504PD - Three or six months of adjuvant chemotherapy for colon cancer: Compliance and safety of the phase III Italian TOSCA trial

Date 27 September 2014
Event ESMO 2014
Session Gastrointestinal tumours, colorectal
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Presenter Sara Lonardi
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors S. Lonardi1, R. Labianca2, G. Rosati3, M. Di Bartolomeo4, L. Gianni5, N. Pella6, B. Massidda7, C. Boni8, M.G. Zampino9, F. Pasini10, P. Marchetti11, M. Cantore12, A. Santoro13, L. Ciuffreda14, D. Ferrari15, A. Zaniboni16, V. Montesarchio17, E. Maiello18, I.C. Floriani19, A. Sobrero20
  • 1Oncologia Medica 1, Istituto Oncologico Veneto IRCCS, 35128 - Padova/IT
  • 2Oncology And Haematology, Ospedali Riuniti di Bergamo, 24100 - Bergamo/IT
  • 3Oncologia Medica, Azienda Ospedaliera S.Carlo, Potenza/IT
  • 4Oncologia Medica 1, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT
  • 5Medical Oncology, IRCCS San Raffaele, 20132 - Milano/IT
  • 6Oncologia Medica, Azienda Ospedaliera Universitaria-Udine Sta Maria della Misericordia, Udine/IT
  • 7Oncologia Medica 1, Azienda Ospedaliero Universitaria Cagliari, IT-09042 - Monserrato/IT
  • 8Oncology Dept., Arcispedale S. Maria NuovaDivisione di Oncologia, IT-42100 - Reggio Emilia/IT
  • 9Oncologia Medica, Istituto Europeo di Oncologia, IT-20141 - Milano/IT
  • 10Medical Oncology, Ospedale S. Maria della Misericordia Azienda Sanitaria Local 18 Rovigo, Rovigo/IT
  • 11Oncologia Medica, Azienda Ospedaliera St. Andrea - Roma, IT-00189 - Roma/IT
  • 12Oncologia Medica, Azienda Ospedaliera USL 1, Massa Carrara/IT
  • 13Medical Oncology, Humanitas Cancer Center, IRCCS, IT-20089 - Rozzano/IT
  • 14S.c. Oncologia Medica 1, A.O. Citta' della Salute e della Scienza di Torino, Torino/IT
  • 15Madical Oncology, Polo Universitario San Paolo Hospital, 30100 - Milano/IT
  • 16Oncology Department, Fondazione Poliambulanza, IT-25124 - Brescia/IT
  • 17Uoc Oncologia, Azienda Ospedaliera Dei Colli-Monaldi, Napoli/IT
  • 18Medical Oncology, Ospedale Casa Sollievo della Sofferenza, S.Giovanni Rotondo/IT
  • 19Laboratory Of Clinical Research. Department Of Oncology, IRCCS - Istituto di Ricerche Farmacologiche “Mario Negri”, 20156 - Milan/IT
  • 20Oncologia Medica, IRCCS AOU San Martino - IST-Istituto Nazionale per la Ricerca sul Cancro, 16132 - Genova/IT

Abstract

Aim

Six months FOLFOX4 or XELOX is the standard adjuvant chemotherapy in radically resected stage III colon cancer, however a shorter duration of therapy could be equally efficacious.

Methods

This is an Italian, multicenter, non-inferiority phase III trial randomizing patients (pts) with stage III and high risk stage II colon cancer to receive 3 (arm 3) vs 6 (arm 6) months of FOLFOX4 or XELOX. Primary end-point is relapse free survival (RFS), and the arm 3 will be considered non-inferior if the superior margin of the 95% CI of the HR is <= 1.20. 1270 relapses/deaths are required to have a power of 90%.

Results

From June 2007 to March 2013, 3,759 patients were accrued and 3,738 (1860 in arm 3 and 1878 in arm 6) included in the intent-to-treat (ITT) population, since 21 pts were excluded due to major violations. The proportion of FOLFOX4 vs XELOX was 64% vs 36% in both arms. Among the ITT population, demographic factors (including gender and age) were balanced in the two arms. As expected, compliance was higher in arm 3 than in arm 6: treatment completion rate without any modification of planned dose and timing was 35% in arm 3 and 12% in arm 6, while approximately 55% pts in both arms completed treatment with modifications of dose and/or timing, resulting in 90% vs 67% pts receiving all the planned cycles. Therapy was permanently interrupted due to toxicity in 5% of pts in arm 3 and 17% in arm 6. The overall incidence of grade 3-4 toxicity (including grade 2 oxaliplatin neurotoxicity) events was 37% in arm 3 and 60% in arm 6. Grade 2+ neuropathy was more frequent in arm 6 than in arm 3: 32 % vs 9%, respectively. With a median follow-up of 30 months, 476 pts relapsed, 195 died and 520 relapsed and/or died.

Conclusions

TOSCA is the first trial completing the accrual among the international initiative of comparing 3 vs 6 months of adjuvant treatment in colon cancer (IDEA). In general, reported toxicity was low, but, as expected, significantly higher in the 6-month arm compared to that of the 3-month arm; accordingly, compliance was lower in the standard 6-month arm. Data for efficacy analysis are premature.

Disclosure

All authors have declared no conflicts of interest.