Chemotherapy for Advanced Disease Chemotherapy was studied in advanced cervical cancer with mixed results. Single-agent chemotherapy was the standard for advanced or recurrent disease. Active agents include cisplatin, carboplatin, paclitaxel, and ifosfamide, but response rates are only 10% to 20% with a median duration of only 4 to 6 months. A number of trials were performed to determine whether multiagent chemotherapy is superior. The GOG Protocol 149 studied patients with histologically confirmed, advanced stage (IVb), recurrent or persistent squamous cell cancer of the cervix and randomized these patients to one of two combination chemotherapy treatment arms. Of the 287 patients, 146 patients were randomized to the cisplatin and ifosfamide arm, and 141 patients received cisplatin, ifosfamide, and bleomycin. There were no differences in overall survival, progression-free survival, response rates, or overall toxicity between the two combination chemotherapy regimens (149). In another trial sponsored by the GOG, single-agent cisplatin was compared to cisplatin plus either dibromodulcitol or ifosfamide plus mesna. In this trial, the combination of cisplatin plus ifosfamide had a better response rate (31% vs. 18%) and median time to progression (4.6 months vs. 3.2 months) compared with single agent cisplatin. Toxicity was notably higher in the combination regimen, and there was no overall survival advantage demonstrated (150). The GOG published the results of a study comparing single-agent cisplatin to cisplatin plus paclitaxel in women with stage IVb squamous cell cancer of the cervix. Although the response rate (36% vs. 19%) and progression-free survival (4.8 months vs. 2.8 months) were greater for the combination regimen, there was only a 1-month increase in overall survival (151). Finally, the regimen of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), which received considerable attention because of preliminary studies suggesting high response rates, was evaluated in POG Protocol 179. In this study,
MVAC was compared to cisplatin alone, and cisplatin combined with topotecan. The MVAC arm was prematurely closed because of excessive toxicity, and the remaining cisplatin arms were compared. Although the combination of cisplatin and topotecan was superior to cisplatin alone, the improvement in overall survival was only 3 months. The combination arm had a higher complete response rate, overall response rate, progression-free survival, and overall survival (152). Doublet therapy with cisplatin and paclitaxel is considered standard therapy based on GOG 204, which analyzed four cisplatin-containing doublets (topotecan, paclitaxel, vinorelbine, and gemcitabine) for the best efficacy; although no major differences existed in overall survival for the four doublets, the cisplatin and paclitaxel doublet trended toward the best results (153). Overall, it appears that multiagent regimens offer an improved response rate and slightly higher overall survival but with increased toxicity. Other studies showed comparable survival and less toxicity with carboplatin and paclitaxel (154).
Treatment of Cervical
Stage IA Until 1985, no FIGO recommendation existed concerning the size of lesion or the