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Salvage camrelizumab plus apatinib for relapsed esophageal neuroendocrine carcinoma after esophagectomy: a case report and review of the literature.

ABSTRACT: The current evidence regarding immunotherapy plus targeted therapy in esophageal neuroendocrine carcinoma (NEC) is lacking. Camrelizumab is a programmed cell death protein 1 inhibitor. Apatinib is a selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2. A 50-year-old female was initially diagnosed as primary esophageal NEC. Neoadjuvant chemotherapy and Ivor Lewis esophagectomy were performed (ypT3N0M0, stage Ⅱ). Twenty months after the surgery, an isolated mediastinal lymph node recurrence of NEC was recorded. The specimen revealed a positive expression of vascular endothelial growth factor and programmed cell death ligand 1. The diseased lymph node was slightly enlarged after two cycles of first-line paclitaxel liposome and S-1. Second-line apatinib and S-1 for 2 months also resulted in progressive disease. Subsequently, third-line camrelizumab plus apatinib was continued for 5 months. The patient demonstrated a progression-free status for more than 10 months following the combination therapy. Meanwhile, relevant studies of camrelizumab in gastric or esophageal cancer were briefly reviewed. Based on the current evidence, camrelizumab is a promising agent for esophageal cancer. More prospective trials are warranted before a definite recommendation could be drawn.

SUBMITTER: Liu L

PROVIDER: S-EPMC7678944 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Salvage camrelizumab plus apatinib for relapsed esophageal neuroendocrine carcinoma after esophagectomy: a case report and review of the literature.

Liu Lei L Liu Yuanyuan Y Gong Longbo L Zhang Miao M Wu Wenbin W

Cancer biology & therapy 20201023 11

The current evidence regarding immunotherapy plus targeted therapy in esophageal neuroendocrine carcinoma (NEC) is lacking. Camrelizumab is a programmed cell death protein 1 inhibitor. Apatinib is a selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2. A 50-year-old female was initially diagnosed as primary esophageal NEC. Neoadjuvant chemotherapy and Ivor Lewis esophagectomy were performed (ypT3N0M0, stage Ⅱ). Twenty months after the surgery, an isolated mediasti ...[more]

PMID: 33092443

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Project description:RationaleSmall cell carcinoma of the esophagus (SCCE) is an uncommon but lethal disease characterized by dismal prognosis. Only 10% of advanced SCCE patients survive longer than 1 year. Resection is a choice for limited-stage cases, whereas the optimal treatment regimen for primary SCCE is yet to be elucidated. To the best of our knowledge, the efficacy of S-1 plus apatinib for irinotecan-refractory SCCE has not been reported before.Patient concernsA 61-year old, previously healthy male was admitted for dysphagia and fatigue. Endoscopic biopsy revealed a tumor in the middle third of the esophagus. Further exams including abdomen computed tomography excluded distant metastasis.DiagnosesPrimary SCCE (pT1bN1M0, IIB) was established after salvage operation.InterventionsThe tumor was enlarged after 1 cycle of first-line chemotherapy using irinotecan plus cisplatin, which indicated drug resistance. Second-line oral apatinib (425 mg daily) plus S-1 (60 mg, twice daily for 4 weeks with a 2-week drug-free interval) for a month showed efficacy, as shown by decreased serum neuron-specific enolase and stable of the esophageal lesion. Thereafter, salvage minimally invasive Ivor-Lewis esophagectomy and 2-field lymph node dissection was performed, followed by oral apatinib plus S-1 at the prior dosage for 6 months. In addition, maintenance therapy using low-dose apatinib (250 mg daily) plus S-1 (40 mg, twice daily for 4 weeks with a 2-week interval) were administered for another 6 months. Then the patient was followed up irregularly at the outpatient clinic.OutcomesThe adverse events including hand-foot syndrome, hypertension, vomiting, leukopenia, impaired hepatic function, and fatigue were mainly tolerable. Forty months after the operation, he was readmitted for back pain and disseminated bone metastases appeared in magnetic resonance images. His progression-free survival could not be obtained precisely, and his overall survival was longer than 40 months up to September 2019.LessonsS-1 plus apatinib followed by a timely esophagectomy with curative intent might be an alternative option for chemotherapy-refractory SCCE in selected patients. Better evidence is warranted.

Project description:BackgroundMetastatic neuroendocrine carcinoma has an extremely poor prognosis, and no effective second-line treatment is available. Herein, we describe a case of multiple metastases after primary resection of esophageal neuroendocrine carcinoma successfully treated with nivolumab plus radiotherapy in a short time.Case presentationA man in his 70s presented to our hospital after an abnormality was detected on an upper gastrointestinal series. Upper gastrointestinal endoscopy revealed a type 2 tumor spanning the endothelial cell junction to the abdominal esophagus. Histopathological examination of the biopsy confirmed a diagnosis of esophageal neuroendocrine carcinoma. The patient had no distant metastases. Thoracoscopic esophagectomy with three-field lymph node dissection was performed. Histopathological examination confirmed a diagnosis of esophageal neuroendocrine carcinoma with features of adenoid cystic-like carcinoma and squamoid pattern (pT2 [MP], INF a, ly1, v1 [EVG], pIM0, pDM0, pRM0, pN1 [1/28], M0; Stage II), which was positive for synaptophysin. The postoperative course was good, with no complications. The patient was treated with 100 mg of irinotecan and 100 mg of cisplatin, administered every 4 weeks, as postoperative adjuvant chemotherapy. Grade 3 loss of appetite was observed, and adjuvant chemotherapy was discontinued after four cycles of first-line treatment. A positron emission tomography-computed tomography scan 3 years after surgery showed abnormal uptake in the subaortic, left hilar, and left axillary lymph nodes, and in a mass in the right lung apex. The patient was diagnosed with metastatic esophageal neuroendocrine carcinoma postoperatively. First-line treatment could not be repeated due to toxicity from the initial treatment. Nivolumab (240 mg every 2 weeks) was administered as second-line treatment, and radiotherapy was started (56 Gy delivered in 28 fractions to the local [subaortic and hilar] lymph nodes). After 10 cycles of nivolumab in combination with radiotherapy (56 Gy), a positron emission tomography-computed tomography scan showed disappearance of all lesions. A complete response was achieved. Maintenance therapy (240 mg of nivolumab) was continued. No recurrence has been observed for 42 months.ConclusionsWe experienced a case in which nivolumab in combination with radiotherapy was effective for metastatic esophageal neuroendocrine carcinoma after primary resection.

Project description:BackgroundExtra-pulmonary neuroendocrine carcinomas (EP-NECs) are rare, accounting for ~1/100,000 of NECs, aggressive neoplasms and poor prognosis. Sometimes, a non-neuroendocrine component is also accompanying these EP-NECs. Curative surgery is suggested for early stage patients while system chemotherapy and locoregional radiotherapy are considered for advanced inoperable disease. Nonetheless, there was lack of standard second-line treatment strategy. Herein, we report a case of NEC involving a large cell neuroendocrine carcinoma (LCNEC) and adenocarcinoma of the gallbladder treated with a surufatinib-containing regimen in the second-line treatment setting and establish the efficacy of this regimen in the treatment of EP-NECs.Case descriptionA 58-year-old male presented with symptoms such as distension in the upper right abdomen and a palpable mass. The abdominal magnetic resonance imaging (MRI) scan showed a giant soft tissue mass in the left lobe of the liver, and liver biopsy suggested LCNEC with a non-neuroendocrine (NNE) component. Based on the available literature, a first-line therapy of oxaliplatin + gemcitabine + camrelizumab + apatinib was started initially; however, there was rapid tumor progression. Thus, a second line of treatment was started, where apatinib was replaced with surufatinib, which was given along with oxaliplatin and camrelizumab and continued for seven complete cycles. The patient was re-examined with MRI, which showed a significant decrease in tumor size. And a partial response was achieved. Main adverse events included hand and foot numbness, hypertension, proteinuria, hematuria, and hyperthyroidism. The patient underwent surgery after the second line of treatment and the post-operative pathology report revealed the presence of LCNEC and adenocarcinoma of the gallbladder. Two months later, re-examination result showed no tumor recurrence.ConclusionsAs yet, the criteria strategy for unresectable EP-NECs to improve survival outcomes is scarce. EP-NECs are badly in need of effective second-line therapy to carry out survival benefits after resistance to first-line regimen. The case report demonstrated that a surufatinib-containing regimen including oxaliplatin and camrelizumab could be an effective treatment strategy for the second-line treatment of EP-NECs. Furthermore, this strategy is well tolerated and treatment-related toxicity are manageable. More clinical trials are warranted to further confirm the efficacy.

Dataset Information

Salvage camrelizumab plus apatinib for relapsed esophageal neuroendocrine carcinoma after esophagectomy: a case report and review of the literature.

Publications

Salvage camrelizumab plus apatinib for relapsed esophageal neuroendocrine carcinoma after esophagectomy: a case report and review of the literature.

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