Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer

Background and Methods On behalf of the Gynecologic Oncology Group, we perf ormed a randomized trial of radiotherapy in combination with three concurre nt chemotherapy regimens - cisplatin alone; cisplatin, fluorouracil, and hy droxyurea; and hydroxyurea alone - in patients with locally advanced cervic al cancer. Women with primary untreated invasive squamous-cell carcinoma, a denosquamous carcinoma, or adenocarcinoma of the cervix of stage IIB, III, or IVA, without involvement of the para-aortic lymph nodes, were enrolled. The patients had to have a leukocyte count of at least 3000 per cubic milli meter, a platelet count of at least 100,000 per cubic millimeter, a serum c reatinine level no higher than 2 mg per deciliter (177 mu mol per liter), a nd adequate hepatic function. All patients received external-beam radiother apy according to a strict protocol. Patients were randomly assigned to rece ive one of three chemotherapy regimens: 40 mg of cisplatin per square meter of body-surface area per week for six weeks (group 1); 50 mg of cisplatin per square meter on days 1 and 29, followed by 4 g of fluorouracil per squa re meter given as a 96-hour infusion on days 1 and 29, and 2 g of oral hydr oxyurea per square meter twice weekly for six weeks (group 2); or 3 g of or al hydroxyurea per square meter twice weekly for six weeks (group 3). Results The analysis included 526 women. The median duration of follow-up w as 35 months. Both groups that received cisplatin had a higher rate of prog ression-free survival than the group that received hydroxyurea alone (P<0.0 01 for both comparisons). The relative risks of progression of disease or d eath were 0.57 (95 percent confidence interval, 0.42 to 0.78) in group 1 an d 0.55 (95 percent confidence interval, 0.40 to 0.75) in group 2, as compar ed with group 3. The overall survival rate was significantly higher in grou ps 1 and 2 than in group 3, with relative risks of death of 0.61 (95 percen t confidence interval, 0.44 to 0.85) and 0.58 (95 percent confidence interv al, 0.41 to 0.81), respectively. Conclusions Regimens of radiotherapy and chemotherapy that contain cisplati n improve the rates of survival and progression-free survival among women w ith locally advanced cervical cancer. (N Engl J Med 1999;340:1144-53.) (C)1 999. Massachusetts Medical Society.