Is adjuvant therapy with streptozotocin and 5-fluorouracil useful after resection of liver metastases from digestive endocrine tumors?
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.
Maire
Frédérique
F
Pôle des Maladies de l'Appareil digestif, Service de Gastroentérologie-Pancréatologie, Hôpital Beaujon, Clichy, France. frederique.maire@bjn.aphp.fr
Hammel
Pascal
P
Kianmanesh
Reza
R
Hentic
Olivia
O
Couvelard
Anne
A
Rebours
Vinciane
V
Zappa
Magaly
M
Raymond
Eric
E
Sauvanet
Alain
A
Louvet
Christophe
C
Lévy
Philippe
P
Belghiti
Jacques
J
Ruszniewski
Philippe
P
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
D000970:Antineoplastic Agents; D013311:Streptozocin; D005472:Fluorouracil