title: Pazopanib plus weekly paclitaxel versus weekly paclitaxel alone for platinum-resistant or platinum-refractory advanced ovarian cancer (MITO 11): a randomised, open-label, phase 2 trial.
abstract: BACKGROUND
  Inhibition of angiogenesis is a valuable treatment strategy for ovarian cancer. Pazopanib is an anti-angiogenic drug active in ovarian cancer. We assessed the effect of adding pazopanib to paclitaxel for patients with platinum-resistant or platinum-refractory advanced ovarian cancer.
  
  
  METHODS
  We did this open-label, randomised phase 2 trial at 11 hospitals in Italy. We included patients with platinum-resistant or platinum-refractory ovarian cancer previously treated with a maximum of two lines of chemotherapy, Eastern Cooperative Oncology Group performance status 0-1, and no residual peripheral neurotoxicity. Patients were randomly assigned (1:1) to receive weekly paclitaxel 80 mg/m(2) with or without pazopanib 800 mg daily, and stratified by centre, number of previous lines of chemotherapy, and platinum-free interval status. The primary endpoint was progression-free survival, assessed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01644825. This report is the final analysis; the trial is completed.
  
  
  RESULTS
  Between Dec 15, 2010, and Feb 8, 2013, we enrolled 74 patients: 37 were randomly assigned to receive paclitaxel and pazopanib and 37 were randomly assigned to receive paclitaxel only. One patient, in the paclitaxel only group, withdrew from the study and was excluded from analyses. Median follow-up was 16·1 months (IQR 12·5-20·8). Progression-free survival was significantly longer in the pazopanib plus paclitaxel group than in the paclitaxel only group (median 6·35 months [95% CI 5·36-11·02] vs 3·49 months [2·01-5·66]; hazard ratio 0·42 [95% CI 0·25-0·69]; p=0·0002). We recorded no unexpected toxic effects or deaths from toxic effects. Adverse events were more common in the pazopanib and paclitaxel group than in the paclitaxel only group. The most common grade 3-4 adverse events were neutropenia (11 [30%] in the pazopanib group vs one [3%] in the paclitaxel group), fatigue (four [11%] vs two [6%]), leucopenia (four [11%] vs one [3%]), hypertension (three [8%] vs none [0%]), raised aspartate aminotransferase or alanine aminotransferase (three [8%] vs none), and anaemia (two [5%] vs five [14%]). One patient in the pazopanib group had ileal perforation.
  
  
  CONCLUSIONS
  Our findings suggest that a phase 3 study of the combination of weekly paclitaxel plus pazopanib for patients with platinum-resistant or platinum-refractory advanced ovarian cancer is warranted.
  
  
  BACKGROUND
  National Cancer Institute of Napoli and GlaxoSmithKline.
authors.affiliation: Dipartimento di Oncologia Uroginecologica, Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione GPascale IRCCS, Naples, Italy. Electronic address: s.pignata@istitutotumori.na.it.
authors.forename: Sandro
authors.initials: S
authors.lastname: Pignata
authors.affiliation: Unità di Ginecologia Oncologica, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Lorusso
authors.affiliation: Dipartimento per la Tutela della Salute della Donna della Vita Nascente del Bambino e dell' Adolescente, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.affiliation: Unità di Oncologia Medica, AORN Garibaldi - Nesima, Catania, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Sambataro
authors.affiliation: UO di Oncologia Medica, Presidio Ospedaliero di Faenza, Faenza, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Tamberi
authors.affiliation: Oncologia Medica & Breast Unit, Ospedale Antonio Perrino, Brindisi, Italy; Istituto Europeo di Oncologia, Milan, Italy.
authors.forename: Saverio
authors.initials: S
authors.lastname: Cinieri
authors.affiliation: Oncologia Medica, Ospedale S Maria della Misericordia, Perugia, Italy.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Mosconi
authors.affiliation: U O C Oncoematologia, Dipartimento di Medicina Sperimentale e Clinica F Magrassi, Seconda Università degli Studi di Napoli, Naples, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Orditura
authors.affiliation: Dipartimento di Oncologia Medica, Ospedale Bellaria-Maggiore Hospital, Azienda USL-IRCCS Istituto delle Scienze Neurologiche, Bologna, Italy.
authors.forename: Alba A
authors.initials: AA
authors.lastname: Brandes
authors.affiliation: U O Oncologia, Ospedale Infermi, Rimini, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Arcangeli
authors.affiliation: Ginecologia Oncologica, Policlinico Umberto I, Università La Sapienza, Rome, Italy.
authors.forename: Pierluigi Beneditti
authors.initials: PB
authors.lastname: Panici
authors.affiliation: Dipartimento di Oncologia Uroginecologica, Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione GPascale IRCCS, Naples, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Pisano
authors.affiliation: Dipartimento di Oncologia Uroginecologica, Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione GPascale IRCCS, Naples, Italy.
authors.forename: Sabrina C
authors.initials: SC
authors.lastname: Cecere
authors.affiliation: Dipartimento di Oncologia Uroginecologica, Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione GPascale IRCCS, Naples, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Di Napoli
authors.affiliation: Unità di Ginecologia Oncologica, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Raspagliesi
authors.affiliation: Unità di Ginecologia Oncologica, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Maltese
authors.affiliation: Dipartimento per la Tutela della Salute della Donna della Vita Nascente del Bambino e dell' Adolescente, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Vanda
authors.initials: V
authors.lastname: Salutari
authors.affiliation: Dipartimento per la Tutela della Salute della Donna della Vita Nascente del Bambino e dell' Adolescente, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Ricci
authors.affiliation: Unità Sperimentazioni Cliniche Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione GPascale IRCCS-Italia, Naples, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Daniele
authors.affiliation: Unità Sperimentazioni Cliniche Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione GPascale IRCCS-Italia, Naples, Italy.
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Piccirillo
authors.affiliation: Unità Sperimentazioni Cliniche Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione GPascale IRCCS-Italia, Naples, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Maio
authors.affiliation: Cattedra di Statistica Medica, Seconda Università degli Studi, Naples, Italy.
authors.forename: Ciro
authors.initials: C
authors.lastname: Gallo
authors.affiliation: Unità Sperimentazioni Cliniche Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione GPascale IRCCS-Italia, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Perrone
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D007191:Indazoles; D007558:Italy; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D010984:Platinum / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; D010984:Platinum; C516667:pazopanib; D017239:Paclitaxel