The efficacy and safety of the capecitabine/temozolomide (CAPTEM) regimen in the treatment of well-differentiated neuroendocrine tumors with liver metastasis after failure of previous therapy: Columbia University Medical Center experience.

Abstract

308 Background: We have observed efficacy and tolerability of the CAPTEM regimen in pNET. We conducted a retrospective review of patients with liver metastasis from any NET, including carcinoid, who were treated with this regimen at our institution between 2002-2008. Methods: We identified patients with neuroendocrine tumors who demonstrated progressive liver metastasis while on treatment with long-acting octreotide (up to 60mg/month) and were then treated with CAPTEM as per our institutional protocol. Patients received capecitabine for 14 days at 1000mg PO bid with temozolomide at 150 or 200mg/m2 in bid dosing on days 10-14 of each 28 day cycle. All patients had contrast enhanced CT or MRI, response was assessed by a radiologist utilizing RECIST 1.0 criteria. Results: We identified 18 patients (50% female, median age- 55), 9 had pNET (2 functional, 7 non-functional), 2 had MEN1, 4 had carcinoid (1 functional), 2 with gastrinoma and 1 with glucagonoma. All patients had Ki-67 <10%, 11 patients (61%) had received previous chemotherapy (median of 2 regimens), and 50% had previous chemoembolization. Performance status at time of enrollment was 0-2 (5 patients, 28% with PS-2.)The response rate in the population was 61% (11/18) with 1 CR and 10 PR by RECIST 1.0 criteria. Stable disease was seen in 4 (22%) patients and clinical benefit (CR+PR+SD) in 83%. Response was noted in carcinoid patients (2 of 4, with 1 CR and 1 PR in this group) and in MEN1 patients (1 of 2 with PR). Median PFS was 14.0 months (range 4.2-18 months). Treatment was well tolerated; the most common grade 1/2 toxicities were lymphopenia (50%) and neutropenia (44%), 1 patient had hand-foot syndrome. Grade 3 thrombocytopenia was observed in 2 patients (11%), there was no other grade 3 or 4 toxicities. Conclusions: The CAPTEM regimen is well tolerated and is associated with a significant response in patients with liver metastasis from NET including the difficult to treat cases of carcinoid and MEN1. A prospective Phase II trial of this regimen is ongoing.