The published studies suggest that for selected women with stage IIIC or IV epithelial ovarian cancer , neoadjuvant chemotherapy and interval cytoreduction are non-inferior to primary cytoreduction and adjuvant chemotherapy with respect to overall and progression-free survival and are associated with less perioperative morbidity and mortality .
PURPOSE To provide guidance to clinicians regarding the use of neoadjuvant chemotherapy and interval cytoreduction among women with stage IIIC or IV epithelial ovarian cancer .
Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial
BACKGROUND The international st and ard of care for women with suspected advanced ovarian cancer is surgical debulking followed by platinum-based chemotherapy . We aim ed to establish whether use of platinum-based primary chemotherapy followed by delayed surgery was an effective and safe alternative treatment regimen . METHODS In this phase 3 , non-inferiority , r and omised , controlled trial ( CHORUS ) undertaken in 87 hospitals in the UK and New Zeal and , we enrolled women with suspected stage III or IV ovarian cancer . We r and omly assigned women ( 1:1 ) either to undergo primary surgery followed by six cycles of chemotherapy , or to three cycles of primary chemotherapy , then surgery , followed by three more cycles of completion chemotherapy . Each 3-week cycle consisted of carboplatin AUC5 or AUC6 plus paclitaxel 175 mg/m(2 ) , or an alternative carboplatin combination regimen , or carboplatin monotherapy . We did the r and om assignment by use of a minimisation method with a r and om element , and stratified participants according to the r and omising centre , largest radiological tumour size , clinical stage , and prespecified chemotherapy regimen . Patients and investigators were not masked to group assignment . The primary outcome measure was overall survival . Primary analyses were done in the intention-to-treat population . To establish non-inferiority , the upper bound of a one-sided 90 % CI for the hazard ratio ( HR ) had to be less than 1.18 . This trial is registered , number IS RCT N74802813 , and is closed to new participants . FINDINGS Between March 1 , 2004 , and Aug 30 , 2010 , we r and omly assigned 552 women to treatment . Of the 550 women who were eligible , 276 were assigned to primary surgery and 274 to primary chemotherapy . All were included in the intention-to-treat analysis ; 251 assigned to primary surgery and 253 to primary chemotherapy were included in the per- protocol analysis . As of May 31 , 2014 , 451 deaths had occurred : 231 in the primary -surgery group versus 220 in the primary -chemotherapy group . Median overall survival was 22.6 months in the primary -surgery group versus 24.1 months in primary chemotherapy . The HR for death was 0.87 in favour of primary chemotherapy , with the upper bound of the one-sided 90 % CI 0.98 ( 95 % CI 0.72 - 1.05 ) . Grade 3 or 4 postoperative adverse events and deaths within 28 days after surgery were more common in the primary -surgery group than in the primary -chemotherapy group ( 60 [ 24 % ] of 252 women vs 30 [ 14 % ] of 209 , p=0.0007 , and 14 women [ 6 % ] vs 1 woman [ < 1 % ] , p=0.001 ) . The most common grade 3 or 4 postoperative adverse event was haemorrhage in both groups ( 8 women [ 3 % ] in the primary -surgery group vs 14 [ 6 % ] in the primary -chemotherapy group ) . 110 ( 49 % ) of 225 women receiving primary surgery and 102 ( 40 % ) of 253 receiving primary chemotherapy had a grade 3 or 4 chemotherapy related toxic effect ( p=0.0654 ) , mostly uncomplicated neutropenia ( 20 % and 16 % , respectively ) . One fatal toxic effect , neutropenic sepsis , occurred in the primary -chemotherapy group . INTERPRETATION In women with stage III or IV ovarian cancer , survival with primary chemotherapy is non-inferior to primary surgery . In this study population , giving primary chemotherapy before surgery is an acceptable st and ard of care for women with advanced ovarian cancer . FUNDING Cancer Research UK and the Royal College of Obstetricians and Gynaecologists
The published studies suggest that for selected women with stage IIIC or IV epithelial ovarian cancer , neoadjuvant chemotherapy and interval cytoreduction are non-inferior to primary cytoreduction and adjuvant chemotherapy with respect to overall and progression-free survival and are associated with less perioperative morbidity and mortality .
PURPOSE To provide guidance to clinicians regarding the use of neoadjuvant chemotherapy and interval cytoreduction among women with stage IIIC or IV epithelial ovarian cancer .