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Ann Oncol. 2016 Nov;27(11):2074-2081. Epub 2016 Aug 29.

Phase III trial comparing 3-6 months of adjuvant FOLFOX4/XELOX in stage II-III colon cancer: safety and compliance in the TOSCA trial.

Author information

1
Medical Oncology Unit 1, Istituto Oncologico Veneto-IRCCS, Padova.
2
Medical Oncology Unit, IRCCS San Martino-IST, Genova.
3
Medical Oncology Unit, Ospedale San Carlo, Potenza.
4
Medical Oncology Unit, Fondazione Istituto Nazionale Tumori-IRCCS, Milano.
5
Medical Oncology Unit, Ospedale San Raffaele-IRCCS, Milano.
6
Medical Oncology Unit, Azienda Ospedaliero Universitaria Santa Maria della Misericordia, Udine.
7
Medical Oncology, University Hospital and University of Cagliari, Cagliari.
8
Medical Oncology Unit, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia.
9
Gastrointestinal Medical Oncology Unit and Neuroendocrine Tumors, Istituto Europeo di Oncologia-IRCCS, Milano.
10
Medical Oncology Unit, Ospedale Santa Maria della Misericordia, Rovigo.
11
Medical Oncology Unit, Sant'Andrea Hospital, Sapienza University of Rome and IDI-IRCCS, Roma.
12
Medical Oncology Unit, Civico Hospital Carrara (MS).
13
Medical Oncology Unit, Fondazione Poliambulanza, Brescia.
14
Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano (MI).
15
Medical Oncology Unit, Azienda Ospedaliero Universitaria San Giovanni Battista, Molinette, Torino.
16
Medical Oncology Unit, Azienda Ospedaliera San Paolo, Milano.
17
Medical Oncology, ASST Bergamo Ovest, Ospedale di Treviglio, Bergamo.
18
Medical Oncology Unit, Ospedale Casa Sollievo della Sofferenza-IRCCS, San Giovanni Rotondo.
19
Laboratory of Clinical Research Methodology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milano.
20
Medical Oncology Unit, ASST Papa Giovanni XXIII, Bergamo, Italy rlabian@tin.it.

Abstract

BACKGROUND:

Six months of oxaliplatin-based adjuvant chemotherapy is standard of care for radically resected stage III colon cancer and an accepted option for high-risk stage II. A shorter duration of therapy, if equally efficacious, would be advantageous for patients and Health-Care Systems.

PATIENTS AND METHODS:

TOSCA ['Randomized trial investigating the role of FOLFOX-4 or XELOX (3 versus 6 months) regimen duration and bevacizumab as adjuvant therapy for patients with stage II/III colon cancer] is an open-label, phase III, multicenter, noninferiority trial randomizing patients with high-risk stage II or stage III radically resected colon cancer to receive 3 months (arm 3 m) versus 6 months (arm 6 m) of FOLFOX4/XELOX. Primary end-point was relapse-free survival. We present here safety and compliance data.

RESULTS:

From June 2007 to March 2013, 3759 patients were accrued from 130 Italian sites, 64% receiving FOLFOX4 and 36% XELOX in either arm. Treatment completion rate without any modification was 35% versus 12% and with delays or dose reduction 52% versus 44% in arm 3 and 6 m. Treatment was permanently discontinued in 8% (arm 3 m) and 33% (arm 6 m). In arm 6 m, 50% of patients discontinuing treatment did so after completing 80% of planned program. Grade 3+ toxicities were higher in arm 6 m than that in 3 m. Grade 2+ neuropathy was 31.2% versus 8.8% (P < 0.0001) while grade 3+ was 8.4 versus 1.3 (P < 0.0001), in arm 3 and 6 m. Seven deaths within 30 days from last treatment administration in arm 6 m and three deaths in arm 3 m were observed (0.3% versus 0.1%, P = 0.34).

CONCLUSIONS:

TOSCA is the first trial comparing 3 versus 6 months of adjuvant chemotherapy completing accrual within the international initiative of treatment duration evaluation (International Duration Evaluation of Adjuvant, IDEA). High compliance to treatment in control arm will allow a correct assessment of potential differences between the two treatment durations.

CLINICALTRIALSGOV REGISTRATION NUMBER:

NCT00646607.

KEYWORDS:

adjuvant chemotherapy; colon cancer; duration

PMID:
27573560
DOI:
10.1093/annonc/mdw404
[Indexed for MEDLINE]
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