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Cervical Cancer Treatment (PDQ®)

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Stage IVB Cervical Cancer Treatment

Standard Treatment Options for Stage IVB Cervical Cancer
        Palliative radiation therapy
        Palliative chemotherapy
Cisplatin in combination with other drugs
Treatment Options Under Clinical Evaluation for Stage IVB Cervical Cancer
Current Clinical Trials



Standard Treatment Options for Stage IVB Cervical Cancer

Standard treatment options for stage IVB cervical cancer include the following:

  1. Palliative radiation therapy.
  2. Palliative chemotherapy.
Palliative radiation therapy

Radiation therapy may be used to palliate central disease or distant metastases.

Palliative chemotherapy

Multiple agents are associated with objective response rates, however, durable responses are rare.

Drugs used in stage IVB cervical cancer treatment are shown in Table 6.

Table 6. Drugs Used to Treat Stage IVB Cervical Cancer
Drug Name Response Rate 
Cisplatin [1,2]15%–25%
Ifosfamide [3]31%
Paclitaxel [4-6]17%
Ifosfamide/cisplatin [7,8]31%
Irinotecan [9]21% in patients previously treated with chemotherapy
Paclitaxel/cisplatin [10]46%
Cisplatin/gemcitabine [11]41%
Cisplatin/topotecan [12]27%

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 stages IVB, recurrent, or persistent cervical cancer.[8,12-16]

Evidence (cisplatin in combination with other drugs):

  1. GOG-110, GOG-0179, GOG-0169:
    • 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, 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:[16]
    • 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 response rates, 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,[16] but none of the patients in the study arms differed in health-related quality of life during treatment.[17] However, there were more neurologic side effects for PC.

  3. GOG-0240 (NCT00803062) was designed to answer the following two questions:[18]
    • Can a nonplatinum combination show improvement over the standard of cisplatin-paclitaxel in this population that was previously treated with cisplatin during radiation therapy?

    • Can the addition of bevacizumab improve combination chemotherapy in patients with stages 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) 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.

Treatment Options Under Clinical Evaluation for Stage IVB Cervical Cancer

Treatment options under clinical evaluation for stage IVB 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 stage IVB 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. 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]

  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. Kudelka AP, Winn R, Edwards CL, et al.: Activity of paclitaxel in advanced or recurrent squamous cell cancer of the cervix. Clin Cancer Res 2 (8): 1285-8, 1996.  [PUBMED Abstract]

  5. Thigpen T, Vance RB, Khansur T: The platinum compounds and paclitaxel in the management of carcinomas of the endometrium and uterine cervix. Semin Oncol 22 (5 Suppl 12): 67-75, 1995.  [PUBMED Abstract]

  6. 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]

  7. 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]

  8. 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]

  9. 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]

  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. 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]

  14. 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]

  15. 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]

  16. 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]

  17. 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]

  18. 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]