title: Is adjuvant therapy with streptozotocin and 5-fluorouracil useful after resection of liver metastases from digestive endocrine tumors?
abstract: BACKGROUND
  In patients with digestive endocrine tumors (DET) and liver metastases (LM) surgical resection is the only curative treatment. However, 5-year recurrence occurs in 50-80% of patients in the literature. The effect of adjuvant chemotherapy (CT) on relapse-free survival (RFS) and overall survival (OS) is unknown.
  
  
  OBJECTIVE
  To assess the safety and the efficacy of systemic adjuvant CT with streptozotocin and 5-fluorouracil (5-FU) following LM resection in patients with DET.
  
  
  METHODS
  Between 1996 and 2006, 52 consecutive patients (23 males, median age 54 years [21-69]) underwent surgery for LM of well-differentiated DET in our center. The primary tumor was resected. After R0 resection of LM, patients were considered for adjuvant CT if the primary tumor was pancreatic, if LM was >or=10, or if the patient was <50 years old, in patients with other primary tumors. Twenty-nine patients received adjuvant CT and 23 were in the observation group. Adjuvant CT included 4 postoperative courses of i.v. streptozotocin-5-FU (500 and 400 mg/m(2), respectively, daily for 5 days every 42 days). RFS, OS and toxicity were evaluated. Log rank and chi-square analysis were used to identify prognostic factors.
  
  
  RESULTS
  Median post-operative follow-up was 47 months (4-162). In the adjuvant CT group, all patients except one received the 4 cycles. Two patients had grade 3-4 toxicity, including 1 febrile neutropenia resulting in death. Recurrence occurred in 43% and 65% of patients in the observation and adjuvant CT groups, respectively. RFS at 3 and 5 years was 51% and 38% in the observation group and 40% and 20% in the adjuvant CT group, respectively (P = .36). In univariate analysis, the significant prognostic factors associated with RFS were the number of LM (>or=10) and synchronous LM. Administration of adjuvant CT was not correlated with RFS. OS at 3 and 5 years was 90% and 76% in the observation group and 96% and 96% in the adjuvant CT group, respectively (P = .58).
  
  
  CONCLUSIONS
  RFS in patients receiving adjuvant CT was similar to that reported in the observation group and in historical cohorts without adjuvant CT. Thus, administration of streptozotocin-5-FU cannot be recommended in this indication.
authors.affiliation: Pôle des Maladies de l'Appareil digestif, Service de Gastroentérologie-Pancréatologie, Hôpital Beaujon, Clichy, France. frederique.maire@bjn.aphp.fr
authors.forename: Frédérique
authors.initials: F
authors.lastname: Maire
authors.forename: Pascal
authors.initials: P
authors.lastname: Hammel
authors.forename: Reza
authors.initials: R
authors.lastname: Kianmanesh
authors.forename: Olivia
authors.initials: O
authors.lastname: Hentic
authors.forename: Anne
authors.initials: A
authors.lastname: Couvelard
authors.forename: Vinciane
authors.initials: V
authors.lastname: Rebours
authors.forename: Magaly
authors.initials: M
authors.lastname: Zappa
authors.forename: Eric
authors.initials: E
authors.lastname: Raymond
authors.forename: Alain
authors.initials: A
authors.lastname: Sauvanet
authors.forename: Christophe
authors.initials: C
authors.lastname: Louvet
authors.forename: Philippe
authors.initials: P
authors.lastname: Lévy
authors.forename: Jacques
authors.initials: J
authors.lastname: Belghiti
authors.forename: Philippe
authors.initials: P
authors.lastname: Ruszniewski
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D018572:Disease-Free Survival; D004701:Endocrine Gland Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013311:Streptozocin / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D013311:Streptozocin; D005472:Fluorouracil