Early studies of radiation sensitization involved comparisons of cisplatin and 5-fluor-ouracil and radiation therapy with hydroxyurea and radiation therapy carried out by the Gynecologic Oncology Group (GOG) for treatment of stages IIB to IVA disease (133,134). There have been several clinical trials testing cisplatin or cisplatin-based regimens with radiation therapy in locally advanced cervix cancer (135). A phase II trial of more than 70 patients with stage IB (bulky) to IVA cervix cancer received radiation therapy (external beam plus low-dose-rate brachytherapy) along with cisplatin to provide radiosensitization and optimize the dose intensity of the cisplatin (136-138). The cisplatin dose was 20 mg/m2/d x 5 every 3 wk to a total dose of 400 mg/m2. Radiation therapy was designed to deliver 80 Gy to point A and 55 Gy to point B. In the initial follow-up report 91% of patients had complete responses. At 4 yr, more than 75% of stage IB to IIB patients were alive; however, only 25% of patients with stage III disease were alive with no plateau seen on the curve. Amifostine has been studied as a normal tissue protector with cisplatin and radiation therapy for treatment of locally advanced cervical cancer (135). The results of three phase II clinical trials have recently been reported showing an improvement in local control and survival in cervical cancer patients after concomitant cisplatin and radiotherapy (139-141). Santin et al. (142) examined the
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4. Local control and survival in inoperable lung cancer patients treated with RT alone, weekly cisplatin or daily cisplatin (155).
effect of therapy on the immune system of cervical cancer patients undergoing external irradiation and intracavity brachytherapy with or without concurrent cisplatin and found that administration of concurrent cisplatinum with radiation therapy may have synergis-tically increased cytotoxic effects of radiation on tumor cells but did not alter the magnitude or characteristics of the radiation-induced immunosuppression. The role of concurrent radiation therapy and chemotherapy consisting of 5-fluorouracil and cisplatin was explored in the treatment of local-regionally advanced vulvar cancer and results appeared positive (143). The combination of cisplatin or carboplatin and radiation therapy has been discussed for locally advanced prostate cancer (144). Kaufman et al. (145) conducted a study of 34 patients to assess the safety, tolerance, and efficacy of transurethral surgery plus concomitant cisplatin, 5-fluorouracil, and radiation therapy in conjunction with selective bladder preservation in patients with muscle-invading bladder cancer. This protocol included high-dose hypofractionated radiation therapy and had a 67% complete response rate to induction therapy and a 66% three-year survival rate with an intact bladder.
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