 |
IIIC |
Metastasis to pelvic and/or para-aortic lymph nodes |
Distant metastasis (M) |
||
TNM |
FIGO stages |
Surgical-pathologic findings |
M0 |
No distant metastasis |
|
M1 |
IVB |
Distant metastasis |
