| Eligibility |
Inclusion Criteria:
- Age >/= 18 years;
- Male or Female;
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
- Histologically or cytologically confirmed locally advanced adenocarcinoma of esophagus
or gastroesophageal junction (Siewert type I/II);
- Human epidermal growth factor receptor 2 (HER2)-negative tumors;
- Clinical staging cT2-T4aNanyM0 or TanyN+M0 (UICC/AJCC 8th edition), potentially
resectable disease;
- Adequate hematologic and end organ function based on laboratory results obtained
within 14 days prior to initiation of study treatment;
- For women of childbearing potential: agreement to remain abstinent;no evidence of
pregnancy within 72 hours before the start of study regimen;
- Must be willing and able to provide written informed consent.
Exclusion Criteria:
- Known unresectable disease,cT4b disease invading aorta or trachea;
- Known distant metastases,including supraclavicular lymph nodal disease;
- Uncontrollable pleural or pericardial effusion,or ascites requiring repeated
interventions;
- Prior chemotherapy, immunotherapy, targeted therapy, thoracic radiotherapy or prior
surgical resection for an esophageal tumor;
- Poor nutritional status, BMI < 18.5 Kg/m2; if symptomatic nutritional support is
corrected before randomization, enrollment may continue to be considered after
assessment by the principal investigator;
- History of allergy to biological drugs produced by Chinese hamster ovary cells, any
component of toripalimab, tegafur, oxaliplatin or other platinum drugs;
- History of severe allergic, allergic reactions, or other hypersensitivity to chimeric
or humanized antibodies or fusion proteins;
- Patients with prior malignancies are eligible if they have been disease-free for > 5
years and are deemed by their physician to be at low risk for recurrence. Patients
with squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma in situ
of the cervix, or carcinoma in situ of the colon or rectum that have been effectively
treated are eligible, even if these conditions were diagnosed within 5 years prior to
enrollment;
- History of any active autoimmune disease or autoimmune disease, including myasthenia
gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid
arthritis, inflammatory bowel disease, antiphospholipid syndrome-related vascular
thrombosis, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome,
multiple sclerosis, vasculitis, glomerulonephritis, etc.; hypothyroidism (hormone
replacement therapy can be considered to be included);
- History of immunosuppressive drugs, or systemic hormones used to achieve
immunosuppressive purposes (dose > 10 mg/day prednisone or equivalent dose) within 2
weeks before the first use of the study drug; in the absence of active autoimmune
diseases, inhaled or local steroids are allowed and doses > 10 mg/day prednisone or
equivalent doses of adrenocorticotropic hormone replacement;
- History of type 1 diabetes, whose blood glucose is controlled after treatment with a
stable dose of insulin dosing regimen may be enrolled in this study;
- History of live attenuated vaccines are received within 4 weeks before the first use
of the study drug;
- History of major surgery or severe trauma within 4 weeks before the first use of the
study drug;
- History of eczema, psoriasis, lichen simplex chronicus, or dermatologic manifestations
of vitiligo (eg, patients with psoriatic arthritis were excluded from the study) were
permitted to enroll in this study if they met the following conditions: a) had rash
coverage less than 10% of body surface area (BSA); b) had adequately controlled
disease at baseline and required only low-potency topical steroid therapy; c) did not
have an acute exacerbation of the underlying disease within the past 12 months without
the need for PUVA (psoralen plus ultraviolet A radiation), methotrexate, retinoids,
biologics, oral calcineurin inhibitors, high-titer, or oral steroid therapy for];
- History of idiopathic pulmonary fibrosis, organizing pneumonia (such as bronchiolitis
obliterans), drug-induced pneumonia, idiopathic pneumonia, interstitial pneumonia, or
evidence of active pneumonia on screening chest CT scan;
- History of immunodeficiency, including HIV test positive, or suffering from other
acquired or congenital immunodeficiency diseases, or a history of organ
transplantation or allogeneic bone marrow transplantation;
- Uncontrolled cardiac clinical symptoms or diseases, including but not limited to: a)
NYHA class II or higher heart failure; b) unstable angina; c) myocardial infarction
within 1 year; d) clinically significant supraventricular or ventricular arrhythmia
that remains poorly controlled without or after clinical intervention.
- Known hereditary or acquired bleeding and thrombophilia (such as hemophilia,
coagulation dysfunction, thrombocytopenia, etc.);
- Known serious infection (CTCAE > 2) within 4 weeks before the first use of the study
drug, such as severe pneumonia requiring hospitalization, bacteremia, infectious
complications, etc.; baseline chest imaging showed active pulmonary inflammation,
symptoms and signs of infection within 14 days before the first use of the study drug
or oral or intravenous antibiotics, except for the prophylactic use of antibiotics;
- Active pulmonary tuberculosis infection detected by medical history or CT examination,
or history of active pulmonary tuberculosis infection within 1 year before enrollment,
or history of active pulmonary tuberculosis infection more than 1 year ago but without
regular treatment;
- Active hepatitis B (HBV DNA = 2000 IU/mL or 104 copies/mL), hepatitis C (hepatitis C
antibody positive, and HCV RNA above the lower limit of detection of the analytical
method);
- Pregnant or lactating women;
- Other factors that may lead to forced halfway termination of the study as judged by
the investigator, such as having other serious diseases (including mental illness)
requiring concomitant treatment, alcoholism, drug abuse, family or social factors that
may affect the safety or compliance of the subject.
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