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)
- Conization
- Hysterectomy for postreproductive patients
- Internal radiation therapy for medically inoperable patients
Stage IA cervical cancer
- Conization
- Total hysterectomy
- Modified radical hysterectomy with lymphadenectomy
- Radical trachelectomy
- Intracavitary radiation therapy
- Radiation therapy with concomitant chemotherapy
Stages IB, IIA cervical cancer
- Radiation therapy with concomitant chemotherapy
- Radical hysterectomy and bilateral pelvic lymphadenectomy with or without total pelvic radiation therapy plus chemotherapy
- Radical trachelectomy
- Neoadjuvant chemotherapy
- Radiation therapy alone
- Intensity Modulated Radiation Therapy (IMRT)
Stages IIB, III, and IVA cervical cancer
- Radiation therapy with concomitant chemotherapy
- Neoadjuvant chemotherapy
- Interstitial brachytherapy
Stage IVB cervical cancer
- Palliative radiation therapy
- Palliative chemotherapy
Recurrent cervical cancer
- Radiation therapy and chemotherapy
- Palliative chemotherapy
- Pelvic exenteration
Radiation therapy
In Situ Cervical Cancer
- 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 concomitantchemotherapy
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.
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.
- Radical hysterectomy and bilateral pelvic lymphadenectomy with or without total pelvic radiation therapy pluschemotherapy
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
- Radiation therapy with concomitant chemotherapy
- 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).
- Interstitial [[ brachytherapy]]
- 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
- Radiation therapy andchemotherapy
- 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
- Radiation therapy with concomitant chemotherapy
- Concurrent, cisplatin-based chemotherapy with radiation therapy is the standard of care for women who require radiation therapy for treatment of cervical cancer
- Neoadjuvant chemotherapy
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
- Radiation therapy with concomitant chemotherapy
- 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
- Palliative chemotherapy
Drugs used in stage IVB cervical cancer treatment are shown in table below[2]
| 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
- Palliative chemotherapy
Drugs used in Recurrent Cervical Cancer treatment are shown in table below[3]
| 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) |