title: Phase III trial comparing 3-6 months of adjuvant FOLFOX4/XELOX in stage II-III colon cancer: safety and compliance in the TOSCA trial.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  NCT00646607.
authors: Medical Oncology Unit 1, Istituto Oncologico Veneto-IRCCS, Padova.
authors: S
authors: S
authors: Lonardi
authors: Medical Oncology Unit, IRCCS San Martino-IST, Genova.
authors: A
authors: A
authors: Sobrero
authors: Medical Oncology Unit, Ospedale San Carlo, Potenza.
authors: G
authors: G
authors: Rosati
authors: Medical Oncology Unit, Fondazione Istituto Nazionale Tumori-IRCCS, Milano.
authors: M
authors: M
authors: Di Bartolomeo
authors: Medical Oncology Unit, Ospedale San Raffaele-IRCCS, Milano.
authors: M
authors: M
authors: Ronzoni
authors: Medical Oncology Unit, Azienda Ospedaliero Universitaria Santa Maria della Misericordia, Udine.
authors: G
authors: G
authors: Aprile
authors: B
authors: B
authors: Massida
authors: Medical Oncology, University Hospital and University of Cagliari, Cagliari.
authors: M
authors: M
authors: Scartozzi
authors: Medical Oncology Unit, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia.
authors: M
authors: M
authors: Banzi
authors: Gastrointestinal Medical Oncology Unit and Neuroendocrine Tumors, Istituto Europeo di Oncologia-IRCCS, Milano.
authors: M G
authors: MG
authors: Zampino
authors: Medical Oncology Unit, Ospedale Santa Maria della Misericordia, Rovigo.
authors: F
authors: F
authors: Pasini
authors: Medical Oncology Unit, Sant'Andrea Hospital, Sapienza University of Rome and IDI-IRCCS, Roma.
authors: P
authors: P
authors: Marchetti
authors: Medical Oncology Unit, Civico Hospital Carrara (MS).
authors: M
authors: M
authors: Cantore
authors: Medical Oncology Unit, Fondazione Poliambulanza, Brescia.
authors: A
authors: A
authors: Zaniboni
authors: Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano (MI).
authors: L
authors: L
authors: Rimassa
authors: Medical Oncology Unit, Azienda Ospedaliero Universitaria San Giovanni Battista, Molinette, Torino.
authors: L
authors: L
authors: Ciuffreda
authors: Medical Oncology Unit, Azienda Ospedaliera San Paolo, Milano.
authors: D
authors: D
authors: Ferrari
authors: Medical Oncology, ASST Bergamo Ovest, Ospedale di Treviglio, Bergamo.
authors: S
authors: S
authors: Barni
authors: Medical Oncology Unit 1, Istituto Oncologico Veneto-IRCCS, Padova.
authors: V
authors: V
authors: Zagonel
authors: Medical Oncology Unit, Ospedale Casa Sollievo della Sofferenza-IRCCS, San Giovanni Rotondo.
authors: E
authors: E
authors: Maiello
authors: Laboratory of Clinical Research Methodology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milano.
authors: E
authors: E
authors: Rulli
authors: Medical Oncology Unit, ASST Papa Giovanni XXIII, Bergamo, Italy rlabian@tin.it.
authors: R
authors: R
authors: Labianca
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab / Q000008:administration & dosage; D000069287:Capecitabine; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D010071:Oxaloacetates; D010349:Patient Compliance
chemical_list: D009944:Organoplatinum Compounds; D010071:Oxaloacetates; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D002955:Leucovorin; D005472:Fluorouracil
keywords: adjuvant chemotherapy; colon cancer; duration