Capecitabine, Oxaliplatin, Irinotecan, and Bevacizumab Combination Followed by Pazopanib plus Capecitabine Maintenance for High-Grade Gastrointestinal Neuroendocrine Carcinomas

Constantinos E. Alifieris*, John Griniatsos, Spiros G. Delis, Michail Nikolaou, Constantinos Avgoustou, Mihalis I. Panagiotidis, Eleni Souferi-Chronopoulou, Dimitrios T. Trafalis

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Objectives:Gastrointestinal neuroendocrine carcinoma (NEC) is a lethal, uncommon, and understudied neoplasm. We present the efficacy and safety of first-line capecitabine (CP), oxaliplatin, irinotecan, and bevacizumab (CAPOXIRI-BEV) combination followed by pazopanib plus CP maintenance therapy in patients with advanced high-grade poorly differentiated gastrointestinal NEC.Methods:This was a two-stage phase II study conducted at multiple institutions. Patients were consecutively enrolled and had advanced NEC of the colon or small bowel. Patients received irinotecan 125 mg/m2, oxaliplatin 80 mg/m2on day 1, CP 1000 mg/m2twice daily on days 1 to 14, plus bevacizumab 8 mg/kg on day 1 for six 21-day cycles. Maintenance therapy was given to those who responded (complete response/partial response) or had stable disease after 6 cycles with CAPOXIRI-BEV with pazopanib 800 mg daily plus CP 1600 mg/m2daily on days 1 to 14 every 3 weeks until disease progression or unacceptable toxicity. Patients who progressed on CAPOXIRI-BEV received standard etoposide-carboplatin. The primary endpoint was overall response rate.Results:Twenty-two patients were enrolled of whom 19 were evaluable. The median age was 60 years. The overall response rate (3 complete response/6 partial response) was 47.4% (95% confidence interval: 29.5-76.1), the overall disease control rate was 78.9% (95% confidence interval: 62.6-99.6), and, at median 30 (11 to 41 mo) months' follow-up, 5 patients (26.3%) were still alive. Median progression-free survival was 13 months, and the 1-year progression-free survival rate was 52.6%. The median overall survival was 29 months. The median overall survival of the 9 patients who responded versus those with stable disease/progressive disease was 30.5 versus 14 months, respectively. The median duration of response was 16 months. Predictable toxicity was observed.Conclusions:First-line CAPOXIRI-BEV followed by pazopanib plus CP maintenance therapy for advanced NEC demonstrates promising efficacy and predictable toxicity. Further investigation is warranted.

Original languageEnglish
Pages (from-to)305-310
Number of pages6
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume43
Issue number5
DOIs
Publication statusPublished - 1 May 2020

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