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Previous Volume 340:1144-1153 April 15, 1999 Number 15 Next

	Full Text PDF Editorial by Thomas, G. M. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited Related Article PubMed Citation

ABSTRACT

Background and Methods On behalf of the Gynecologic Oncology Group, we performed a randomized trial of radiotherapy in combination with three concurrent chemotherapy regimens — cisplatin alone; cisplatin, fluorouracil, and hydroxyurea; and hydroxyurea alone — in patients with locally advanced cervical cancer. Women with primary untreated invasive squamous-cell carcinoma, adenosquamous 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 millimeter, a platelet count of at least 100,000 per cubic millimeter, a serum creatinine level no higher than 2 mg per deciliter (177 µmol per liter), and adequate hepatic function. All patients received external-beam radiotherapy according to a strict protocol. Patients were randomly assigned to receive 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 square meter given as a 96-hour infusion on days 1 and 29, and 2 g of oral hydroxyurea per square meter twice weekly for six weeks (group 2); or 3 g of oral hydroxyurea per square meter twice weekly for six weeks (group 3).

Results The analysis included 526 women. The median duration of follow-up was 35 months. Both groups that received cisplatin had a higher rate of progression-free survival than the group that received hydroxyurea alone (P<0.001 for both comparisons). The relative risks of progression of disease or death were 0.57 (95 percent confidence interval, 0.42 to 0.78) in group 1 and 0.55 (95 percent confidence interval, 0.40 to 0.75) in group 2, as compared with group 3. The overall survival rate was significantly higher in groups 1 and 2 than in group 3, with relative risks of death of 0.61 (95 percent confidence interval, 0.44 to 0.85) and 0.58 (95 percent confidence interval, 0.41 to 0.81), respectively.

Conclusions Regimens of radiotherapy and chemotherapy that contain cisplatin improve the rates of survival and progression-free survival among women with locally advanced cervical cancer.

Source Information

From the Division of Gynecologic Oncology, Department of Reproductive Biology, University Hospitals of Cleveland and Case Western Reserve University, Cleveland (P.G.R.); the Gynecologic Oncology Group, Roswell Park Cancer Institute, Buffalo, N.Y. (B.N.B.); the Radiation Oncology Service, Walter Reed Army Medical Center, Washington, D.C. (E.B.W.); the Division of Oncology, Department of Medicine, University of Mississippi School of Medicine, Jackson (J.T.T.); the Division of Gynecologic Oncology, Hutzel Hospital and Wayne State University, Detroit (G.D.); the Division of Gynecologic Oncology, State University of New York Health Science Center at Brooklyn, Brooklyn (M.A.M.); the Division of Gynecologic Oncology, Duke University School of Medicine, Durham, N.C. (D.L.C.-P.); and the Department of Pathology, University of Washington, Seattle, and the Department of Pathology, Multicare Medical Center, Tacoma, Wash. (S.I.).

Address reprint requests to Denise Mackey at the GOG Administrative Office, Suite 1945, 1234 Market St., Philadelphia, PA 19107, or at dmackey{at}acog.org.

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• Pearcey, R. G., Mohamed, I. G., Hanson, J., Piver, M. S., Morris, M., Eifel, P. J., Rose, P. G., Bundy, B. N. (1999). Treatment of High-Risk Cervical Cancer. NEJM 341: 695-697 [Full Text]  
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• (1999). Concurrent Chemotherapy and Radiotherapy for Advanced Cervical Cancer. JWatch General 1999: 3-3 [Full Text]  
• Keys, H. M., Bundy, B. N., Stehman, F. B., Muderspach, L. I., Chafe, W. E., Suggs, C. L., Walker, J. L., Gersell, D. (1999). Cisplatin, Radiation, and Adjuvant Hysterectomy Compared with Radiation and Adjuvant Hysterectomy for Bulky Stage IB Cervical Carcinoma. NEJM 340: 1154-1161 [Abstract] [Full Text]  
• Thomas, G. M. (1999). Improved Treatment for Cervical Cancer -- Concurrent Chemotherapy and Radiotherapy. NEJM 340: 1198-1200 [Full Text]  
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