TY - JOUR
T1 - Capecitabine, Oxaliplatin, Irinotecan, and Bevacizumab Combination Followed by Pazopanib plus Capecitabine Maintenance for High-Grade Gastrointestinal Neuroendocrine Carcinomas
AU - Alifieris, Constantinos E.
AU - Griniatsos, John
AU - Delis, Spiros G.
AU - Nikolaou, Michail
AU - Avgoustou, Constantinos
AU - Panagiotidis, Mihalis I.
AU - Souferi-Chronopoulou, Eleni
AU - Trafalis, Dimitrios T.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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.
AB - 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.
KW - bevacizumab
KW - carcinoma
KW - neuroendocrine
KW - pazopanib
KW - tumor
UR - http://www.scopus.com/inward/record.url?scp=85084107498&partnerID=8YFLogxK
U2 - 10.1097/COC.0000000000000668
DO - 10.1097/COC.0000000000000668
M3 - Article
C2 - 32343515
AN - SCOPUS:85084107498
SN - 0277-3732
VL - 43
SP - 305
EP - 310
JO - American Journal of Clinical Oncology: Cancer Clinical Trials
JF - American Journal of Clinical Oncology: Cancer Clinical Trials
IS - 5
ER -
