Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma

Background Bulky stage IB cervical cancers have a poorer prognosis than sma ller stage I cervical cancers. For the Gynecologic Oncology Group, we condu cted a trial to determine whether weekly infusions of cisplatin during radi otherapy improve progression-free and overall survival among patients with bulky stage IB cervical cancer. Methods Women with bulky stage IB cervical cancers (tumor, greater than or equal to 4 cm in diameter) were randomly assigned to receive radiotherapy a lone or in combination with cisplatin (40 mg per square meter of body-surfa ce area once a week for up to six doses; maximal weekly dose, 70 mg),follow ed in all patients by adjuvant hysterectomy. Women with evidence of lymphad enopathy on computed tomographic scanning or lymphangiography were ineligib le unless histologic analysis showed that there was no lymph-node involveme nt. The cumulative dose of external pelvic and intracavitary radiation was 75 Gy to point A (cervical parametrium) and 55 Gy to point B (pelvic wall). Cisplatin was given during external radiotherapy, and adjuvant hysterectom y was performed three to six weeks later. Results The relative risks of progression of disease and death among the 18 3 women assigned to receive radiotherapy and chemotherapy with cisplatin, a s compared with the 186 women assigned to receive radiotherapy alone, were 0.51 (95 percent confidence interval, 0.34 to 0.75) and 0.54 (95 percent co nfidence interval, 0.34 to 0.86), respectively. The rates of both progressi on-free survival (P<0.001) and overall survival (P=0.008) were significantl y higher in the combined-therapy group at four years. In the combined-thera py group there were higher frequencies of transient grade 3 (moderate) and grade 4 (severe) adverse hematologic effects (21 percent, vs. 2 percent in the radiotherapy group) and adverse gastrointestinal effects (14 percent vs . 5 percent). Conclusions Adding weekly infusions of cisplatin to pelvic radiotherapy fol lowed by hysterectomy significantly reduced the risk of disease recurrence and death in women with bulky stage IB cervical cancers. (N Engl J Med 1999 ;340:1154-61.) (C)1999, Massachusetts Medical Society.