Prospective phase II study of capecitabine and temozolomide (CAPTEM) for progressive, moderately, and well-differentiated metastatic neuroendocrine tumors.

Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Session Type and Session Title: 
General Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Oral Abstract Session: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract (eQ&A)
Abstract Number: 
J Clin Oncol 32, 2014 (suppl 3; abstr 179)
Robert Lance Fine, Anthony Paul Gulati, Dawn Tsushima, Kelley B. Mowatt, Anna Oprescu, Jeffrey N. Bruce, John A. Chabot; Columbia University, New York, NY; Columbia University Medical Center, New York, NY; Columbia University College of Physicians and Surgeons, New York, NY

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: We found in our lab that capecitabine (CAP), the prodrug of 5-FU, and temozolomide (TEM) were synergistic in inducing apoptosis in BON neuroendocrine tumor (NET) cell lines. We were the first to report in 2004 the use and mechanism of action of CAP and TEM (CAPTEM) in well differentiated NETs with promising results. Here we describe the interim analysis of an ongoing Phase II trial. Methods: 28 patients with metastatic well-moderately differentiated NET (ki-67 ≤20%) who had shown progression only on 60mg Sandostatin LAR (if octreotide scan positive) were treated with the following regimen: CAP 1,500mg/m2/day (PO divided BID, maximum 2,500 mg/day) on d1-14, and TEM 150-200mg/m2/day (PO divided BID, lower dose for patients who had prior chemotherapy or extensive radiation) on d10-14, with the next two weeks off, in a 28 day cycle. Primary objective was RR based upon RECIST, and secondary objectives included PFS, OS (from time of initiation of therapy), and toxicity evaluation. Other inclusion criteria were: age <80, ECOG PS 0-2, and adequate hematologic, renal, and liver function, and failure on high dose Sandostatin LAR. Results: 28 of 38 planned patients were enrolled with various NET subtypes (table). Overall RR was 43% (11% CR) and SD rate was 54%, with clinical benefit in 97%. ORR was 41% in carcinoid tumors. Ongoing mPFS is >20mo for all subtypes with 18/28 (64%) having progressed at this time. Twelve of 28 had died at this analysis with ongoing mOS of >25.3mo. The most common G3/4 toxicities were lymphopenia (32%), hyperglycemia (15%, unlikely related), thrombocytopenia (3%), and diarrhea (3%). No hospitalizations, opportunistic infections, or deaths occurred from CAPTEM. Conclusions: CAPTEM is an effective treatment for patients with progressive NET who failed high dose octreotide, with high PR and SD rates in carcinoids and insulinomas. The ongoing PFS in pancreatic NETs (>18.2 mo) is 150% greater than reported with everolimus and sutent. Clinical trial information: NCT00869050.

Number # SD % SD # PR % PR # CR %CR # PD mPFS
Carcinoid (typical
and atypical)
12 7 58% 4 33% 1 8% 0 >22
Pituitary 3 0 0% 1 33% 2 67% 0 >37.7
PNET 11 6 55% 4 45% 0 0% 1 >18.2
Medullary thyroid 2 2 100% 0 0% 0 0% 0 >22.1
Total 28 54% 32% 11% >20