Concurrent Chemoradiation for Cervical Cancer

The current practice of treating cervical cancer with surgery or radiation alone has been challenged by the recent information from the National Cancer Institute regarding concurrent chemoradiation for cervical cancer. Results from each of five randomized phase III trials show an overall survival advantage of 30% — plus acceptable toxicity — for cisplatin-based therapy given concurrently with radiation therapy (Table). The patient populations in these studies included women with FIGO stages IB2-IVA cervical cancer treated with primary radiotherapy and women with FIGO stage I-IIA disease with poor prognostic factors (metastatic disease in pelvic lymph nodes, parametrial disease, or positive surgical margins) at the time of primary surgery. Although the trials varied in terms of stage of disease, dose of radiation, and schedule of cisplatin and radiation, they all demonstrated significant survival benefit for this combined approach. The risk of death from cervical cancer was decreased by 30% to 50% with concurrent chemoradiation. Based on these results, strong consideration should be given to the incorporation of concurrent cisplatin-based chemotherapy with radiation therapy in women who require radiation therapy for treatment of cervical cancer.

The Radiation Therapy Oncology Group Protocol 9001² included stages IIB, III, and IVA and randomized 389 patients to (1) external beam (pelvis) and intracavitary radiation therapy with 5-FU infusion and cisplatin or (2) extended-field external beam (pelvis and para-aortic) and intracavitary radiation therapy. The three-year survival rate for women on the cisplatin/5-FU arm is 75% compared to 63% for women on the extended-field radiation-only arm.

The Gynecologic Oncology Group Protocol 120³ included stages IIB, III, and IVA and randomized 526 patients to (1) external beam (pelvis) and intracavitary radiation with weekly cisplatin or (2) external beam (pelvis) and intracavitary radiation with 5-FU, cisplatin, and hydroxyurea or (3) external beam (pelvis) and intracavitary radiation with hydroxyurea. The three-year survival rate for women on both the weekly cisplatin/radiation arm and the 5-FU/cisplatin/hyroxyurea arm is 65% compared to 47% for women on the hydroxyurea/radiation arm.

The Southwest Oncology Group Protocol 8797⁴ included stages IA2, IB, and IIA and randomized 243 patients to (1) external beam (pelvis) radiation therapy with cisplatin and 5-FU infusion or (2) external beam (pelvis) radiation therapy. The three-year survival rate for women on the adjuvant cisplatin/5-FU plus radiation arm is 87% compared to 77% for women on the adjuvant radiation alone arm.

The Gynecologic Oncology Group Protocol 123⁵ included bulky stage IB and randomized 368 patients to (1) external beam (pelvis) and intracavitary radiation with weekly cisplatin, followed by extrafascial hysterectomy or (2) external beam (pelvis) and intracavitary radiation followed by extrafascial hysterectomy. The survival rate for women treated with cisplatin chemotherapy is 83% compared to 74% of those treated with radiotherapy alone.

Adjuvant or definitive radiotherapy is widely used to treat women with locally and regionally advanced cervical cancer. These five randomized phase III trials demonstrate that platinum-based chemotherapy, when given concurrently with radiotherapy, prolongs survival in women with locally advanced cervical cancer, stages IB-IVA, as well as in women with stage I-IIA disease found to have metastatic disease in the pelvic lymph nodes, positive metastatic parametrial disease, or positive surgical margins at the time of primary surgery. Concurrent cisplatin-based chemoradiation reduced the risk of recurrence by 30% to 50% across a spectrum of treatment prescriptions.

While an optimal chemotherapy regimen has not been established, significant results were seen using cisplatin alone or in combination with 5-FU or 5-FU/hydroxyurea. Long-term toxicity data are incomplete on some of these trials, but to date all these regimens appear tolerable. Acute toxicities vary among the regimens, as do the doses and schedules of drugs and radiation.