Trial Information

A Randomized Comparison of Radiation vs Radiation Plus Weekly Cisplatin vs Radiation Plus PVI (Protracted Venous Infusion) 5-FU in Patients With Stage II-B, III-B, and IV-A Carcinoma of the Cervix With Negative Paraaortic Nodes

OBJECTIVES: I. Compare the progression-free survival and survival of patients with advanced
cervical cancer limited to the pelvis receiving either radiotherapy alone, or radiotherapy
plus weekly cisplatin, or radiotherapy plus prolonged venous infusion (PVI) of fluorouracil.
[Radiotherapy alone regimen closed 8/18/98] II. Determine the relative toxic effects of
radiation therapy plus chemotherapy with either weekly cisplatin or PVI fluorouracil
compared to radiation alone. [Radiotherapy alone regimen closed 8/18/98] IV. Compare the
progression-free survival and survival of patients with advanced cervical cancer limited to
the pelvis and who smoke at the time of diagnosis versus non-smokers and those who smoke
during radiation therapy versus those who quit.

OUTLINE: This is a randomized study. Patients are stratified by stage, performance of
para-aortic lymphadenectomy, and brachytherapy method (HDR vs LDR). Prior to treatment
patients complete a questionnaire regarding past and present smoking history and exposure to
secondhand smoke. In arm I, patients undergo external radiation therapy to the pelvis once
daily 5 times a week for 5 weeks. Then, patients receive either low dose rate or high dose
rate intracavitary brachytherapy in one or two applications or 5 fractions once or twice a
week, respectively. If intracavitary radiation therapy cannot be performed, then shrinking
field technique is executed. In addition, patients receive parametrial boost once daily for
3 to 5 days during intracavitary brachytherapy. Concurrently, patients receive IV cisplatin
once a week for 5 weeks beginning on day 1 of external radiation therapy and once during the
parametrial boost. Patients in arm II receive external radiation therapy and brachytherapy
as previously described. [Arm II closed 8/18/98] In arm III, patients undergo external
radiation therapy as described in arm I. In addition, patients receive prolonged venous
infusion (PVI) fluorouracil daily for 5 days during external beam radiation therapy (whole
pelvis and parametrial boost). If all 6 courses of cisplatin or fluorouracil cannot be
administered during external radiation therapy, then the sixth course of chemotherapy will
be given during brachytherapy. Patients are followed every 3 months for the first 2 years,
then every 6 months for the next 3 years, then annually until death.

PROJECTED ACCRUAL: This study will accrue a maximum of 870 patients over 66 months.