Phase III trial comparing 3-6 months of adjuvant FOLFOX4/XELOX in stage II-III colon cancer: safety and compliance in the TOSCA trial
S Lonardi, A Sobrero, G Rosati, M Di Bartolomeo, M Ronzoni, G Aprile, B Massida, M Scartozzi, M Banzi, M G Zampino, F Pasini, P Marchetti, M Cantore, A Zaniboni, L Rimassa, L Ciuffreda, D Ferrari, S Barni, V Zagonel, E Maiello, E Rulli, R Labianca, TOSCA (Three or Six Colon Adjuvant) Investigators, D Bilancia, G Rosati, V Montesarchio, R V Iaffaioli, G Nasti, B Daniele, V Zagonel, S Lonardi, N Pella, G Aprile, F Pasini, P Marchetti, A Romiti, L Ciuffreda, D Ferrari, P Foa, A Zaniboni, R Labianca, S Mosconi, A Sobrero, P Bidoli, M Cazzaniga, G D Beretta, D C Corsi, E Cortesi, S Barni, F Petrelli, M Cantore, E Maiello, S Cinieri, M Banzi, A Santoro, F Artioli, R Mattioli, D Amoroso, D Amadori, L Frassineti, D Turci, A Ravaioli, E Bajetta, M Di Bartolomeo, L Gianni, M Ronzoni, M T Ionta, B Massidda, M Scartozzi, M G Zampino, A Bochicchio, A Ciarlo, A Di Leo, S De Placido, C Carlomagno, V Adamo, D Natale, E Rulli, F Galli, D Poli, V Torri, S Lonardi, A Sobrero, G Rosati, M Di Bartolomeo, M Ronzoni, G Aprile, B Massida, M Scartozzi, M Banzi, M G Zampino, F Pasini, P Marchetti, M Cantore, A Zaniboni, L Rimassa, L Ciuffreda, D Ferrari, S Barni, V Zagonel, E Maiello, E Rulli, R Labianca, TOSCA (Three or Six Colon Adjuvant) Investigators, D Bilancia, G Rosati, V Montesarchio, R V Iaffaioli, G Nasti, B Daniele, V Zagonel, S Lonardi, N Pella, G Aprile, F Pasini, P Marchetti, A Romiti, L Ciuffreda, D Ferrari, P Foa, A Zaniboni, R Labianca, S Mosconi, A Sobrero, P Bidoli, M Cazzaniga, G D Beretta, D C Corsi, E Cortesi, S Barni, F Petrelli, M Cantore, E Maiello, S Cinieri, M Banzi, A Santoro, F Artioli, R Mattioli, D Amoroso, D Amadori, L Frassineti, D Turci, A Ravaioli, E Bajetta, M Di Bartolomeo, L Gianni, M Ronzoni, M T Ionta, B Massidda, M Scartozzi, M G Zampino, A Bochicchio, A Ciarlo, A Di Leo, S De Placido, C Carlomagno, V Adamo, D Natale, E Rulli, F Galli, D Poli, V Torri
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.
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Source: PubMed