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 [NCT00003945], GOG-0240 [NCT00803062]) in this setting. Single-agent cisplatin administered intravenously at 50 mg/m² every 3 weeks was the most-used regimen to treat recurrent cervical cancer since it was initially introduced in the 1970s.[3,4]
Various combinations containing cisplatin [3,4] failed to reach their primary endpoint of improving survival, however, a doubling of the cisplatin dose-rate did improve survival. Combinations with paclitaxel and with ifosfamide improved response rates (RR), but they did so at a cost of much greater toxicity, especially with the latter drug. A survival advantage over cisplatin was obtained with the cisplatin + topotecan (CT) doublet  leading to approval of this indication for topotecan by the Food and Drug Administration. However, in this study, cisplatin underperformed because many patients had received this drug earlier as a radiosensitizer. (Refer to Stages IIA, IIB, III, and IVA for more information on chemoradiation and the drug cisplatin, in particular.). Therefore, cisplatin plus paclitaxel (CP) was chosen as the reference arm in GOG-0204 (NCT00064077).
The GOG has reported on sequential randomized trials dealing with chemotherapy for stage IVB, recurrent, or persistent cervical cancer.[4,5,6,7,8] In the initial trial, the primary endpoint of exceeding the survival observed with cisplatin alone was not reached. However, in these trials:
- The ifosfamide + cisplatin combination was superior to cisplatin alone in the secondary endpoint of RR but at the cost of increased toxicity.
- The paclitaxel + cisplatin (PC) combination, similarly, was superior in RR and progression-free survival (PFS), and its toxicity was similar to the single agent except in patients with GOG performance status 2 (scale: 0, asymptomatic–4, totally bedridden).
- The CT doublet combination had a significant advantage in overall survival (OS) compared with cisplatin alone, but cisplatin alone underperformed in this trial because as many as 40% of the patients had already received cisplatin up front as a radiosensitizer.