Cervical cancer medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Monalisa Dmello, M.B,B.S., M.D. [2]

Overview

The optimal therapy for cervical cancer depends on the stage at diagnosis.

Medical Therapy

Patterns-of-care studies clearly demonstrate the negative prognostic effect of increasing tumor volume and spread pattern.Treatment, therefore, may vary within each stage as the individual stages are currently defined by Féderation Internationale de Gynécologie et d’Obstétrique (FIGO).[1]

  • Standard Treatment Options for cervical cancer

In situ carcinoma of the cervix (this stage is not recognized by FIGO)

Stage IA cervical cancer

Stages IB, IIA cervical cancer

Stages IIB, III, and IVA cervical cancer

Stage IVB cervical cancer

Recurrent cervical cancer

Radiation therapy

In Situ Cervical Cancer[2]

  • Internal radiation therapy for medically inoperable patients

For medically inoperable patients, a single intracavitary insertion with tandem and ovoids for 5,000 mg hours (80 Gy vaginal surface dose) may be used.

Stage IA Cervical Cancer

  • Intracavitary radiation therapy

Intracavitary radiation therapy is a treatment option when palliative treatment is appropriate because of other medical conditions and for women who are not surgical candidates. If the depth of invasion is less than 3 mm and no capillary lymphatic space invasion is noted, and the frequency of lymph-node involvement is sufficiently low, external-beam radiation therapy is not required. One or two insertions with tandem and ovoids for 6,500 mg to 8,000 mg hours (100–125 Gy vaginal surface dose) are recommended.

Stages IB and IIA Cervical Cancer

  • Radiation therapy with concomitant chemotherapy
  • Concurrent, cisplatin-basedchemotherapy with radiation therapy is the standard of care for women who require radiation therapy for treatment of cervical cancer. Radiation therapy protocols for patients with cervical cancer have historically used dosing at two anatomical points, termed point A and point B, to standardize the doses received. Point A is defined as 2 cm from the external os, and 2 cm lateral, relative to the endocervical canal. Point B is also 2 cm from the external os, and 5 cm lateral from the patient midline, relative to the bony pelvis. In general, for smaller tumors, the curative-intent dose for point A is around 70 Gy, whereas for larger tumors, the point A dose may approach 90 Gy.
  • Brachytherapy

Standard radiation therapy for cervical cancer includes brachytherapy after external-beam radiation therapy (EBRT). Although low-dose rate (LDR) brachytherapy, typically with cesium Cs 137, has been the traditional approach, the use of high-dose rate (HDR) therapy, typically with iridium Ir 192, is rapidly increasing. HDR brachytherapy provides the advantage of eliminating radiation exposure to medical personnel, a shorter treatment time, patient convenience, and improved outpatient management.

The radiation therapy included EBRT and one Cs-137 LDR insertion, with a total dose to point A from 70 to 90 Gy (median 76 Gy)

  • Adjuvant radiation therapy post surgery
  • Radiation therapy alone

External-beam pelvic radiation therapy combined with two or more intracavitary brachytherapy applications is appropriate therapy for patients with stage IA2 and IB1 lesions. For patients with stage IB2 and larger lesions, radiosensitizingchemotherapy is indicated. The role of radiosensitizing chemotherapy in patients with stage IA2 and IB1 lesions is untested. However, it may prove beneficial in certain cases.

  • IMRT

IMRT is a radiation therapy technique that allows for conformal dosing of target anatomy while sparing neighboring tissue. Theoretically, this technique should decrease radiation therapy–related toxicity, but this could come at the cost of decreased efficacy if tissue is inappropriately excluded from the treatment field. Several institutions have reported their experience with IMRT for postoperative adjuvant therapy in patients with intermediate-risk and high-risk disease after radical surgery. The Radiation Therapy Oncology Group (RTOG) has closed accrual for a phase II trial (RTOG-0418 [NCT00331760]) that is evaluating the use of IMRT in patients with both cervical and endometrial cancers who require adjuvant radiation therapy.

Stages IIB, III, and IVA Cervical Cancer

  • For patients who complete EBRT and have bulky cervical disease such that standard brachytherapy cannot be placed anatomically, interstitial brachytherapy has been used to deliver adequate tumoricidal doses with an acceptable toxicity profile.

Stage IVB Cervical Cancer

  • Palliative radiation therapy
  • Radiation therapy may be used to palliate central disease or distant metastases

Recurrent Cervical Cancer

  • For recurrence in the pelvis after initial radical surgery, radiation therapy andchemotherapy (fluorouracil with or without mitomycin) may cure 40% to 50% of patients.

Chemotherapy

Stages IB and IIA Cervical Cancer[3]

  • Concurrent, cisplatin-based chemotherapy with radiation therapy is the standard of care for women who require radiation therapy for treatment of cervical cancer

EORTC-55994 (NCT00039338) randomly assigned patients with stages IB2, IIA2, and IIB cervical cancer to standard chemoradiation or neoadjuvant chemotherapy (with a cisplatin backbone for three cycles) followed by evaluation for surgery. With OS as the primary endpoint, this trial may delineate whether there is a role for neoadjuvant chemotherapy for this patient population.

Stages IIB, III, and IVA Cervical Cancer

  • Strong consideration should be given to the use of intracavitary radiation therapy and external-beam radiation therapy (EBRT) to the pelvis combined with cisplatin or cisplatin/fluorouracil (5FU)

Stage IVB Cervical Cancer[4]

Drugs used in stage IVB cervical cancer treatment are shown in table below[5]

Drug Name Response Rate
Cisplatin 15%–25%
Ifosfamide 31%
Paclitaxel 17%
Ifosfamide/cisplatin 31%
Irinotecan 21% in patients previously treated with chemotherapy
Paclitaxel/cisplatin 46%
Cisplatin/gemcitabine 41%
Cisplatin/topotecan 27%

Recurrent Cervical Cancer[6]

Drugs used in Recurrent Cervical Cancer treatment are shown in table below[7]

Drug Name Response Rate
Cisplatin 15%–25%
Ifosfamide 31%
Paclitaxel 17%
Ifosfamide/cisplatin 31%
Irinotecan 21% in patients previously treated with chemotherapy
Paclitaxel/cisplatin 46%
Cisplatin/gemcitabine 41%
Cisplatin/topotecan 27%
Cisplatin/vinorelbine 30%
Bevacizumab 11%; 24% survived progression free for at least 6 months, as seen in GOG-0227C(NCT00025233)

References


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