Trial Information

A Randomized Phase III Study of Chemotherapy and Radiotherapy Versus Radiotherapy Alone as Adjuvant Treatment to Patients With Node Positive Stages IB or IIA Cervix Cancer

OBJECTIVES: I. Compare relapse free and overall survival after radiation therapy with or
without the sequential use of chemotherapy in patients with node positive stage IB or IIA
cervical cancer. II. Compare the toxic effects of these two treatments in this patient
population. III. Study the effect of the addition of chemotherapy on the pattern of relapse
in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
institution, stage, site of lymph node involvement, parametrial invasion, resection margin
status, diameter of the primary lesion, and preoperative brachtherapy. Patients are assigned
to one of two treatment arms and begin therapy within 6 weeks of surgery. Arm I: Patients
receive radiation therapy to the pelvis with or without brachytherapy and/or para-aortic
irradiation for 4-5 weeks. Arm II: Patients receive radiation therapy as in arm I plus 1 of
5 different cisplatin-based combination chemotherapy regimens. The patients preferably
receive chemotherapy before radiation therapy, unless doubtful or positive margins are
present, then radiation therapy is given first. Regimen I: Cisplatin and fluorouracil are
administered on days 1 and 2 of a 21 day cycle. Patients receive 4 cycles of therapy.
Regimen II: Bleomycin is administered on day 1 and cisplatin and ifosfamide are administered
on day 2 of a 21 day cycle. Patients receive 4 cycles of therapy. The regimen may also be
given without bleomycin. Regimen III: Patients receive vindesine on days 1 and 8, cisplatin
on day 1, bleomycin on days 2-4, and mitomycin on day 5 (cycles 1 and 3 only). Each cycle
lasts 21 days and patients receive 4 cycles of therapy. Regimen IV: Cisplatin and
vinblastine are administered on day 1 and bleomycin is administered on days 1, 8, and 15 of
a 21 day cycle. Each patient receives 4 cycles of therapy. Regimen V: Patients receive
cisplatin and methotrexate on day 1 of each 14 day cycle. Patients receive 6 cycles of
therapy. Patients are followed every 3 months for the first 2 years, every 6 months for the
next 3 years, then annually for the next 5 years.

PROJECTED ACCRUAL: Approximately 700 patients will be accrued for this study within 4 years.