Τίτλος:
Capecitabine, Oxaliplatin, Irinotecan, and Bevacizumab Combination Followed by Pazopanib plus Capecitabine Maintenance for High-Grade Gastrointestinal Neuroendocrine Carcinomas
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2020 Lippincott Williams and Wilkins. All rights reserved.
Συγγραφείς:
Alifieris, C.E.
Griniatsos, J.
Delis, S.G.
Nikolaou, M.
Avgoustou, C.
Panagiotidis, M.I.
Souferi-Chronopoulou, E.
Trafalis, D.T.
Περιοδικό:
AMERICAN JOURNAL OF CLINICAL ONCOLOGY - CANCER CLINICAL TRIALS
Εκδότης:
Lippincott Williams and Wilkins
Λέξεις-κλειδιά:
alkaline phosphatase; amylase; bevacizumab; capecitabine; carboplatin; etoposide; irinotecan; oxaliplatin; pazopanib; antineoplastic agent; bevacizumab; capecitabine; irinotecan; oxaliplatin; pazopanib; pyrimidine derivative; sulfonamide, abdominal pain; adult; aged; anemia; anorexia; Article; asthenia; bleeding; body weight loss; cancer combination chemotherapy; cancer control; cancer growth; clinical article; constipation; deep vein thrombosis; diarrhea; drug efficacy; drug safety; edema; fatigue; febrile neutropenia; female; follow up; gastrointestinal carcinoma; hand foot and mouth disease; headache; human; hyperbilirubinemia; hypertension; hypokalemia; leukopenia; lung hemorrhage; lung infection; maintenance therapy; male; middle aged; mucosa inflammation; multiple cycle treatment; nausea; neuroendocrine carcinoma; neutropenia; overall response rate; overall survival; pancreatitis; phase 2 clinical trial; progression free survival; proteinuria; side effect; thrombocytopenia; thromboembolism; tinnitus; treatment response; vertigo; vomiting; carcinoma; clinical trial; gastrointestinal tumor; mortality; multicenter study, Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Capecitabine; Carcinoma, Neuroendocrine; Female; Gastrointestinal Neoplasms; Humans; Irinotecan; Male; Middle Aged; Oxaliplatin; Progression-Free Survival; Pyrimidines; Sulfonamides
DOI:
10.1097/COC.0000000000000668
