SAN FRANCISCOA major intergroup phase III study reported at the 30th Annual Meeting of the Society of Gynecologic Oncologists has shown that adding chemotherapy to radiation therapy improves the overall survival rate for women with high-risk early-stage cervical cancer. William A. Peters III, MD, of the Puget Sound Oncology Consortium, Seattle, reported the results on behalf of researchers from the Southwest Oncology Group, Gynecologic Oncology Group, and Radiation Therapy Oncology Group.
We were looking at patients who had early, operable cervical cancer but with high-risk features. About 40% of such patients will have disease recurrence, Dr. Peters said in an interview. We were trying to determine whether the addition of systemic chemotherapy would decrease that failure rate. Previous studies had shown that radiation therapy decreased recurrence rates but did not improve long-term survival.
Radical hysterectomy with pelvic lymphadenectomy is the recommended surgical treatment for women diagnosed with early-stage cervical carcinoma. Radiation therapy is usually added for those who have positive lymph nodes or parame-trial involvement. Five-year survival is 80% to 90% in patients without any lymph node or parametrial involvement but drops to 50% to 70% when these risk factors are present.
The study enrolled 260 patients with clinical stage IA2, IB, and IIA carcinoma of the cervix. All were initially treated with radical hysterectomy and pelvic lymphadenectomy and had positive pelvic lymph nodes and/or positive margins and/or microscopic involvement of the parametrium. Of these patients, 241 were evaluable at the time of this report.
Patients were randomized to receive radiation therapy or radiation therapy plus chemotherapy. Patients in each group received 4,930 cGy in 29 fractions to a standard pelvic field.
Chemotherapy consisted of bolus cisplatin(Drug information on cisplatin) (Platinol), 70 mg/m², and a 96-hour infusion of fluorouracil(Drug information on fluorouracil) (5-FU), 1,000 mg/m²/day for 4 days every 3 weeks for four cycles, with the first and second cycles given concurrently with radiation. Both agents are active in cervical cancer, and both are radiation sensitizers.
Progression-free and overall survival were significantly improved in the patients given chemotherapy (P = .01 for each). The hazard ratio for overall survival was 2.02 for the radiation-only arm compared with the radiation/chemotherapy arm. Projected progression-free survival at 4 years was 63% with radiation and 81% with radiation/chemotherapy.
Grade 3-4 hematologic and gastrointestinal toxicity were more frequent in the radiation therapy plus chemotherapy group, Dr. Peters said, but there were no toxicity-related deaths in either group.
For high-risk patients who have positive nodes after radical hysterectomy and/or parametrial involvement and/or positive margins, this study clearly showed a reduction of about 50% in the treatment failure rate. It would be hard to justify treating such patients any other way, based on current knowledge, he said.
The study was one of five cited by the NCI in its recommendation that oncol-ogists use chemotherapy and radiation therapy rather than radiation alone to treat invasive cervical cancer.
Dr. Peters emphasized that the majority of patients who have surgery for cervical cancer do not need adjuvant therapy, only those with risk factors. The regimen is well tolerated and could potentially be used in any high-risk patient who is a candidate for surgery. He noted that this approach could be used in virtually any center that offers radiation therapy and chemotherapy, since it does not require brachytherapy.
The mechanism of action underlying the benefit produced by adding chemotherapy requires further study. Dr. Peters said it could be due to radiation sensitization, a systemic antitumor effect, or a combination of the two.