Combined-modality therapy of locally advanced cervical cancer

Six randomized trials of chemoradiotherapy in cervical cancer have demonstrated improvement with cisplatin-based chemoradiotherapy compared with radiation alone or radiation with hydroxyurea. Only one randomized trial (Gynecologic Oncology Group [GOG] 120) compared different cisplatin-based regimens and demonstrated significantly more hematologic and gastrointestinal toxic effects with the combination of cisplatin, fluorouracil, and hydroxyurea than with weekly cisplatin alone. The use of fluorouracil and mitomycin as radiation sensitizers for cervical cancer is based on their activity in chemoradiotherapy for anal carcinoma. However, a three-fold increase in serious late bowel toxicity was seen in patients treated with fluorouracil and mitomycin compared with fluorouracil alone when combined with radiation therapy for cervical cancer. Another randomized trial demonstrated improvement in survival with fluorouracil infusion compared with radiation alone only in early-stage disease. However, the most recently completed randomized trial by the GOG, which compared continuous fluorouracil infusion with weekly cisplatin, was closed when interim analysis demonstrated no potential superiority to the fluorouracil arm. Uncontrolled studies have evaluated the use of carboplatin on several different schedules, but no controlled trials have yet been performed. In metastatic and recurrent cervical cancer, a number of newer agents, including paclitaxel, gemcitabine, topotecan, and vinorelbine, have demonstrated modest single-agent activity and even greater activity in combination with cisplatin. An expanding series of trials will define the role of these new agents combined with cisplatin and radiation therapy for locally advanced cervical cancer. The potential role of biologic agents in combination with chemoradiotherapy also needs to be examined in locally advanced cervical cancer.