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Cervical Cancer Medication

  • Author: Cecelia H Boardman, MD; Chief Editor: Warner K Huh, MD  more...
 
Updated: May 31, 2016
 

Medication Summary

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.

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Chemotherapy Agents, Alkylating

Class Summary

Alkylating chemotherapy agents inhibit cell growth and proliferation. They inhibit DNA synthesis through the formation of DNA cross-links.

Cisplatin (Platinol)

 

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 (Ifex)

 

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.

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Antineoplastics, Antimetabolite

Class Summary

Antimetabolite antineoplastic agents inhibit cell growth and proliferation. They interfere with DNA synthesis by blocking the methylation of deoxyuridylic acid.

Fluorouracil (Adrucil)

 

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.

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Antineoplastics, Antimicrotubular

Class Summary

Antimicrotubular antineoplastic agents prevent cell growth and proliferation. They work by enhancing tubulin dimers, stabilizing existing microtubules, and inhibiting their disassembly.

Paclitaxel (Taxol)

 

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.

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Antineoplastics, Topoisomerase Inhibitors

Class Summary

Topoisomerase-inhibiting antineoplastic agents prevent cell growth and proliferation. They work by binding to topoisomerase and causing single-strand DNA breaks.

Topotecan (Hycamtin)

 

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.

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Antineoplastics, VEGF Inhibitor

Class Summary

Vascular endothelial growth factor (VEGF) is crucial to angiogenesis. VEGF inhibitors directly bind to the VEGF protein to disrupt angiogenesis.

Bevacizumab (Avastin)

 

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.

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Vaccines, Inactivated, Viral

Class Summary

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.[10] 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.

Human papillomavirus vaccine, quadrivalent (Gardasil)

 

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.

Human papillomavirus vaccine, bivalent (Cervarix)

 

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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Contributor Information and Disclosures
Author

Cecelia H Boardman, MD Virginia Gynecologic Oncology

Cecelia H Boardman, MD is a member of the following medical societies: Society of Gynecologic Oncology, American College of Obstetricians and Gynecologists, American College of Surgeons, Minnesota Medical Association

Disclosure: Received salary from Merck for speaking and teaching; Received salary from Glaxo for speaking and teaching; Partner received salary from Depuy for speaking and teaching.

Coauthor(s)

Kirk J Matthews, Jr, MD Resident Physician, Department of Obstetrics and Gynecology, Virginia Commonwealth University Medical Center

Disclosure: Nothing to disclose.

Specialty Editor Board

Jori S Carter, MD, MS Assistant Professor, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Virginia Commonwealth University School of Medicine

Jori S Carter, MD, MS is a member of the following medical societies: Alpha Omega Alpha, American College of Obstetricians and Gynecologists, Society of Gynecologic Oncology, Association of Women Surgeons, International Society for Magnetic Resonance in Medicine, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Chief Editor

Warner K Huh, MD Professor, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Senior Scientist, Comprehensive Cancer Center, University of Alabama School of Medicine

Warner K Huh, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American College of Surgeons, Massachusetts Medical Society, Society of Gynecologic Oncology, American Society of Clinical Oncology

Disclosure: I have received consulting fees for: Merck; THEVAX.

Acknowledgements

A David Barnes, MD, PhD, MPH, FACOG Consulting Staff, Department of Obstetrics and Gynecology, Mammoth Hospital (Mammoth Lakes, California), Pioneer Valley Hospital (Salt Lake City, Utah), Warren General Hospital (Warren, Pennsylvania), and Mountain West Hospital (Tooele, Utah)

A David Barnes, MD, PhD, MPH, FACOG is a member of the following medical societies: American College of Forensic Examiners, American College of Obstetricians and Gynecologists, American Medical Association, Association of Military Surgeons of the US, and Utah Medical Association

Disclosure: Nothing to disclose.

Anthony El-Khoueiry, MD Assistant Professor of Medicine, Clinical Instructor, Division of Medical Oncology, Keck School of Medicine, University of Southern California

Disclosure: Nothing to disclose.

Agustin A Garcia, MD Associate Professor of Medicine, Keck School of Medicine, University of Southern California

Disclosure: Nothing to disclose.

Omid Hamid, MD Associate Director of Melanoma Center, Medical Director of Neuro-oncology Clinic, USC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California

Disclosure: Nothing to disclose.

John J Kavanagh Jr MD, Chief, Professor, Department of Internal Medicine, Section of Gynecological and Medical Therapeutics, MD Anderson Cancer Center, University of Texas Medical School at Houston

John J Kavanagh Jr is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association for the History of Medicine, American College of Physicians, American Federation for Medical Research, American Medical Association, Society of Gynecologist Oncologists, Southern Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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Cervical carcinoma with adnexa.
Squamous cell cervical carcinoma.
Cervical intraepithelial neoplasia grade I.
Cervical intraepithelial neoplasia grade III.
CT scan of cervical cell carcinoma demonstrates markedly enlarged lymph node at left pelvic sidewall. This is consistent with pelvic lymph node metastasis, which is indicative of stage IIIB disease. Cystic consistency is not unusual for metastatic cervical carcinoma. Primary tumor is well depicted as hypoattenuating circumscribed mass. Cyst is present in anteriorly located left ovary.
Table 1. Human Papillomavirus Types Associated With Cervical Cancer
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.
Table 2. Cervical Cancer Staging: Primary Tumor (T)
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)
M1 IVB Distant metastasis
Table 3. UICC/AJCC Staging for Cervical Cancer
Stage Tumor Node Metastasis
0 Tis N0 M0
IA1 T1a1 N0 M0
IA2 T1a2 N0 M0
IB1 T1b1 N0 M0
IIA T2a N0 M0
IIB T2b N0 M0
IIIA T3a N0 M0
IIIB T1 N1 M0
- T2 N1 M0
- T3a N1 M0
- T3b Any N M0
IVA T4 Any N M0
IVB Any T Any N M1
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