Long-Term Follow-Up of a Randomized Trial Comparing Concurrent Single Agent Cisplatin, Cisplatin-Based Combination Chemotherapy, or Hydroxyurea During Pelvic Irradiation for Locally Advanced Cervical Cancer: A Gynecologic Oncology Group Study

PURPOSE We report the long-term survival and toxicity of a randomized phase III study comparing cisplatin alone with cisplatin, flurouracil, and hydroxyurea versus hydroxyurea concurrent with pelvic irradiation for patients with locally advanced cervical cancer with pathologically negative para-aortic nodes. PATIENTS AND METHODS Comparisons of progression-free (PFS) and overall survival (OS) between treatment arms utilized Kaplan-Meier and log-rank statistics. Relative risk estimates adjusting for prognostic factors were determined using the Cox proportional hazards regression model. Pearson's 2 test was used to assess differences in adverse events. RESULTS The analysis included 526 patients. The median follow-up among surviving patients was 106 months. Consistent with the original report, improvement in PFS and OS was evident for both cisplatin-containing arms compared with hydroxyurea (P < .001). Analogous results were seen for stage IIB and for stage III disease (each P < .025). The relative risk of progression of disease or death was 0.57 (95% CI, 0.43 to 0.75) with cisplatin and 0.51 (95% CI, 0.38 to 0.67) with cisplatin-based combination chemotherapy compared with hydroxyurea. Among 518 patients who received radiation, acute (grade 3 or 4) gastrointestinal or urologic toxicities occurred in 66 with cisplatin (19.1%) and 29 with hydroxyurea (16.8%). Delayed radiation toxicity occurred in six patients who received cisplatin (1.7%) and two who received hydroxyurea (1.2%; P = .680). CONCLUSION Cisplatin-based chemotherapy during pelvic radiation therapy improves long-term PFS and OS among locally advanced cervical cancer patients collectively and for stage IIB and III disease, individually. There was no observed increase in late toxicity with cisplatin-based chemoradiotherapy.

[1]  D. Cox.  Regression Models and Life-Tables , 1972 .

[2]  B N Bundy,et al.  Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. , 1999, The New England journal of medicine.

[3]  P. Disaia,et al.  Extraperitoneal versus transperitoneal selective paraaortic lymphadenectomy in the pretreatment surgical staging of advanced cervical carcinoma (a Gynecologic Oncology Group study) , 1989, Gynecologic oncology.

[4]  P J Eifel,et al.  Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. , 1999, The New England journal of medicine.

[5]  J. Cooper,et al.  Radiotherapy with or without misonidazole for patients with stage IIIB or stage IVA squamous cell carcinoma of the uterine cervix: preliminary report of a Radiation Therapy Oncology Group randomized trial. , 1987, International journal of radiation oncology, biology, physics.

[6]  B N Bundy,et al.  Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  B. Bundy,et al.  Hydroxyurea versus misonidazole with radiation in cervical carcinoma: long-term follow-up of a Gynecologic Oncology Group trial. , 1993, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  G. Hanks,et al.  Patterns of radiotherapy practice for patients with squamous carcinoma of the uterine cervix: patterns of care study , 1997 .

[9]  Mitchell Morris,et al.  Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irradiation for high-risk cervical cancer: an update of radiation therapy oncology group trial (RTOG) 90-01. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  B N Bundy,et al.  Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. , 1999, The New England journal of medicine.

[11]  C. Perez,et al.  Radiation therapy alone in the treatment of carcinoma of the uterine cervix: a 20-year experience. , 1986, Gynecologic oncology.

[12]  P. Grigsby,et al.  The clinical implications of hydronephrosis and the level of ureteral obstruction in stage IIIB cervical cancer. , 1998, International journal of radiation oncology, biology, physics.

[13]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[14]  A. Fyles,et al.  A randomized trial of standard versus partially hyperfractionated radiation with or without concurrent 5-fluorouracil in locally advanced cervical cancer. , 1998, Gynecologic oncology.

[15]  G. Thomas,et al.  Concurrent chemotherapy and radiation for locally advanced cervical cancer: the new standard of care. , 2000, Seminars in radiation oncology.

[16]  P. Disaia,et al.  Carcinoma of the cervix treated with radiation therapy I. A multi‐variate analysis of prognostic variables in the gynecologic oncology group , 1991, Cancer.