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Cervical Cancer Treatment (Professional) (cont.)

Recurrent Cervical Cancer

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.[1,2] These patients are appropriate candidates for clinical trials testing drug combinations or new anticancer agents.

The Gynecologic Oncology Group (GOG) has reported on several randomized phase III trials, (GOG-0179, GOG-0240, which is still active) in this setting with only one regimen being superior in overall survival (OS) to single-agent cisplatin administered intravenously at 50 mg/mē every 3 weeks.[3,4] However, incremental progress was made during the initial six randomized GOG trials that failed to reach their primary endpoint of improving survival. They showed that doubling the doses of cisplatin and adding either ifosfamide or paclitaxel to cisplatin increased the response rates and prolonged time to progression but at a cost of added toxicity and no prolongation of OS. The seventh randomized GOG trial in the setting of stage IVB and recurrent cervical cancer showed that adding topotecan at 0.75 mg/mē on the first 3 days of a 21-day cycle to cisplatin prolonged the median survival by 2.9 months (6.5–9.4 months; P = .017) with an unadjusted relative-risk estimate for survival of 0.76 (95% CI, .593–.979; P = .017, one tailed) compared to cisplatin alone. Although the cisplatin/topotecan doublet is associated with more bone marrow suppression compared to cisplatin alone, there was no associated decrement in quality of life found with the combination.[5]

Because it was superior to cisplatin alone in response rates and progression-free survival, patients with performance status of 0 or 1 tolerated the combination in the GOG-selected paclitaxel plus cisplatin (PC) regimen in the standard comparator arm for a subsequent trial with 513 patients comparing four cisplatin-based doublets (P-C vs. gemcitabine-C, vinorelbine-C vs. topotecan-C) in patients with advanced and recurrent cervical carcinoma.[6] This study was closed early because of a futility analysis showing no likely differences to emerge. A full publication is awaited.

Standard treatment options:

  1. For recurrence in the pelvis following radical surgery, radiation therapy in combination with chemotherapy (fluorouracil with or without mitomycin) may cure 40% to 50% of patients.[7]
  2. Chemotherapy can be used for palliation. Tested drugs include the following:
    • Cisplatin (15%–25% response rate).[8]
    • Ifosfamide (15%–30% response rate).[9,10]
    • Paclitaxel (17% response rate).[11]
    • Irinotecan (21% response rate in patients previously treated with chemotherapy).[12]
    • Bevacizumab (11% response rate, 24% survived progression free for at least 6 months; as seen in GOG-0227C).[13]
    • Ifosfamide/cisplatin.[14,15]
    • Paclitaxel/cisplatin (46% response rate).[16]
    • Cisplatin/gemcitabine (41% response rate).[17]
    • Cisplatin/topotecan (27% response rate).[4]
    • Cisplatin/vinorelbine (30% response rate).[18]

Treatment options under clinical evaluation:

  • New anticancer drugs in phase I and phase II clinical trials.

Information about ongoing clinical trials is available from the NCI Web site.

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. 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.
  2. Tumors of the cervix. In: Morrow CP, Curtin JP: Synopsis of Gynecologic Oncology. 5th ed. New York, NY: Churchill Livingstone, 1998, pp 107-151.
  3. Tewari KS, Monk BJ: Gynecologic oncology group trials of chemotherapy for metastatic and recurrent cervical cancer. Curr Oncol Rep 7 (6): 419-34, 2005.
  4. 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.
  5. Monk BJ, Huang HQ, Cella D, et al.: Quality of life outcomes from a randomized phase III trial of cisplatin with or without topotecan in advanced carcinoma of the cervix: a Gynecologic Oncology Group Study. J Clin Oncol 23 (21): 4617-25, 2005.
  6. Monk BJ, Sill M, McMeekin DS, et al.: A randomized phase III trial of four cisplatin (CIS) containing doublet combinations in stage IVB, recurrent or persistent cervical carcinoma: a Gynecologic Oncology Group (GOG) study. [Abstract] J Clin Oncol 26 (Suppl 15): A-LBA5504, 2008.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
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