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Chemotherapy for Recurrent or Persistent Cervical Cancer

The prognosis of advanced cervical cancer is poor. Hopefully, this is a disease that, in the future, will not exist due to regular screenings and vaccinations against strains of human papilloma (HPV). A large randomized trial immunized 2392 women with three doses of a HPV type 16 vaccine vs. three doses of placebo. HPV-16 infection and HPV-16-related cervical intraepithelial neoplasia were significantly reduced in the vaccinated arm. Salvage chemotherapy for recurrent or persistent cervical cancer has not been shown to increase survival. Cisplatin is the drug most commonly used to treat this disease, either in combination with radiation, ifosfamide, or 5-fluorouracil. Sit et al. (this issue) demonstrated a dramatic overall response rate of 60%, with the combination of taxol and carboplatin in a small number of patients who failed radiotherapy or surgery. It is not clear whether carboplatin is as effective as cisplatin; however, its toxicity profile is much more acceptable. Taxol and carboplatin may become an effective regimen to combine with radiation in the treatment of locally advanced unresectable cervical cancer. This regimen needs to be studied in large prospective randomized trials. The number of chemotherapy cycles required for optimum benefit should also be addressed. Within the past few years, at least five clinical trials have shown there is a significantly decreased recurrence rate and increased disease-free survival when cisplatin-containing chemotherapy regimens are employed with radiation compared with radiation alone or radiation combined with less effective chemotherapy regimens for women with stage IB2 to IVA disease. A Gynecologic Oncology Group (GOG) trial was the first to demonstrate a benefit for cisplatin-5-fluorouracil combined with radiation compared with radiation alone for women with locally advanced unresectable disease, but negative paraaortic lymph nodes. Another GOG study concluded that when hydroxyurea was used in the control arm and compared with two aggressive cisplatin-containing chemotherapy regimens, there was considerable benefit to the cisplatin-containing regimens. The Radiation Therapy Oncology Group compared cisplatin and 5-fluorouracil and radiation with extended field irradiation alone and found significant benefit from the combination. The addition of weekly cisplatin to patients undergoing combined modality therapy, including external radiation, intracavitary radiation, and surgery, resulted in prolonged survival. The Southwest Oncology Group also found that concurrent chemotherapy benefited the results achieved with adjuvant radiotherapy after radical hysterectomy. The future of chemoradiation and chemotherapy alone for advanced cervical cancer is being determined