Randomized Phase III Study Of Neoadjuvant Chemotherapy Followed By Surgery Vs. Concomitant Radiotherapy And Chemotherapy In FIGO Ib2, IIa>4 cm or IIb Cervical Cancer
- Compare the overall and progression-free survival of patients with stage IB2, IIA, or
IIB cervical cancer treated with neoadjuvant cisplatin-based chemotherapy followed by
radical hysterectomy vs standard therapy comprising concurrent radiotherapy and
- Compare the toxicity of these regimens in these patients.
- Compare the quality of life of patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
participating center, FIGO stage, age (18 to 50 vs 51 to 75), and histological subtype
(adenomatous vs non-adenomatous component). Patients are randomized to 1 of 2 treatment
- Arm I: Patients receive neoadjuvant cisplatin-based chemotherapy on day 1. Treatment
repeats every 21 days. Within 6 weeks after the last chemotherapy course, patients
undergo a type III-V Piver-Rutledge radical hysterectomy. Patients with positive lymph
nodes or tumor invasion into the parametria or less than 5 mm from the resection
borders after surgery receive standard adjuvant external beam radiotherapy once daily,
5 days a week, for 5-5.6 weeks (25-28 treatment days) followed by external boost
radiotherapy or brachytherapy for 1 or 2 days.
- Arm II: Patients receive standard therapy comprising radiotherapy as in arm I
concurrently with cisplatin-based chemotherapy once weekly for 6 weeks. Adjuvant
hysterectomy is allowed, but not recommended, in case of histologically proven residual
Treatment in both arms continues in the absence of disease progression or unacceptable
toxicity. For patients in both arms, cisplatin may be combined with other chemotherapeutics
as long as the minimum platinum dose is given.
Quality of life is assessed at baseline and at 6, 12, 18, and 24 months.
Patients are followed every 3 months for 1 year, every 6 months for 4 years, and then
PROJECTED ACCRUAL: A total of 686 patients (343 per treatment arm) will be accrued for this
study within 3.8 years.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall survival as measured by Kaplan Meier after each course, every 3 months for 1 year, every 6 months for 4 years, and then annually
16 years from FPI
Fabio Landoni, MD
Istituto Europeo Di Oncologia, Milano
Austria: Agency for Health and Food Safety