Abstract Objective To study paclitaxel and cisplatin, fluorouracil (PCF) in the treatment of advanced gastric cancer efficacy and safety. Methods Retrospective analysis of the Beijing Union Medical College Hospital, Department of Medical Oncology admitted from November 2002 to November 2006 all PCF chemotherapy in patients with advanced gastric cancer, a total of 35 cases. Chemotherapy regimens: paclitaxel (PTX) 150mg/m2 intravenous infusion 3h, 1 day administration; cis-platinum (DDP) 12mg/m2 intravenous infusion, 1 to 5 days; fluorouracil (5-Fu) 3000mg/m2 continuous infusion 120h; every 21 days. 2 to 6 cycles of chemotherapy, respectively evaluable for response according to RECIST criteria, NCI CTC standard evaluation of toxic side effects. The results of 15 patients with locally advanced gastric cancer patients, postoperative the PCF adjuvant chemotherapy, the median progression-free survival time (PFS) 11.0 months, and median overall survival (OS) 18.6 months. 20 cases of distant metastases in patients with gastric cancer, 15 patients evaluable and CR 0 cases (0), partial remission (20%), stable disease in 9 cases (60%), disease progression, 3 patients (20%). The median time to disease progression (TTP) was 7.0 months, and median overall survival time (OS) 9.0. 3/4 adverse reactions were nausea (18.1%), neutropenia (9.4%) and fatigue (7.9%). 9.5% of patients with neutropenia fever. Adverse conclusion PCF program can be tolerated, the efficacy worthy of further study.
Key words advanced gastric cancer paclitaxel-cisplatin-fluorouracil
Gastric cancer is a common cancer of the digestive tract, particularly in China, already the Following lung cancer and liver cancer, the third most common cancer in gastric cancer patients newly issued annually 40 million people. Although the the worldwide gastric overall incidence is declining, but the mortality rate has been ranked second of all tumors, gastric cancer deaths each year in China up to 30 million people. Gastric occult onset, early, often without obvious symptoms, about 50% of the patients when the doctor is already in late. The gastric overall 5-year survival rate is about 15% to 20% Ⅲ B or Ⅳ patients less than 10% . Treatment of advanced gastric cancer chemotherapy, the traditional program fluorouracil, cisplatin or doxorubicin, but the effective rate is low, only 20% to 30%, the median survival time of 5-6 months [2 ]. The key to explore new and effective program to become the treatment of advanced gastric cancer. Beijing Union Medical College Hospital, Department of Medical Oncology in the past four years with paclitaxel, fluorouracil and cisplatin in the treatment of advanced gastric cancer patients with clinical data were retrospectively analyzed.
1 Materials and Methods
1.1 Clinical data
November 2002 to November 2006, the Beijing Union Medical College Hospital, Department of Medical Oncology admitted paclitaxel, fluorouracil, and cisplatin in the treatment of locally advanced or metastatic gastric cancer patients. A total of 35 cases, including 24 males and 11 females, the male to female ratio of 2.2:1. Aged 27 to 70 years, mean age 53.9 years, with a median age of 55 years old. ECOG score: 0 points 17 cases (49%), 14 cases (40%), 2 minutes, 4 cases (11%).
1.2 Case Features
Tumor site: esophagogastric junction 13 cases, 13 cases of gastric body, antrum eight cases, leather stomach one cases. Pathological types: squamous cell carcinoma, adenocarcinoma, 34 cases; five cases of adenocarcinoma mucinous adenocarcinoma, 8 cases of signet ring cell carcinoma. Degree of differentiation: well differentiated in 1 case (2.8%), in the differentiation of the two cases (5.7%), poorly differentiated in 29 cases (82.8%), 3 cases of an unknown degree of differentiation. Tumor stage: 15 patients with locally advanced (Ⅲ or Ⅳ, M0), 20 cases of distant metastases in patients with gastric cancer (Ⅳ stage M1).
1.3 PCF program
Paclitaxel (PTX) 150mg/m2 intravenous infusion 3h, 1 day administration; cis-platinum (DDP) 12mg/m2 intravenous infusion, 1 to 5 days; fluorouracil (5 Fu) 3000mg/m2, continuous intravenous infusion Note 120h; repeated every 3 weeks.
1.4 Research Methods
A retrospective analysis. The main study endpoints efficiency and adverse reactions. The secondary endpoint of the study is progression-free survival time, time to progression, overall survival time. Determine the efficacy of using RECIST criteria, adverse reactions NCI CTC V3.0 standard. Progression-free survival time, time to disease progression and overall survival time were defined PCF regimen began on the first day to the recurrence and metastasis, disease progression or death interval.
1.5 statistical methods
SPSS 15.0 statistical software.
2.1 treatment situation
2.1.1 treatment of 35 patients with a total of 127 cycle the PCF regimen, 1 to 8 cycles, an average of 3.6 cycles, with a median three cycles.
2.1.2 dose intensity of 127 cycles of chemotherapy, the average dose intensity of paclitaxel 90% (95% CI, 87% ~ 92%),, cisplatin 108% (95% CI105% 110%), fluorouracil 86% (95% CI, 83% to 90%). Chemotherapy interval: 63% at intervals of 3 to 4 weeks, 30% at intervals of 4 to 5 weeks, 7% for more than five weeks apart.
2.2.1 adjuvant treatment of 35 cases, 15 cases of locally advanced gastric cancer patients (Ⅲ or Ⅳ) postoperative the PCF program of adjuvant chemotherapy. 10 cases of stage Ⅲ a, Ⅲ b of two cases, Ⅳ stage 3 patients. Followed up for 5 to 33 months, with a median followed up for 13.5 months. Seven cases (47%) had disease progression, 6 patients (40%) had died. The median progression-free survival time (PFS) 11.0 months, and median overall survival (OS) 18.6 months. 1-year survival rate was 83.6%, the 2-year survival rate was 39.0%. The survival curves shown in Figure 1.
2.2.2 rescue treatment of 20 patients with distant metastases in patients with gastric cancer, 18 cases of first-line treatment, the two cases for the second-line treatment after 3 cycles assessment, 15 patients evaluable. Complete remission (CR) 0 cases of partial remission (PR) 3 (20%), disease stability (SD) and 9 patients (60%), disease progress (PD), 3 patients (20%). Followed up for 2.8 to 34.4 months, with a median followed up for 8.0 months. 14 cases (70%) had died. The median time to progression (TTP) was 7.0 months, 9.0 months, and median overall survival time (OS). The survival curves shown in Figure 2.
The 2.3.1 35 cases in 6 cases (8.6%) can not tolerate the adverse reactions and discontinue chemotherapy.
2.3.2 Adverse reactions no chemotherapy-related deaths. Of 127 cycles of chemotherapy, major adverse hematologic toxicity including neutropenia incidence of 49.6%, anemia 48%; most common non-hematologic toxicity, gastrointestinal reactions, the incidence of nausea was 59%, vomiting 31.5%, followed by weakness 21.3%, diarrhea 16.5%, peripheral nerve sensory dysfunction 15.7%, and another higher proportion of elevated liver enzymes (14.2%). 3/4 adverse reactions, mainly nausea (18.1%), neutropenia (9.4%) and fatigue (7.9%). 9.5% of patients with neutropenia fever. Specific adverse reactions are shown in Table 1. Table 1 adverse reaction
Systemic chemotherapy is an important treatment for advanced gastric cancer. Some randomized studies have shown that, for advanced gastric cancer in combination with chemotherapy and best supportive care compared can prolong the survival time of 3 to 9 months, and improve the patient’s quality of life . However, due to the relatively small number of large-scale clinical studies, the current lack of a generally accepted standard chemotherapy.
In the 1990s, epirubicin, cisplatin combined with fluorouracil ECF program has been used as the standard program for the treatment of gastric cancer in Europe. Compared with FAMTX , the ECF regimen with high efficiency (45%: 21%), median progression-free survival time (7.4 months: 3.4 months), and median overall survival time (8.9 months: 5.7 months).
With the advent of taxane, taxane plus cisplatin, fluorouracil become a new hotspot for gastric cancer treatment. Paclitaxel for cell cycle-specific drugs, by polymerizing microtubules play the role of anti-mitotic, highly resistant to gastric cancer cell activity and could upregulate the the TP enzyme, enhanced 5 Fu role; cisplatin (DDP) is a broad-spectrum anticancer destruction of the structure and function of DNA, in addition to their own anti-tumor effect, also from the 5 Fu biochemical modulation; 5 Fu fluorouracil its metabolites phosphate deoxynucleotide reduced tetrahydrofolate and thymidine nuclear The nucleotide binding triplicate fit, to impede tumor cells DNA synthesis. Pharmacologically, the three-drug combination has a synergistic synergy.
Reasonable dosage and usage, different researchers in different attempts. Consider gastric cancer patients with chemotherapy tolerated relatively poor, and the program for the three-drug combination, and therefore paclitaxel appropriate reduction to 150mg/m2 day 1; discovered in recent years of high and low dose DDP and 5 Fu treating advanced gastric cancer, that no significant differences in , we use low-dose cisplatin to reduce adverse reactions in order to ensure the efficacy of the premise; 5 Fu continued infusion more effective than intravenous injection has been confirmed in colorectal cancer, therefore, We also learn from the treatment of gastric cancer.
In this paper, 20 cases of metastatic gastric cancer receive the PCF chemotherapy. CR cases after 3 cycles PR20% SD60% of, PD20%; median TTP was 7.0 months, and median OS was 9.0 months. The result is lower than reported in the literature. A review of research literature, Kim et al. , into the group of 41 patients with advanced gastric cancer, PCF rescue chemotherapy, CR10%, PR41 percent respectively; median TTP17 weeks and OS26 weeks, with a median. The study by Kollmannsberger people , into the group of 45 patients with locally advanced or metastatic gastric cancer, accepts PCF chemotherapy, CR11% PR40% SD20 is% PD29%; the median TTP9 months, with a median OS14 month. Honecker et al , into the group of 29 patients with previously untreated advanced gastric PCF program, CR14 PR34%, SD24% PD24%; TTP8, OS11. The current literature on the the PCF program of study report, study less number of cases, the lack of a large-scale randomized controlled study; therefore, can not truly reflect the the PCF program’s efficacy. Moreover, the three literature although the effective rate of about 50%, but the TTP, OS difference of many TTP3.9 to September, OS 6 to 14 months. Analyze the differences of the results of this study and the literature, considering (1) inclusion criteria: 20 cases in this article are the M1 Ⅳ patients and literature into the group of patients with inoperable locally advanced M0 patients resection. (2) the dose of chemotherapy drugs are used differently. (3) study the number of cases are less prone to bias. In this study, although the efficiency is slightly lower, but consistent clinical benefit rates with literature, up to 80%. The PCF program really efficient and is superior to other programs still need to verify.
Three meta-analysis confirmed the advantages of adjuvant therapy compared with surgery alone for locally advanced gastric cancer after adjuvant therapy, one meta-analysis , including 13 randomized trials, contrast Western countries adjuvant chemotherapy and surgery alone , adjuvant chemotherapy bring survival benefits (death OR0.80) to. Subgroup analysis showed that lymph node-positive patients account for at least 2/3 of the trials, adjuvant chemotherapy benefit more. Adjuvant chemotherapy for stage Ⅱ ~ Ⅲ patients has become routine. But also a lack of standard adjuvant chemotherapy programs. We retrospectively analyzed 15 patients with locally advanced (Phase Ⅲ or Ⅳ M0) gastric cancer patients received postoperative the PCF program of the efficacy of adjuvant chemotherapy, the median progression-free survival time (PFS) to 11.0 months, and median overall survival (OS) 18.6 months 1-year survival rate was 83.6%, the 2-year survival rate was 39.0%. Postoperative gastric cancer survival statistics, published 2000 review article , Ⅲ a patients with a total of 7481 cases, 1-year survival rate was 65%, 2-year survival rate was 39%. Compared with previous postoperative adjuvant therapy program, the PCF program 1-year survival rate has increased, but similar to the 2-year survival rate. Literature adjuvant chemotherapy regimen containing paclitaxel, less information. Japan is to carry out an advanced gastric cancer postoperative paclitaxel sequential S 1 adjuvant chemotherapy in clinical trials, the results have not been reported .
The program is mainly grade 3/4 adverse reactions are nausea (18.1%), neutropenia (9.4%) and fatigue (7.9%); 9.5% of patients with febrile neutropenia, but the anti-infection treatment ease soon. Compared with the ECF program, PCF programs toxicity is relatively low, ECF program  in the 3/4 neutropenia reduce the incidence of higher 36%, nausea / vomiting similar incidence of infection as high as 40%, which 3/4% 8%; However, fatigue has not been reported.
In short, we design improved PCF program adverse reactions can be accepted, no treatment-related deaths. Use the program to close monitoring of changes in blood cell counts, pay attention to the prevention of the use of granulocyte colony-stimulating factor; and strengthen antiemetic and supportive care. For the the PCF program’s efficacy, the needs of large-scale clinical trials further verification.