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Lancet Oncol. 2014 Apr;15(4):396-405. doi: 10.1016/S1470-2045(14)70049-X. Epub 2014 Feb 28.

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.

Author information

1
Dipartimento di Oncologia Uroginecologica, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione G Pascale, IRCCS, Napoli, Italy. Electronic address: s.pignata@istitutotumori.na.it.
2
Dipartimento per la Tutela della Salute della Donna, della Vita Nascente, del Bambino e dell' Adolescente, Università Cattolica del Sacro Cuore, Roma, Italy.
3
Ginecologia Oncologica, Azienda Ospedaliera Città della Salute e della Scienza, Presidio S Anna e Università, Torino, Italy.
4
Statistica Medica, Seconda Università di Napoli, Napoli, Italy.
5
Hôpital Hôtel-Dieu, Paris, France.
6
Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, Napoli, Italy.
7
Oncologia Medica, Azienda Ospedaliera ASMN, IRCCS, Reggio Emilia, Italy.
8
Centre Alexis Vautrin, Vandoeuvre-Les-Nancy, France.
9
Unità di Ginecologia Oncologica, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS, Milano, Italy.
10
Dipartimento di Scienze Ginecologico-Ostetriche e Scienze Urologiche, Università La Sapienza, Roma, Italy.
11
Ginecologia ed Ostetricia, Policlinico, Bari, Italy.
12
Oncologia Medica C, Centro di Riferimento Oncologico, Aviano-PN, Italy.
13
Oncologia ed Ematologia, AO Carlo Poma, Mantova, Italy.
14
Ginecologia Oncologica, Centro di Ricerca e Formazione ad Alta Tecnologia nelle Scienze Biomediche, Università Cattolica del Sacro Cuore, Campobasso, Italy.
15
Oncologia Medica Ospedale S Giovanni Calibita Fatebenefratelli, Roma, Italy.
16
Oncologia Medica Ospedale S Chiara, Trento, Italy.
17
Dipartimento di Oncologia AO S Maria della Misericordia, Udine, Italy.
18
Oncologia Medica, Ospedale Antonio Perrino, Brindisi, and Istituto Europeo di Oncologia, Milano, Italy.
19
Dipartimento di Oncologia Uroginecologica, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione G Pascale, IRCCS, Napoli, Italy.
20
Unità Sperimentazioni Cliniche, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione G Pascale, IRCCS, Napoli, Italy.

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/m(2)) every 3 weeks for six cycles or carboplatin (AUC 2 mg/mL per min) plus paclitaxel (60 mg/m(2)) 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<0·0001); with treatment every 3 weeks, FACT-O/TOI scores worsened at every cycle (weeks 1, 4, and 7), whereas for the weekly schedule, after transient worsening at week 1, FACT-O/TOI scores remained stable. Fewer patients assigned to the weekly group than those allocated treatment every 3 weeks had grade 3-4 neutropenia (167 [42%] of 399 patients vs 200 [50%] of 400 patients), febrile neutropenia (two [0·5%] vs 11 [3%]), grade 3-4 thrombocytopenia (four [1%] vs 27 [7%]), and grade 2 or worse neuropathy (24 [6%] vs 68 [17%]). Three deaths during the study were attributed to chemotherapy; two women died who were allocated treatment every 3 weeks and one death was recorded in the group assigned the weekly regimen.

INTERPRETATION:

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

FUNDING:

None.

PMID:
24582486
DOI:
10.1016/S1470-2045(14)70049-X
[Indexed for MEDLINE]

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