| Eligibility |
Inclusion Criteria:
1. 18=age=75.
2. Histologically or cytologically confirmed esophageal squamous carcinoma.
3. Patients must have unresectable disease as assessed by thoracic surgeons or refuse
surgical treatment.
4. The investigator confirmed at least one measurable lesion according to RECIST 1.1.
5. Stage II-IVA (AJCC 8th)
6. No adjacent organs infringed confirmed by endoscopic ultrasonography (T1-3).
7. ECOG PS 0-1.
8. FEV1>0.8L
9. Life expectancy is not less than 12 weeks.
10. No prior chemotherapy, radiotherapy, biotherapy, immunotherapy or other anti-tumor
treatment for esophageal cancer.
11. Adequate organ function defined at baseline as: 1) ANC =1.5×109 /L,PLt =100×109 /L,Hb
=90 g/L; 2) TBIL =1.5×ULN, ALT =2.5ULN, AST =2.5ULN, BUN and Cr =1×ULN or Ccr
=50ml/min (Cockcroft-Gault formula); 3) INR =1.5×ULN or PT =1.5×ULN (If the patient is
receiving anticoagulant therapy, PT should be within the intended use range of the
anticoagulant drug); 4) Myocardial zymogram is within normal range.
12. Women of childbearing age must have taken reliable contraceptive measures or have a
pregnancy test (serum or urine) within 7 days prior to enrollment and the results are
negative. Besides, subjects should agree to use effective methods of contraception
during the trial and within 2 months of the last dose of anti-PD-1 antibody. For male
subjects whose spouse are of childbearing age, effective contraceptive methods should
be used during the trial and within 2 months after the last dose of anti-PD-1
antibodies;
13. Subject volunteers to join the study, Signs informed consent, has good compliance and
can cooperate with follow-up.
Exclusion Criteria:
1. Those with prior or concurrent uncured malignant tumor. cured skin basal cell
carcinoma, cervical cancer and superficial bladder cancer were excluded.
2. Esophageal cancer patients with primary multifocal lesions.
3. Those with the pathology of small cell esophageal carcinoma, esophageal adenocarcinoma
or mixed carcinoma.
4. Primary esophageal squamous carcinoma with active hemorrhage of the primary lesion
within 2 months.
5. Those with primary esophageal lesion that was closely related to tracheal bronchus and
great vessels, and were evaluated with a great risk of perforation and massive
bleeding by the researchers.
6. Patients with any active autoimmune disease or autoimmune disease history (such as
interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis,
myocarditis, nephritis, hyperthyroidism, and hypothyroidism (those with normal thyroid
function after hormone replacement therapy could be enrolled); those with leucoderma
or childhood asthma that was completely relieved and required no intervention during
adulthood could be enrolled, while asthma patients requiring bronchodilators and
medical intervention should not be enrolled.
7. Patients with uncontrolled cardiovascular disease: grade II and above myocardial
ischemia or myocardial infarction, and poorly-controlled arrhythmia (including the QTc
interval of =470 ms); those with grade III-IV cardiac insufficiency according to the
NYHA criteria, or those whose echocardiography revealed left ventricular ejection
fraction (LVEF) of <50%; and those having myocardial infarction within 1 year.
8. Those with active infection or fever of >38.5 ? with unknown cause during the
screening period and before the first administration (patients with tumor-induced
fever judged by the researchers could be enrolled).
9. Those with interstitial lung disease or active non-infectious pneumonia history or
evidence.
10. Those with congenital or acquired immunodeficiency (such as those with HIV infection),
active hepatitis B (HBV-DNA=104 copies/ml) or hepatitis C (positive hepatitis C
antibody, and the HCR-RNA was higher than the lower limit of detection of the analysis
method).
11. Those who had previously received other PD-1 antibody treatment or PD-1/PD-L1 targeted
immune therapy.
12. Those who were known to be allergic to paclitaxel, carboplatin, macromolecular protein
preparation, or any anti-PD-1 antibody component.
13. Subjects who required to use corticosteroids (prednison dose of > 10 mg/day) or other
immunosuppressors for systemic treatment within the first 7 days of research. In the
absence of active autoimmune disease, glucocorticoids at physiological dose (= 10
mg/day prednison or equivalent drug), inhalation or local application of steroid and
adrenocortical hormone replacement treatment with prednison at the dose of > 10
mg/day.
14. Those receiving anti-tumor monoclonal antibody (mAb) and targeted small molecule
treatment within 4 weeks before the initial use of the research drug, or those with
unrecovered adverse events induced by the previous treatment (namely, grade = 1 or
reaching the baseline level). Apart from subjects with = grade 2 nervous lesion or =
grade 2 alopecia, any subject that had received major surgery should sufficiently
recover from the toxic reaction and/or complication resulted from the surgical
intervention before the initiation of treatment.
15. Those who were within 4 weeks before the initial use of the research drug (subjects
that had entered the follow-up period were calculated at the final use of experimental
drug or instrument) or those who were participating other clinical research.
16. Patients should be inoculated with live vaccine within 4 weeks before the initial use
of research drug, inactivated viral vaccine specific to seasonal influenza for
injection was allowed, but the nasal use of live attenuated influenza vaccine was not
allowed.
17. Pregnant women or breast-feeding women.
18. Subjects who had other factors that might force them to terminate the research ahead
of time, such as the development of other severe disease (including mental disease)
that required combined treatment, seriously abnormal laboratory examination value, and
family or social factors that might affect the subject safety or experimental data
collection, as judged by the researchers.
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