The Clinical Efficacy Of Cetuximab Combined With PF Regimen In The Treatment Of Advanced Esophageal Cancer

The prognosis of esophageal cancer is very poor, the 5-year survival rate is only 14%, recurrence and metastasis are the main reasons for the survival of patients. Chemotherapy is the first choice in the treatment of advanced esophageal cancer, but there is no standard first-line chemotherapy regimen. Cisplatin combined with 5-fluorouracil(PF regimen) is a recognized standard chemotherapy regimen for advanced esophageal squamous cell carcinoma. However, response rates are low at 15%~45% and median survival is usually shorter than 8 months. Preclinical data showed that cetuximab enhanced the antitumor effect of chemotherapy and, in particular, augmented the activity of cisplatin. And cetuximab has shown significant efficacy in the treatment of metastatic colorectal cancer, non-small cell lung cancer and advanced head and neck cancer. Therefore, it was reasoned that cetuximab combined with chemotherapy may be an effective scheme in the treatment of advanced esophageal cancer. ObjectiveAt present, there is little research about cetuximab combined with chemotherapy as first-line therapy of advanced esophageal cancer. The efficacy of cetuximab in the treatment of advanced esophageal cancer is not clear. So we designed a retrospective study to compare the efficacy and adverse reactions of cetuximab combined with PF regimen and PF regimen alone as the first-line therapy for advanced esophageal cancer patients, and analysis the correlation between the rash degree and curative effect of cetuximab in the treatment. The goal of the retrospective study is to evaluate the efficacy and safety of cetuximab combined with PF regimen as the first-line therapy for advanced esophageal cancer, and provide some useful references for the further large-scale clinical studies. MethodsWe retrospectively analyzed 30 cases of untreated advanced esophageal cancer patients(clinical stage IV) as group A, who had been treated with cetuximab combined with PF regimen in Shandong Tumor Hospital from June 2011 to June 2015. And we also analyzed 35 cases of untreated advanced esophageal cancer patients(clinical stage IV) as group B, who had been treated with PF regimen alone during the same period. All patients accepted PF regimen(Cisplatin 75~100mg/m2, intravenous infusion on days 1~3; 5-fluorouracil 750mg/m2, continuous intravenous infusion of 24 hours daily on days 1~5, cycled every 21 days). Patients of group A also received cetuximab(an initial dose of 400mg/m2 on day 1 over 120 min, followed by weekly doses of 250 mg/m2 over 60 min). In group A, the number of chemotherapy cycles was 2~8, the median number was 4.5, continuous used of cetuximab for 3~20 weeks, the median number was 9 weeks; In group B, the number of chemotherapy cycles was 2~8, the median number was 4. The content of analysis included response rate(RR), disease control rate(DCR), progression free survival(PFS) and treatment-related adverse reactions of patients of two groups.We also analyzed the correlation of rash degree and curative effect after the treatment of cetuximab. All statistics were completed with SPSS17.0 software, the rate of the comparison was analyzed by chi-square test or Fisher’s exact test; progression free survival was analyzed by Kaplan-Meie method, the difference between two groups was analyzed by Log-rank test; the difference was statistically significant(P<0.05). Results1. Efficacy: RR was 33.3%, DCR was 83.3%, median PFS was 5.9 months(95% CI 4.8~7.0 months) in group A; RR was 25.7%, DCR was 51.4%, median PFS was 3.3 months(95% CI 2.9~3.7 months) in group B. After statistical analysis, the differences in RR between group A and group B had no statistical significance(P>0.05),but the differences of PFS and DCR had statistical significance(P<0.05).2. Adverse reaction: The major hematological toxic effects were decreased hemoglobin, neutrophil and thrombocytopenia; the nonhematological toxic effects mainly included diarrhea, nausea, vomiting, fever, fatigue, alopecia, neurotoxicity and rash. The vast majority of adverse reactions were mild, mainly I to II degree, so all the patients can tolerate them. The occurred rates of rash were 80% and 0% in group A and group B, and the difference was statistically significant(P<0.05). The occurred rates of decreased neutrophil, diarrhea, nausea and vomiting in group B were higher than in group A, and the differences were statistically significant(P<0.05); but they were rarely serious, mainly I to II degree, and they didn’t affect the continued treatment after symptomatic treatment. The other adverse reaction rates’ differences had no statistical significance(P >0.05).3. Correlation between the rash degree and curative effect: RR was 26.3%, DCR was 84.2%, median PFS was 5.9 months(95% CI 3.2~8.6 months) in 0~Ⅰdegree of rash group; RR was 45.5%, DCR was 81.8%, median PFS was 6.1 months(95% CI 4.5~7.7 months) in II ~ III degree of rash group, but the differences had no statistical significance(P >0.05). Conclusions1. Cetuximab combined with PF regimen compared to PF regimen only in the first-line treatment of advanced esophageal cancer can significantly improve the clinical efficacy. And that, Cetuximab combined with PF regimen won’t increase chemotherapy-related toxicity and the patient was well tolerated.2. There was no correlation between the rash degree and curative effect after the treatment of Cetuximab.