Radiation therapy fails to achieve tumor control in 20% to 65% of patients with advanced cervical cancer. Chemotherapy, despite its relative lack of success in treating patients with cervical cancer, was evaluated as neoadjuvant treatment in combination with surgery. Concomitant use of chemotherapy and radiation was studied extensively by the GOG and results of five randomized studies were reported. The concept of chemoradiation encompasses the benefits of systemic chemotherapy with the benefits of regional radiation therapy. The use of chemotherapy to sensitize cells to radiation therapy improved local–regional control. These new results changed the way cervical cancer is treated in many medical centers.
An Intergroup trial involving the GOG, the Southwestern Oncology Group, and the Radiation Therapy Oncology Group evaluated postoperative chemoradiation therapy in patients with stage IA2, IB, or IIA cervical cancer who had positive pelvic lymph nodes, positive parametrial extension, or positive vaginal margins at the completion of radical hysterectomy (127). A total of 243 patients were assessed in this trial, with 127 receiving chemoradiation (cisplatin, 5-ﬂuorouracil [5-FU], radiation therapy) and 116 receiving radiation. The results of this trial showed a statistically significant improvement in progression-free survival and overall survival at 43 months for the patients receiving concurrent chemoradiation. The 4-year survival rates for the patients receiving chemoradiation versus radiation alone were 81% and 71%, respectively. The toxicity levels in the two groups were acceptable, with a higher rate of hematologic toxicity in the concurrent chemoradiation arm. This study showed that in patients with these high-risk factors after radical hysterectomy for stage IA2, IB, and IIA disease, chemoradiation is the postoperative treatment of choice.
Concurrent chemoradiation was evaluated in patients with advanced cervical carcinoma. GOG protocol 85 was a prospective study that enrolled patients with stage IIb to IVA cervical cancer and compared concurrent chemoradiation (129). There were 177 patients treated with cisplatin, 5-FU, and radiation. These patients were compared with 191 patients treated with hydroxyurea and radiation. The median follow-up of patients who were alive at the time of the analysis was 8.7 years. Patients who received concurrent chemoradiation and were treated with cisplatin and 5-FU had a statistically significant improvement in progression-free interval and overall survival (129). Hematologic toxicity levels in the two groups were similar. This study showed that cisplatin-based concurrent chemoradiation was a superior treatment when compared with hydroxyurea and concurrent radiation.
GOG Protocol 120 was initiated to evaluate patients with negative para-aortic nodes and cervical carcinoma stage IIB to IVA treated with concurrent chemoradiation. The treatment arms in this study consisted of radiation plus weekly cisplatin; or cisplatin, 5-FU, and hydroxyurea; or hydroxyurea. There were 176 patients in the weekly cisplatin arm; 173 patients in the cisplatin, 5FU, and hydroxyurea arm; and 177 patients in the hydroxyurea arm (130). The two treatment arms with cisplatin-based chemotherapy and radiation showed an improvement in progression-free interval and overall survival at a median follow-up of 35 months. The relative risks for progression of disease or death were 0.55 and 0.57, respectively, for patients treated with cisplatin-based chemotherapy and radiation, compared with the patients treated with hydroxyurea and radiation (130). This study confirmed the findings of GOG Protocol 85 and reaffirmed the finding that cisplatin-based concurrent chemoradiation is the treatment of choice for patients with advanced-stage cervical cancer.