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    Cervical Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Stage IVB Cervical Cancer Treatment

    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[4,5,6] 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.[8,12,13,14,15,16]

    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.
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