SNFGE SNFGE
 
Thématique :
- Cancers autres (hors CCR et CHC)
Originalité :
Intermédiaire
Solidité :
Intermédiaire
Doit faire évoluer notre pratique :
Pas encore
 
 
Nom du veilleur :
Professeur Thomas APARICIO
Coup de coeur :
 
 
The Lancet Oncology
  2016/01  
 
  2016 Jan;17(1):99-108  
  doi: 10.1016/S1470-2045(15)00410-6. Epub 2015 Nov 28.  
 
  S-1 plus leucovorin versus S-1 plus leucovorin and oxaliplatin versus S-1 plus cisplatin in patients with advanced gastric cancer: a randomised, multicentre, open-label, phase 2 trial.  
 
  Hironaka S, Sugimoto N, Yamaguchi K, Moriwaki T, Komatsu Y, Nishina T, Tsuji A, Nakajima TE, Gotoh M, Machida N, Bando H, Esaki T, Emi Y, Sekikawa T, Matsumoto S, Takeuchi M, Boku N, Baba H, Hyodo I.  
  http://www.ncbi.nlm.nih.gov/pubmed/?term=S-1+plus+leucovorin+versus+S-1+plus+leucovorin+and+oxaliplatin+versus+S-1+plus+cisplatin+in+patients+with+advanced+gastric+cancer%3A+a+randomised%2C+multicentre%2C+open-label%2C+phase+2+trial.  
 
 

BACKGROUND: Although leucovorin enhances the efficacy of fluorouracil, the anti-tumour activity of S-1 and leucovorin and their combination with oxaliplatin for patients with advanced gastric cancer is unknown. We compared the activity and safety of S-1 plus leucovorin, S-1 plus leucovorin and oxaliplatin, and S-1 plus cisplatin as first-line chemotherapy for advanced gastric cancer.

METHODS: In this multicentre, randomised, open-label, phase 2 trial, we recruited chemotherapy-naive patients with unresectable or recurrent gastric cancer with measurable lesions aged 20 years or older from 25 general hospitals and specialist centres in Japan. Patients were randomly assigned (1:1:1) centrally to receive S-1 plus leucovorin (S-1 40-60 mg orally plus oral leucovorin 25 mg twice a day for 1 week, every 2 weeks), S-1 plus leucovorin and oxaliplatin (S-1 plus leucovorin and intravenous oxaliplatin 85 mg/m(2) on day 1, every 2 weeks), or S-1 plus cisplatin (S-1 40-60 mg orally twice a day for 3 weeks, plus intravenous cisplatin 60 mg/m(2) on day 8, every 5 weeks). Randomisation was done with the minimisation method using performance status (0 vs 1) and tumour stage (stage IV vs recurrent) as stratification factors. The primary endpoint was independently reviewed overall response in the full analysis set. This trial is registered with Japic CTI, number 111635.

FINDINGS: Between Oct 20, 2011, and Dec 17, 2012, we enrolled and randomly assigned 145 patients: 49 patients were assigned to S-1 plus leucovorin, 47 to S-1 plus leucovorin and oxaliplatin, and 49 to S-1 plus cisplatin. An objective response assessed by the independent review committee was achieved in 20 (43% [95% CI 28·3-57·8]) of the 47 patients in the S-1 plus leucovorin group, 31 (66% [50·7-79·1]) of the 47 patients in the S-1 plus leucovorin and oxaliplatin group, and 22 (46% [31·4-60·8]) of the 48 patients in the S-1 plus cisplatin group (Fisher's exact test, p=0·84 for S-1 plus leucovorin vs S-1 plus cisplatin, p=0·063 for S-1 plus leucovorin and oxaliplatin vs S-1 plus cisplatin, and p=0·038 for S-1 plus leucovorin and oxaliplatin vs S-1 plus leucovorin). The most common grade 3-4 adverse events were neutropenia (three [6%] of 48 patients in the S-1 plus leucovorin group vs 12 [26%] of 47 patients in the S-1 plus leucovorin and oxaliplatin group vs 17 [35%] of 49 patients in the S-1 plus cisplatin group), decreased appetite (six [13%] vs 14 [30%] vs 12 [24%]), anaemia (five [10%] vs seven [15%] vs 13 [27%]), and hyponatraemia (two [4%] vs two [4%] vs nine [18%]).

INTERPRETATION: S-1 plus leucovorin and oxaliplatin was more active than S-1 plus leucovorin or S-1 plus cisplatin with acceptable toxic effects for patients with advanced gastric cancer. A phase 3 trial comparing S-1 plus leucovorin and oxaliplatin with S-1 plus cisplatin is underway.

 
Question posée
 
Quelle association avec le S1 dans le traitement de l’adénocarcinome avancé ?
 
Question posée
 
L’association S1 + oxaliplatine donne un meilleur taux de réponse que l’association S1 + cisplatine ou le S1 seul.
 
Commentaires

Le S1 n’est pas disponible en France. Il s’agit d’une nouvelle étude en faveur d’une polychimiothérapie à base d’oxaliplatine plutôt que de cisplatine>.

 
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