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Cervical Cancer Treatment (PDQ®)

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Recurrent Cervical Cancer Treatment

Treatment Options for Recurrent Cervical Cancer
        Radiation therapy and chemotherapy
        Palliative chemotherapy
        Pelvic exenteration
Treatment Options Under Clinical Evaluation for Recurrent Cervical Cancer
Current Clinical Trials



Treatment Options for Recurrent Cervical Cancer

Treatment options for recurrent cervical cancer include the following:

  1. Radiation therapy and chemotherapy.
  2. Palliative chemotherapy.
  3. Pelvic exenteration.
Radiation therapy and chemotherapy

For recurrence in the pelvis after initial radical surgery, radiation therapy and chemotherapy (fluorouracil with or without mitomycin) may cure 40% to 50% of patients.[1]

Palliative chemotherapy

Chemotherapy can be used for palliation. Drugs used for palliative chemotherapy are shown in Table 7.

Table 7. Drugs Used to Treat Recurrent Cervical Cancer
Drug name Response rate 
Cisplatin [2]15%–25%
Ifosfamide [3,4]15%–30%
Paclitaxel [5]17%
Irinotecan [6]21% in patients previously treated with chemotherapy
Bevacizumab [7]11%; 24% survived progression free for at least 6 months, as seen in GOG-0227C (NCT00025233)
Ifosfamide/cisplatin [8,9]31%
Paclitaxel/cisplatin [10]46%
Cisplatin/gemcitabine [11]41%
Cisplatin/topotecan [12]27%
Cisplatin/vinorelbine [13]30%

Cisplatin in combination with other drugs

Single-agent cisplatin administered intravenously at 50 mg/m² every 3 weeks has been the regimen most often used to treat recurrent cervical cancer since the drug was initially introduced in the 1970's.[2] More recently, the GOG has reported on sequential randomized trials dealing with combination chemotherapy for stage IVB, recurrent, or persistent cervical cancer.[9,12,14-17]

Evidence (cisplatin in combination with other drugs):

  1. GOG-110, GOG-0179, GOG-0169 (NCT00803062)
    • GOG 110: The ifosfamide + cisplatin combination was superior to cisplatin alone in the secondary endpoint of response rates, but at the cost of increased toxicity.

    • GOG 0179: The cisplatin + topotecan (CT) doublet combination had a significant advantage in overall survival (OS) compared with cisplatin alone, leading to approval of this indication for topotecan by the U.S. Food and Drug Administration. However, cisplatin alone underperformed in this trial because as many as 40% of the patients had already received cisplatin up front as a radiosensitizer.[12]

    • GOG 0169: The paclitaxel + cisplatin (PC) combination, similarly, was superior in response rates and progression-free survival (PFS), and its toxicity was similar to that of the single agent except in patients with GOG performance status 2 (scale: 0, asymptomatic–4, totally bedridden). Therefore, paclitaxel plus cisplatin (PC) was chosen as the reference arm in GOG-0204 (NCT00064077).

  2. GOG-0204 enrolled 513 patients and compared four cisplatin-based doublet regimens. The trial was closed early because no one experimental arm was likely to significantly lower the hazard ratio of death relative to PC:[17]
    • 1.15 (95% confidence interval [CI], 0.79–1.67) for vinorelbine + cisplatin (VC).

    • 1.32 (95% CI, 0.91–1.92) for gemcitabine plus cisplatin.

    • 1.27 (95% CI, 0.90–1.78) for CT. Trend in RR, PFS, and OS favored CT.

    • The patients in the various arms of the study differed in the extent of neutropenia, infection, and alopecia that they experienced,[17] but none of the patients in the study arms differed in health-related quality of life during treatment.[18] However, there were more neurologic side effects for PC.

  3. GOG-0240 (NCT00803062) was designed to answer the following two questions:[19]
    • Can a nonplatinum combination show improvement over the standard of cisplatin-paclitaxel in this population previously treated with cisplatin during radiation therapy?

    • Can the addition of bevacizumab improve upon combination chemotherapy in patients with stage IVB, persistent or recurrent cervical cancer?

    Patients were randomly assigned to the following four treatment arms:

    • Cisplatin (50 mg/m2) + paclitaxel (135 mg/m2 or 175 mg/m2) on day 1 (PC).

    • PC + bevacizumab (15mg/kg) on day 1.

    • Topotecan (0.75 mg/m2) d1–d3 + paclitaxel (175 mg/m2) on day 1 (PT).

    • PT + bevacizumab (15mg/kg) on day 1.

    Additional study methods and results included the following:

    • The primary endpoint was OS, and 452 patients were evaluable.

    • The combination PT was not superior to PC and had a hazard ratio (HR) for death of 1.2 (99% CI, 0.82–1.76). Previous exposure to platinum did not affect this result.

    • The addition of bevacizumab to combination chemotherapy led to an improvement in OS: 17 months for chemotherapy plus bevacizumab versus 13.3 months for chemotherapy alone (HR, 0.71; 98% CI, 0.54–0.95), and extended PFS: 8.2 months for chemotherapy plus bevacizumab versus 5.9 months for chemotherapy alone, HR, 0.67; (CI, 0.54–0.82).

    • The addition of bevacizumab was well tolerated and showed no difference in quality of life between the two groups.

    • Patients on bevacizumab were more likely to have grade 3 or higher fistulae (6% vs. 0%), and grade 3 or higher thromboembolic events (8% vs. 1%) compared with patients on chemotherapy alone.

    • As a result, the addition of bevacizumab may be considered for this patient population.

Pelvic exenteration

No standard treatment is available for patients with recurrent cervical cancer that has spread beyond the confines of a radiation or surgical field. For locally recurrent disease, pelvic exenteration can lead to a 5-year survival rate of 32% to 62% in selected patients.[20,21] These patients are appropriate candidates for clinical trials testing drug combinations or new anticancer agents.

Treatment Options Under Clinical Evaluation for Recurrent Cervical Cancer

Treatment options under clinical evaluation for recurrent cervical cancer include the following:

  1. New anticancer drugs in phase I and phase II clinical trials.
Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent cervical cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References
  1. Thomas GM, Dembo AJ, Black B, et al.: Concurrent radiation and chemotherapy for carcinoma of the cervix recurrent after radical surgery. Gynecol Oncol 27 (3): 254-63, 1987.  [PUBMED Abstract]

  2. Thigpen JT, Blessing JA, DiSaia PJ, et al.: A randomized comparison of a rapid versus prolonged (24 hr) infusion of cisplatin in therapy of squamous cell carcinoma of the uterine cervix: a Gynecologic Oncology Group study. Gynecol Oncol 32 (2): 198-202, 1989.  [PUBMED Abstract]

  3. Coleman RE, Harper PG, Gallagher C, et al.: A phase II study of ifosfamide in advanced and relapsed carcinoma of the cervix. Cancer Chemother Pharmacol 18 (3): 280-3, 1986.  [PUBMED Abstract]

  4. Sutton GP, Blessing JA, McGuire WP, et al.: Phase II trial of ifosfamide and mesna in patients with advanced or recurrent squamous carcinoma of the cervix who had never received chemotherapy: a Gynecologic Oncology Group study. Am J Obstet Gynecol 168 (3 Pt 1): 805-7, 1993.  [PUBMED Abstract]

  5. McGuire WP, Blessing JA, Moore D, et al.: Paclitaxel has moderate activity in squamous cervix cancer. A Gynecologic Oncology Group study. J Clin Oncol 14 (3): 792-5, 1996.  [PUBMED Abstract]

  6. Verschraegen CF, Levy T, Kudelka AP, et al.: Phase II study of irinotecan in prior chemotherapy-treated squamous cell carcinoma of the cervix. J Clin Oncol 15 (2): 625-31, 1997.  [PUBMED Abstract]

  7. Monk BJ, Sill MW, Burger RA, et al.: Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol 27 (7): 1069-74, 2009.  [PUBMED Abstract]

  8. Buxton EJ, Meanwell CA, Hilton C, et al.: Combination bleomycin, ifosfamide, and cisplatin chemotherapy in cervical cancer. J Natl Cancer Inst 81 (5): 359-61, 1989.  [PUBMED Abstract]

  9. Omura GA, Blessing JA, Vaccarello L, et al.: Randomized trial of cisplatin versus cisplatin plus mitolactol versus cisplatin plus ifosfamide in advanced squamous carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol 15 (1): 165-71, 1997.  [PUBMED Abstract]

  10. Rose PG, Blessing JA, Gershenson DM, et al.: Paclitaxel and cisplatin as first-line therapy in recurrent or advanced squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol 17 (9): 2676-80, 1999.  [PUBMED Abstract]

  11. Burnett AF, Roman LD, Garcia AA, et al.: A phase II study of gemcitabine and cisplatin in patients with advanced, persistent, or recurrent squamous cell carcinoma of the cervix. Gynecol Oncol 76 (1): 63-6, 2000.  [PUBMED Abstract]

  12. Long HJ 3rd, Bundy BN, Grendys EC Jr, et al.: Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol 23 (21): 4626-33, 2005.  [PUBMED Abstract]

  13. Morris M, Blessing JA, Monk BJ, et al.: Phase II study of cisplatin and vinorelbine in squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol 22 (16): 3340-4, 2004.  [PUBMED Abstract]

  14. Tewari KS, Monk BJ: Gynecologic oncology group trials of chemotherapy for metastatic and recurrent cervical cancer. Curr Oncol Rep 7 (6): 419-34, 2005.  [PUBMED Abstract]

  15. Moore DH, Blessing JA, McQuellon RP, et al.: Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol 22 (15): 3113-9, 2004.  [PUBMED Abstract]

  16. Tewari KS, Monk BJ: Recent achievements and future developments in advanced and recurrent cervical cancer: trials of the Gynecologic Oncology Group. Semin Oncol 36 (2): 170-80, 2009.  [PUBMED Abstract]

  17. Monk BJ, Sill MW, McMeekin DS, et al.: Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol 27 (28): 4649-55, 2009.  [PUBMED Abstract]

  18. Cella D, Huang HQ, Monk BJ, et al.: Health-related quality of life outcomes associated with four cisplatin-based doublet chemotherapy regimens for stage IVB recurrent or persistent cervical cancer: a Gynecologic Oncology Group study. Gynecol Oncol 119 (3): 531-7, 2010.  [PUBMED Abstract]

  19. Tewari KS, Sill MW, Long HJ 3rd, et al.: Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med 370 (8): 734-43, 2014.  [PUBMED Abstract]

  20. Alberts DS, Kronmal R, Baker LH, et al.: Phase II randomized trial of cisplatin chemotherapy regimens in the treatment of recurrent or metastatic squamous cell cancer of the cervix: a Southwest Oncology Group Study. J Clin Oncol 5 (11): 1791-5, 1987.  [PUBMED Abstract]

  21. Tumors of the cervix. In: Morrow CP, Curtin JP: Synopsis of Gynecologic Oncology. 5th ed. New York, NY: Churchill Livingstone, 1998, pp 107-151.