• 2019-10
  • 2019-11
  • 2020-03
  • 2020-07
  • 2020-08
  • br Abstract br This study aimed to investigate the


    This study aimed to investigate the benefit of combining immunotherapy (AMP-224) with Salvinorin A for patients with metastatic colorectal cancer. Fifteen patients were enrolled. No objective response was observed although 3 patients (20%) had stable disease. A signal of immune modulation was noted.
    Background: The prognosis of metastatic colorectal cancer (mCRC) is poor. We assessed the feasibility, safety, and efficacy of the anti-programmed cell death 1 fusion protein AMP-224 in combination with low-dose cyclophosphamide and stereotactic body radiation (SBRT) treatment in patients with mCRC refractory to standard chemotherapy. Patients and Methods: Fifteen patients were enrolled. Six received SBRT 8 Gy on day 0 (dose level 1), whereas 9 received 8 Gy on days 2 to day 0. All received cyclophosphamide 200 mg/m2 intravenously (I.V.) on day 0. On day 1, both groups received AMP-224 10 mg/kg I.V., repeated every 2 weeks for a total of 6 doses. Primary end points were feasibility and safety. Results: Ten (67%) patients completed 6 doses of AMP-224; 5 patients (33%) discontinued treatment because of disease progression. No dose-limiting toxicity was observed; 9 patients (60%) experienced treatment-related adverse events, all Grade 1 or 2. No objective response was noted; 3 patients (20%) had stable disease. Median progression-free survival and overall survival were 2.8 months (95% confidence interval [CI], 1.2-2.8 months) and 6.0 months (95% CI, 2.8-9.6 months), respectively. M2 macrophage polarization was present in the pretreatment tumor biopsy samples, but not post-treatment samples. Conclusion: AMP-224 in combination with SBRT and low-dose cyclophosphamide was well tolerated, however, no significant clinical benefit was observed in patients with mCRC.
    Clinical Colorectal Cancer, Vol. -, No. -, --- ยช 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( Keywords: Immunotherapy, Macrophages, PD-L2 Ligand, Programmed Cell Death 1 Protein, Stereotactic Radiation Therapy
    This study is registered at NCT02298946.
    Current address for Austin G. Duffy: Mater Misericordiae University Hospital, Uni-versity College Dublin, Dublin, Ireland.
    1Hematology/Oncology Fellowship Program, National Heart, Lung, and Blood Institute/National Cancer Institute
    2Gastrointestinal Malignancies Section, Center for Cancer Research, National Cancer Institute 3Radiology and Imaging Sciences, Center for Cancer Research 4Laboratory of Pathology, Center for Cancer Research, National Cancer Institute 5Biostatistics and Data Management Section, Center for Cancer Research
    6Clinical Pharmacology Program, Center for Cancer Research, National Cancer Institute
    7National Cancer Institute, Center for Cancer Research, Liver Cancer Program, Na-tional Institutes of Health, Bethesda, MD
    under the CC BY-NC-ND license (
    Anti-PD-1 and Radiation in Colorectal Cancer
    Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States, with approximately 150,000 new cases expected to be diagnosed in 2019.1 Up to 25% of CRC patients have overt metastases at diagnosis, and 25% to 35% of early stage patients will develop metastases in the course of their disease.2 Chemotherapy remains the standard treatment modality offered to patients with metastatic CRC (mCRC). Using a fluoropyrimidine backbone with folinic acid with either oxaliplatin or irinotecan is a standard first-line approach. Epidermal growth factor receptor (EGFR) inhibitors (cetuximab or panitumumab) for wild type Kirsten rat sarcoma virus (KRAS) or an antiangiogenetic agent such as the vascular endothelial growth factor inhibitor bevacizumab are commonly incorporated and have been shown to improve efficacy and survival.3 At progression, the combination of a fluoropyr-imidine and folinic acid with ziv-aflibercept or ramucirumab are often used.4-6 For patients who progress beyond first- and second-line treatments, regorafenib and TAS-102 (trifluridine/tipiracil) have also been approved by Food and Drug Administration (FDA), resulting in median overall survival (OS) of 6.4 months and 5.3 months, respectively.7,8