This study investigated the addition of cisplatin-based chemotherapy to standard postoperative radiation therapy in the treatment of women at high risk of recurrence after radical hysterectomy for cervical cancer. Two hundred forty-three patients with stage IA, IB, or IIA carcinoma of the cervix who had pelvic lymph node metastases, parametrial tumor infiltration, or a positive surgical margin at the time of radical hysterectomy were randomly assigned to receive pelvic radiation therapy (N = 116) or pelvic radiation therapy plus four cycles of chemotherapy (N = 127) after type 3 radical hysterectomy with pelvic lymphadenectomy. Radiation therapy in both groups consisted of 49.3 Gy in 29 factions delivered to a standard pelvic field over 6 weeks. Adjunctive chemotherapy was started on day 1 of radiation treatment. Cisplatin was administered intravenously over 2 hours at a dose of 70 mg/m2 on day 1, followed by 4 days of continuous infusion of 100 mg/m2 5-fluorouracil. The two treatment groups were similar in clinical and demographic characteristics.
In each treatment group, approximately 10 percent of patients received <45 Gy radiation. For those who received at least 45 GY, the median time to completion of radiation therapy was 41 days for the radiation-only group and 43 days for the radiation plus chemotherapy group. Seventy-one percent of the women receiving chemotherapy completed at least three cycles of treatment.
After a median follow up of 42 months, the patients who received both radiation and chemotherapy had an estimated 4-year progression-free survival rate of 80 percent, compared with 63 percent in women treated with radiation alone (P = .003). The estimated 4-year overall survival rates for these two groups were 81 and 71 percent, respectively (P = .007). Multivariate analysis found only lesion size to be a significant predictor of progression-free survival or overall survival (P = .05 and .03, respectively). Although patients in the chemotherapy group had fewer recurrences, the pattern of recurrence was similar in both groups.
Patients with adenocarcinoma or adenosquamous carcinoma who were treated with radiation alone had a worse survival rate than those with squamous tumors treated with radiation alone. However, there was no difference in survival rates among cell types in the group treated with radiation plus chemotherapy. An analysis of the women receiving chemotherapy found that higher numbers of completed chemotherapy cycles were associated with greater progression-free survival and overall survival rates (P = .03 for both). Twenty-one women in the chemotherapy group developed grade 4 toxicity that was associated with treatment. Most episodes were hematologic. Four patients in the radiation alone group experienced grade 4 toxicity.
J Clin Oncol 2000;18:1606–1613