Streptozocin/5-fluorouracil chemotherapy is associated with durable response in patients with advanced pancreatic neuroendocrine tumours.
BACKGROUND
The role of systemic chemotherapy for pancreatic neuroendocrine tumours (pNET) is controversially discussed. Objective response rates (RR) reported for streptozocin (STZ)-based chemotherapy are variable and novel targeted drugs have recently been approved. However, the sequence of treatment remains unclear. We aimed to evaluate the efficacy of STZ plus 5-fluorouracil (STZ/5-FU) in a large pNET cohort.


METHODS
Data from 96 pNET patients treated with STZ/5-FU were analysed retrospectively. Endpoints of the study were RR, time to tumour progression (TTP) and overall survival (OS).


RESULTS
Mean age of patients at the start of chemotherapy was 57.6years (range, 32.1-80.4). STZ/5-FU was the 1st line treatment in 56.3%. 11.5% had G1, 79.2% G2 and 6.3% G3 neoplasms. Baseline progression was evident in 74%. Objective response rate was 42.7%. 40.6% of patients showed stable disease as best response while 16.7% showed progressive disease. Treatment was discontinued due to toxicity in 16 patients. Median TTP and OS were 19.4 (95% confidence interval (CI), 13.6-25.2) and 54.8months (95% CI, 34.7-74.9), respectively. In Cox regression analysis, Ki67>15% was the only negative prognostic factor for TTP (hazard ratio (HR), 3.3; P<0.001), confirmed by multivariate analysis (HR, 6.7; P=0.001).


CONCLUSIONS
STZ/5-FU was associated with considerable RR. Treatment was associated with durable TTP especially in patients with Ki67-index of ⩽15%. These findings along with good tolerability strengthen the value of this two-drug chemotherapy for the management of unresectable pNET.
Dept. of Hepatology and Gastroenterology, Campus Virchow Klinikum, Charité Universitätsmedizin Berlin, Germany.
Lisa-Marie
LM
Dilz
Dept. of Radiology, Campus Virchow Klinikum, Charité Universitätsmedizin Berlin, Germany.
Timm
T
Denecke
Dept. of Nuclear Medicine, Campus Virchow Klinikum, Charité Universitätsmedizin Berlin, Germany.
Ingo G
IG
Steffen
Dept. of Nuclear Medicine, Campus Virchow Klinikum, Charité Universitätsmedizin Berlin, Germany.
Vikas
V
Prasad
Klinikum St. Marien, Dept. of Internal Medicine, Amberg, Germany.
Ludwig Fischer
LF
von Weikersthal
Dept. of Hepatology and Gastroenterology, Campus Virchow Klinikum, Charité Universitätsmedizin Berlin, Germany.
Ulrich-Frank
UF
Pape
Dept. of Hepatology and Gastroenterology, Campus Virchow Klinikum, Charité Universitätsmedizin Berlin, Germany.
Bertram
B
Wiedenmann
Dept. of Hepatology and Gastroenterology, Campus Virchow Klinikum, Charité Universitätsmedizin Berlin, Germany. Electronic address: marianne.pavel@charite.de.
Marianne
M
Pavel
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000188:drug therapy*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D012189:Retrospective Studies; D013311:Streptozocin / Q000008:administration & dosage; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D013311:Streptozocin; D005472:Fluorouracil
5-Fluorouracil; Chemotherapy; Ki-67; Neuroendocrine tumour; Objective response; Pancreas; Pancreatic neuroendocrine tumour; Streptozocin; Survival