Cervical Cancer Medication
- Author: Cecelia H Boardman, MD; Chief Editor: Warner K Huh, MD more...
Chemotherapy should be administered in conjunction with radiation therapy to most patients with stage IB (high-risk) to stage IVA cervical cancer. Cisplatin is the agent used most commonly, although 5-fluorouracil also is used frequently. For patients with metastatic disease, cisplatin remains the most active agent. Topotecan, ifosfamide, and paclitaxel also have significant activity in this setting. The combination of topotecan and cisplatin improves overall survival. However, acute toxicities are also increased.
Chemotherapy Agents, Alkylating
Alkylating chemotherapy agents inhibit cell growth and proliferation. They inhibit DNA synthesis through the formation of DNA cross-links.
Intrastrand cross-linking of DNA and inhibition of DNA precursors are among the proposed mechanisms of action for cisplatin. This agent is used in combination with radiation therapy.
Ifosfamide forms DNA interstrand and intrastrand bonds that interfere with protein synthesis. Although the US Food and Drug Administration (FDA) has approved this agent only for the treatment of testicular cancer, it has several off-label indications, including treatment of cervical cancer.
Antimetabolite antineoplastic agents inhibit cell growth and proliferation. They interfere with DNA synthesis by blocking the methylation of deoxyuridylic acid.
Fluorouracil is a pyrimidine antimetabolite. Several mechanisms of action have been proposed, including inhibition of thymidylate synthase and inhibition of RNA synthesis. This agent is also a potent radiosensitizer.
Antimicrotubular antineoplastic agents prevent cell growth and proliferation. They work by enhancing tubulin dimers, stabilizing existing microtubules, and inhibiting their disassembly.
The mechanisms of action of paclitaxel are tubulin polymerization and microtubule stabilization. This agent also participates in the breakage of chromosomes and modulation of immune response.
Antineoplastics, Topoisomerase Inhibitors
Topoisomerase-inhibiting antineoplastic agents prevent cell growth and proliferation. They work by binding to topoisomerase and causing single-strand DNA breaks.
Topotecan inhibits topoisomerase I, inhibiting DNA replication. It acts in the S phase of the cell cycle. Patients who have received prior chemotherapy should be given a lower dose initially.
Antineoplastics, VEGF Inhibitor
Vascular endothelial growth factor (VEGF) is crucial to angiogenesis. VEGF inhibitors directly bind to the VEGF protein to disrupt angiogenesis.
Bevacizumab is a recombinant humanized monoclonal antibody to VEGF. It blocks the angiogenic molecule VEGF, thereby inhibiting tumor angiogenesis and starving the tumor of blood and nutrients. It is indicated as part of a combination chemotherapy regimen for persistent, recurrent, or metastatic carcinoma of the cervix.
Vaccines, Inactivated, Viral
Two human papillomavirus (HPV) vaccines are now available for prevention of HPV-associated dysplasias and neoplasias, including cervical cancer, genital warts (condylomata acuminata), and precancerous genital lesions. The immunization series should be completed in girls and young women aged 9-26 years. The duration of protection is not yet known, but follow-up to date has found sustained immunogenicity and efficacy more than 8 years after vaccination.
The quadrivalent recombinant HPV vaccine is indicated to prevent disorders secondary to infection from HPV types 6, 11, 16, and 18, including cervical cancer, genital warts (condylomata acuminata), and the following precancerous genital lesions:
- Cervical adenocarcinoma in situ
- Cervical intraepithelial neoplasia (CIN) grades 1, 2, and 3
- Vulvar intraepithelial neoplasia grades 2 and 3
- Vaginal intraepithelial neoplasia grades 2 and 3
The efficacy of the vaccine is mediated by humoral immune responses following the immunization series.
The bivalent recombinant HPV vaccine is prepared from the L1 protein of HPV types 16 and 18. It is indicated for girls and women (ages 9-25 years) to prevent the following diseases caused by oncogenic HPV types 16 and 18:
- Cervical cancer
- CIN grade 2 or higher
- Cervical adenocarcinoma in situ
- CIN grade 1
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|HPV Alpha Group||Types||Evidence for Cervical Cancer Causation|
|1||16||Most carcinogenic HPV type, known to cause cancer at several sites|
|18,31,33,35,39,45,51,52,56,58, 59||Sufficient evidence|
|2A||68||Limited evidence in humans and strong mechanistic evidence|
|2B||26,53,66,67,70,73,82||Limited evidence in humans|
|30,34,69,85,97||Classified by phylogenetic analogy to HPV types with sufficient or limited evidence in humans|
|3||6,11||Inadequate epidemiological evidence and absence of carcinogenic potential in mechanistic studies|
|HPV = human papillomavirus.|
|TNM Stage||FIGO Stage|
|TX||-||Primary tumor cannot be assessed|
|T0||-||No evidence of primary tumor|
|Tis||0||Carcinoma in situ|
|T1||I||Cervical carcinoma confined to uterus (extension to corpus should be disregarded)|
|T1a||IA||Invasive carcinoma diagnosed only by microscopy. All macroscopically visible lesions—even with superficial invasion—are T1b/1B. Stromal invasion with a maximal depth of 5.0 mm measured from the base of the epithelium and a horizontal spread of 7.0 mm or less. Vascular space involvement, venous or lymphatic, does not affect classification.|
|T1a1||IA1||Measured stromal invasion 3 mm or less in depth and 7 mm or less in lateral spread|
|T1a2||IA2||Measured stromal invasion more than 3 mm but not more than 5 mm with a horizontal spread 7 mm or less|
|T1b||IB||Clinically visible lesion confined to the cervix or microscopic lesion greater than IA2|
|T1b1||IB1||Clinically visible lesion 4 cm or less in greatest dimension|
|IB2||Clinically visible lesion more than 4 cm|
|T2||II||Cervical carcinoma extends beyond the cervix but not to the pelvic sidewall or to the lower third of vagina|
|T2a||IIA||Tumor without parametrial invasion|
|T2b||IIB||Tumor with parametrial invasion|
|T3||III||Tumor extends to the pelvic wall and/or involves the lower third of the vagina and/or causes hydronephrosis or nonfunctioning kidney|
|T3a||IIIA||Tumor involves lower third of vagina; no extension to pelvic sidewall|
|T3b||IIIB||Tumor extends to pelvic sidewall and/or causes hydronephrosis or nonfunctioning kidney|
|-||IV||Cervical carcinoma has extended beyond the true pelvis or has involved (biopsy proven) the bladder mucosa or rectal mucosa. Bullous edema does not qualify as a criteria for stage IV disease.|
|T4||IVA||Spread to mucosa of adjacent organs (bladder, rectum, or both)|
|IVB||Any T||Any N||M1|