FOLFOX-4 3months Versus 6 Months and Bevacizumab as Adjuvant Therapy for Patients With Stage II/III Colon Cancer

NCT ID: NCT00646607

Last Updated: 2014-11-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

3756 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-06-30

Study Completion Date

2014-11-30

Brief Summary

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This project consists of two independent, following specific eligibility criteria and different randomisation schemes studies, later on called DURATION study and BEV study. Once randomised in the duration study, patients fulfilling eligibility criteria for BEV study may also be randomized to receive BEV or no BEV, in addition to FOLFOX-4 chemotherapy.

As both are open label studies, there will be no blinding of treatment assignment.

Detailed Description

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At the present time the standard treatment for resected colon cancer with high possibility of relapse ("high risk" stage II and all stage III) is represented by the regimen FOLFOX (leucovorin, bolus and infusional 5fluorouracil and oxaliplatin), which is able to increase significantly the disease-free survival (DFS) at 3 and 4 years, whereas the advantage for 5-year overall survival (OS) (which is predicted by the previous parameter) could be observed only with a further increase of follow-up. The conventional duration of chemotherapy is today of 6 months (12 courses every 2 weeks), but this long drug exposure increases the risk of long-term neurotoxicity. A reduction of adjuvant chemotherapy under 6 months was proven effective in other cancers (breast, testis…) and is better tolerated by patients in clinical practice. On the other hand, bevacizumab significantly increases OS and all other parameters when combined with standard chemotherapy in advanced disease.

Conditions

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Colon Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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A

FOLFOX-4 (infusional 5-Fluouracil, leucovorin and oxaliplatin) for 3 months or XELOX (capecitabine and oxaliplatin) for 12 weeks.

Group Type EXPERIMENTAL

FOLFOX (Oxaliplatin, 5Fluorouracil, Lederfolin)

Intervention Type DRUG

To assess whether a 3-month FOLFOX-4 treatment is at least equivalent to a 6-month FOLFOX-4 treatment

B

FOLFOX-4 (infusional 5-Fluouracil, leucovorin and oxaliplatin) for 6 months or XELOX (capecitabine and oxaliplatin) for 24 weeks.

Group Type ACTIVE_COMPARATOR

FOLFOX (Oxaliplatin, 5Fluorouracil, Lederfolin)

Intervention Type DRUG

standard treatment

Interventions

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FOLFOX (Oxaliplatin, 5Fluorouracil, Lederfolin)

To assess whether a 3-month FOLFOX-4 treatment is at least equivalent to a 6-month FOLFOX-4 treatment

Intervention Type DRUG

FOLFOX (Oxaliplatin, 5Fluorouracil, Lederfolin)

standard treatment

Intervention Type DRUG

Other Intervention Names

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FOLFOX 3 vs 6 FOLFOX 3 vs 6

Eligibility Criteria

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Inclusion Criteria

* Histologically confirmed AJCC/UICC high-risk stage II or stage III colon cancer . High-risk stage III patients (T4, N+, M0, or any T, N2, M0) may also be further randomized in the BEV study (plus or minus BEV)
* Stage II patients have to be considered at high-risk if they fulfill \>1 of the following criteria:

* T4 tumours,
* grade \>3,
* clinical presentation with bowel obstruction or perforation,
* histological signs of vascular or lymphatic or perineural invasion,
* \<12 nodes examined
* Age 18 to 75 years
* Curative surgery no less than 3 ( 4 in the BEV study) and no more than 8 weeks prior to randomization
* ECOG performance Status (ECOG-PS) \<1
* Signed written informed consent obtained prior to any study specific procedures

Exclusion Criteria

* Macroscopic or microscopic evidence of residual tumor (R1 or R2 resections).
* Previous anti-angiogenic treatment for any malignancy; cytotoxic chemotherapy, radiotherapy or immunotherapy for colon cancer
* Other malignancies within the last 5 years (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix)
* Lactating women
* Fertile women (\<2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception
* History of clinically relevant psychiatric disability , precluding informed consent
* Clinically relevant cardiovascular disease
* History or presence of other diseases
* Evidence of bleeding diathesis or coagulopathy
* Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic purposes
* Chronic, daily treatment with high-dose aspirin (\>325 mg/day) or clopidogrel (\>75 mg/day)
* Current or recent (within the 28 days prior to randomization) treatment with another investigational drug or participation in another investigational study
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mario Negri Institute for Pharmacological Research

OTHER

Sponsor Role collaborator

Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Roberto Labianca, MD

Role: PRINCIPAL_INVESTIGATOR

Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente

Alberto Sobrero, MD

Role: STUDY_CHAIR

Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente

Locations

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Ospedale Santo Spirito

Casale Monferrato, AL, Italy

Site Status

A.O. Umberto I -Università Località Torrette

Ancona, AN, Italy

Site Status

Ospedale Profili

Fabriano, AN, Italy

Site Status

Ospedale Mazzoni

Ascoli Piceno, AP, Italy

Site Status

Usl 11 Ospedale Murri

Fermo, AP, Italy

Site Status

Università di L'Aquila

L’Aquila, AQ, Italy

Site Status

ASL 8 di Arezzo

Arezzo, AR, Italy

Site Status

P.O. Ospedale S.M. Della Gruccia

Montevarchi, AR, Italy

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Ospedale Civile

Asti, AT, Italy

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Ospedale di Altamura

Altamura, BA, Italy

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Ospedali Riuniti, Largo Barozzi, 1

Bergamo, Bergamo, Italy

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A.O. Treviglio-Caravaggio, P.le Ospedale n1

Treviglio, Bergamo, Italy

Site Status

Ospedale degli Infermi

Biella, BI, Italy

Site Status

A.O. G.Rummo

Benevento, BN, Italy

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Fondazione Poliambulanza

Brescia, BS, Italy

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Ospedale S.Orsola Fatebenefratelli

Brescia, BS, Italy

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Spedali Civili

Brescia, BS, Italy

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Azienda M.Mellini-Chiara

Iseo, BS, Italy

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Ospedale di Manerbio

Manerbio, Bs, Italy

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Ospedale Regionale

Bolzano, BZ, Italy

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Ospedale S.Barbara - Asl 7

Iglesias, CA, Italy

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Policlinico Universitario

Monserrato, CA, Italy

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A.O. S.Sebastiano

Caserta, CE, Italy

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AUSL di Lanciano-Vasto

Lanciano, CH, Italy

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Ospedale S.Lazzaro

Alba, CN, Italy

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A.O. S.Croce e Carle

Cuneo, CN, Italy

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Ospedale S.Anna

Como, CO, Italy

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ospedale Valduce

Como, CO, Italy

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Ospedale Fatebenefratelli Sacra Famiglia

Erba, CO, Italy

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Azienda Istituti Ospitalieri

Cremona, CR, Italy

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Azienda Ospedaliera

Catania, CT, Italy

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ASL 6 - Ospedale Civile

Lamezia Terme, CZ, Italy

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A.O. Careggi-Università, Viale Pieraccini, 17

Florence, Firenze, Italy

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ASL 11

Empoli, FI, Italy

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Ospedale S.M.Annunziata-ASL FI

Florence, FI, Italy

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A.O. Ospedale Careggi - Università

Florence, FI, Italy

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Ospedale M.Bufalini

Cesena, FO, Italy

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A.O. Morgagni-Pierantoni

Forlì, FO, Italy

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A.O. Ospedale S.Martino

Genova, GE, Italy

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Istituto Nazionale ricerca Cancro

Genova, GE, Italy

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Università-Ospedale san Martino

Genova, GE, Italy

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Azienda Ospedaliera di Lecco

Lecco, LC, Italy

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Azienda Usl-6 Università

Livorno, LI, Italy

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Ospedale di Casalpusterlengo

Casalpusterlengo, LO, Italy

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Centro Oncologico Conti

Gaeta, Lt, Italy

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Azienda USL LT3

Latina, LT, Italy

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Ospedale Unico Versilia

Lido di Camaiore, LU, Italy

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A.O. Università-Policlinico

Messina, ME, Italy

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Ospedale Serbelloni

Gorgonzola, MI, Italy

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Azienda Ospedaliera

Legnano, MI, Italy

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Azienda Ospedale Civile

Magenta, MI, Italy

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A.O. Ospedale Fatebenefratelli

Milan, MI, Italy

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A.O. san Paolo

Milan, MI, Italy

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Casa di Cura Igea

Milan, MI, Italy

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Istituto dei Tumori

Milan, MI, Italy

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Istituto di Ricerca S.Raffaele

Milan, MI, Italy

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Istituto Europeo di Oncologia

Milan, MI, Italy

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Ospedale Luigi Sacco

Milan, MI, Italy

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Ospedale S.Carlo Borromeo

Milan, MI, Italy

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A.O. s.Gerardo

Monza, MI, Italy

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Istituto Clinico Humanitas

Rozzano, MI, Italy

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Multimedica

Sesto San Giovanni, MI, Italy

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A.O. Ospedale carlo Poma

Mantova, MN, Italy

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Ospedale ramazzini

Carpi, MO, Italy

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USL 1 di Massa e Carrara

Carrara, MS, Italy

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Ospedale Oncologico M.Ascoli

Palermo, PA, Italy

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Policlinico Giaccone

Palermo, PA, Italy

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Azienda Ospedale Civile

Piacenza, PC, Italy

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Istituto Oncologico Veneto

Padua, PD, Italy

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Ospedale Santo Spirito

Penne, PE, Italy

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Ospedale Santo Spirito

Pescara, PE, Italy

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ASL 1

Città di Castello, PG, Italy

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Centro Riferimento

Aviano, PN, Italy

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A.O. S.Maria degli Angeli

Pordenone, PN, Italy

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Ospedale ASL 4

Prato, PO, Italy

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Azienda Ospedaliera

Parma, PR, Italy

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Ospedale Santa Croce

Fano, PS, Italy

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A.O. S.Salvatore

Pesaro, PS, Italy

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Azienda Ospedaliera San Carlo

Potenza, PZ, Italy

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Centro Riferimento Oncologico Basilicata

Rionero in Volture, PZ, Italy

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Ospedale per gli Infermi

Faenza, RA, Italy

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Ospedale Umberto I

Lugo, RA, Italy

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A.O. Santa Maria delle Croci

Ravenna, RA, Italy

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Azienda Ospedali Riuniti

Reggio Calabria, RC, Italy

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A.O. Santa maria Nuova-Spallanzani

Reggio Emilia, RE, Italy

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Ospedale S.Camillo

Roma, RM, Italy

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Policlinico Militare Celio

Roma, RM, Italy

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Università Policlinico Umberto I

Roma, RM, Italy

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Ospedale Sant'Andrea

Roma, RM, Italy

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Azienda ospedaliera

Cattolica, RN, Italy

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Ospedale degli Infermi

Rimini, RN, Italy

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Università Campus Biomedico, Via Emilio Longoni, 83

Roma, Roma, Italy

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A.O. S.Giovanni Calabita Fatebenefratelli

Roma, Roma, Italy

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AULSS 18 di Rovigo

Rovigo, RO, Italy

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Ospedale Morelli

Sondalo, SO, Italy

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A.O. Valtellina e Chiavenna

Sondrio, SO, Italy

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A.O. Santa Corona

Pietra Ligure, SV, Italy

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Università degli Studi

Candiolo, TO, Italy

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Ospedale S.Giovanni Bosco

Torino, TO, Italy

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Ospedale Civile

Latisana, UD, Italy

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Casa di Cura Santa Maria

Castellanza, VA, Italy

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Ulss 5 Ovest Vicentino

Montecchio Maggiore, VI, Italy

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Ospedale Negrar

Negrar, VR, Italy

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Ospedale S.Leonardo

Castellamare Di Stabbia, , Italy

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Fondazione Pascale - Istituto Tumori

Napoli, , Italy

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Istituto Tumori- Pascale

Napoli, , Italy

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Università federico II

Napoli, , Italy

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A.O. Cardarelli

Napoli, , Italy

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Azienda Ospedaliera

Napoli, , Italy

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Ospedale S.Gennaro

Napoli, , Italy

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A.O. Ospedale Maggiore della carità

Novara, , Italy

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Countries

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Italy

References

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Gallois C, Shi Q, Meyers JP, Iveson T, Alberts SR, de Gramont A, Sobrero AF, Haller DG, Oki E, Shields AF, Goldberg RM, Kerr R, Lonardi S, Yothers G, Kelly C, Boukovinas I, Labianca R, Sinicrope FA, Souglakos I, Yoshino T, Meyerhardt JA, Andre T, Papamichael D, Taieb J. Prognostic Impact of Early Treatment and Oxaliplatin Discontinuation in Patients With Stage III Colon Cancer: An ACCENT/IDEA Pooled Analysis of 11 Adjuvant Trials. J Clin Oncol. 2023 Feb 1;41(4):803-815. doi: 10.1200/JCO.21.02726. Epub 2022 Oct 28.

Reference Type DERIVED
PMID: 36306483 (View on PubMed)

Iveson TJ, Sobrero AF, Yoshino T, Souglakos I, Ou FS, Meyers JP, Shi Q, Grothey A, Saunders MP, Labianca R, Yamanaka T, Boukovinas I, Hollander NH, Galli F, Yamazaki K, Georgoulias V, Kerr R, Oki E, Lonardi S, Harkin A, Rosati G, Paul J. Duration of Adjuvant Doublet Chemotherapy (3 or 6 months) in Patients With High-Risk Stage II Colorectal Cancer. J Clin Oncol. 2021 Feb 20;39(6):631-641. doi: 10.1200/JCO.20.01330. Epub 2021 Jan 13.

Reference Type DERIVED
PMID: 33439695 (View on PubMed)

Sobrero A, Lonardi S, Rosati G, Di Bartolomeo M, Ronzoni M, Pella N, Scartozzi M, Banzi M, Zampino MG, Pasini F, Marchetti P, Cantore M, Zaniboni A, Rimassa L, Ciuffreda L, Ferrari D, Zagonel V, Maiello E, Barni S, Rulli E, Labianca R; TOSCA Investigators. FOLFOX or CAPOX in Stage II to III Colon Cancer: Efficacy Results of the Italian Three or Six Colon Adjuvant Trial. J Clin Oncol. 2018 May 20;36(15):1478-1485. doi: 10.1200/JCO.2017.76.2187. Epub 2018 Apr 5.

Reference Type DERIVED
PMID: 29620994 (View on PubMed)

Lonardi S, Sobrero A, Rosati G, Di Bartolomeo M, Ronzoni M, Aprile G, Massida B, Scartozzi M, Banzi M, Zampino MG, Pasini F, Marchetti P, Cantore M, Zaniboni A, Rimassa L, Ciuffreda L, Ferrari D, Barni S, Zagonel V, Maiello E, Rulli E, Labianca R; TOSCA (Three or Six Colon Adjuvant) Investigators. Phase III trial comparing 3-6 months of adjuvant FOLFOX4/XELOX in stage II-III colon cancer: safety and compliance in the TOSCA trial. Ann Oncol. 2016 Nov;27(11):2074-2081. doi: 10.1093/annonc/mdw404. Epub 2016 Aug 29.

Reference Type DERIVED
PMID: 27573560 (View on PubMed)

Other Identifiers

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2007-000354-31

Identifier Type: -

Identifier Source: org_study_id