P-206 - Efficacy and tolerance of a simplified combination of Streptozotocin and epi-adriamycin in metastatic foregut neuroendocrine tumor (NET)

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Anti-Cancer Agents & Biologic Therapy
Neuroendocrine Cancers
Presenter L. Hirsch
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors L. Hirsch, J. Taieb, C. Lepere, J.-. Vaillant, S. Louafi, S. Pernot, B. Landi, A. Zaanan, P. Rougier
  • Universite Paris-V European Hospital Georges Pompidou, Paris/FR

Abstract

Introduction

Since more than 30 years the combinations of adriamycine (A) and streptozotocine (STZ) is considered as one of the standard chemotherapy regimens (Moertel et al, N Engl J Med 1992, 326 : 519-23) and proposed to patients with aggressive grade 2 metastatic pancreatic NET (PNET). This combination has many drawbacks: as an heterogeneous response rate (from 25% to 67%), an overall survival which depends on many factors and range from 11 to 19 months, and a poor tolerance when using the classical 5 days ‘schedule of administration every 6 weeks with frequent nausea and vomiting. To overcome these limits since 2011 we have developed a simplified 2 days ‘regimen repeated every 3 weeks.

Methods

The aim of the study was the evaluation of the tolerance and efficacy of this simplified schedule used in patients suffering from progressive metastatic PNET. This simplified regimen used an equivalent dose/intensity of epi-A and STZ as in the Meortel regimen; it results in an every 3 weeks administration of STZ: 600 mg/m2 in 1 hour perfusion d1 and d2 and Epi-A: 60 mg/m2 d1 with normal hydration and anti-emetics (anti-HT3) until progression, surgery or toxicity.

Results

Between 2011 January and 2014 December 8 patients have been treated with this regimen and their data prospectively entered in the hospital data-base have been retrospectively analyzed. According to the French law it was allowed to review data of all patients who gave their consent when they were treated. Median age was 64 years (34 – 80 year); sex: female: 2 male: 6; PS: 0/1/2 =2/3/3; all were well differentiated PNET: Ki67 gr 2 (2 -20%): 7/8 and 1 gr3 (22%); tumor location: 3 NET were in the head of the pancreas and 4 in the tail and 1 was a gastric NET; all were metastatic: liver only: 6/8, liver + bone + lymph node (LN): 1/8, liver + LN: 1/8. Median number of cycles administered were 3 (1 – 7); with 2 patients who received only 1 and 3 cycles and move to 5FU and STZ for toxicity (1 for atrial fibrillation under Epi-A).

Tolerance has been good for STZ: with no renal toxicity; only 1/8 gr 3 vomiting; 1/8 gr 3 neutropenia: 1/8 gr 3 asthenia: and no dose reduction has been necessary. Efficacy: there were 4 objective response (RECIST 1-1) and 2 stabilization; only 2 patients progressed. After chemotherapy 2 patients have been operated and had their primary resected allowing secondarily a local treatment of their liver metastases by chemoembolization

Conclusion

Compared to the traditional regimen of adriamycin and STZ on five days the simplified regimen on 2 days every 3 weeks appeared to have a favorable profile. This combination warrant to be evaluated prospectively in a controlled trial.