WEEKLY CHEMOTHERAPY FOR OVARIAN CANCER

Lancet Oncol. 2014 Feb 27. pii: S1470-2045(14)70049-X. doi: 10.1016/S1470-2045(14)70049-X. [Epub ahead of print]

Carboplatin plus paclitaxel once a week versus every 3 weeks in patients with advanced ovarian cancer (MITO-7): a randomised, multicentre, open-label, phase 3 trial.

Pignata S1, Scambia G2, Katsaros D3, Gallo C4, Pujade-Lauraine E5, De Placido S6, Bologna A7, Weber B8, Raspagliesi F9, Panici PB10, Cormio G11, Sorio R12,Cavazzini MG13, Ferrandina G14, Breda E15, Murgia V16, Sacco C17, Cinieri S18, Salutari V2, Ricci C2, Pisano C19, Greggi S19, Lauria R6, Lorusso D9, Marchetti C10, Selvaggi L11, Signoriello S4, Piccirillo MC20, Di Maio M20, Perrone F20; on behalf of the Multicentre Italian Trials in Ovarian cancer (MITO-7); Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens et du sein (GINECO); Mario Negri Gynecologic Oncology (MaNGO); European Network of Gynaecological Oncological Trial Groups (ENGOT-OV-10); Gynecologic Cancer InterGroup (GCIG) Investigators.

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Abstract

BACKGROUND:

Carboplatin plus paclitaxel administered every 3 weeks is standard first-line chemotherapy for patients with advanced ovarian cancer. A weekly paclitaxel schedule combined with carboplatin every 3 weeks prolonged progression-free survival and overall survival in a Japanese phase 3 trial. The aim of our study was to assess whether a weekly schedule of carboplatin plus paclitaxel is more effective than the same drugs given every 3 weeks.

METHODS:

We did a multicentre, randomised, phase 3 study at 67 institutions in Italy and France. Women with FIGO stage IC-IV ovarian cancer, an ECOG performance status of 2 or lower, and who had never received chemotherapy were randomly allocated in a 1:1 ratio to receive either carboplatin (AUC 6 mg/mL per min) plus paclitaxel (175 mg/m2) every 3 weeks for six cycles or carboplatin (AUC 2 mg/mL per min) plus paclitaxel (60 mg/m2) every week for 18 weeks. Randomisation was done by computer-based minimisation, stratified by centre, residual disease after surgery, and ECOG performance status. The study was not blinded. Coprimary endpoints were progression-free survival and quality of life (assessed by the Functional Assessment of Cancer Therapy Ovarian Trial Outcome Index [FACT-O/TOI] score), and analysis was by modified intention to treat. This report presents the final analysis. The study is registered with ClinicalTrials.gov, number NCT00660842.

FINDINGS:

822 patients were enrolled into the study between Nov 20, 2008, and March 1, 2012; 12 withdrew their consent immediately after randomisation and were excluded, and 810 were eligible for analysis. 404 women were allocated treatment every 3 weeks and 406 were assigned to the weekly schedule. After median follow-up of 22·3 months (IQR 16·2-30·9), 449 progression-free survival events were recorded. Median progression-free survival was 17·3 months (95% CI 15·2-20·2) in patients assigned to treatment every 3 weeks, versus 18·3 months (16·8-20·9) in women allocated to the weekly schedule (hazard ratio 0·96, 95% CI 0·80-1·16; p=0·66). FACT-O/TOI scores differed significantly between the two schedules (treatment-by-time interaction p<0 11="" 1="" 200="" 27="" 2="" 3-4="" 399="" 3="" 400="" 4="" 68="" 7="" after="" allocated="" and="" assigned="" at="" attributed="" chemotherapy="" cycle="" death="" deaths="" died="" during="" every="" fact-o="" febrile="" fewer="" for="" four="" grade="" group="" had="" in="" neuropathy="" neutropenia="" of="" one="" or="" p="" patients="" recorded="" regimen.="" remained="" schedule="" scores="" stable.="" study="" than="" the="" those="" three="" thrombocytopenia="" to="" transient="" treatment="" two="" vs="" was="" week="" weekly="" weeks="" were="" whereas="" who="" with="" women="" worse="" worsened="" worsening="">

INTERPRETATION:

A weekly regimen of carboplatin and paclitaxel might be a reasonable option for first-line treatment of women with advanced ovarian cancer.