Gastric cancer is one of the common malignant tumors in China, and its death rate ranks the first among malignant tumor deaths [1]. Chemotherapy is one of the important treatment methods for progressive gastric cancer. Neoadjuvant chemotherapy refers to the application of systemic chemotherapy before the main treatment (surgery or radiotherapy). Its purpose is to shrink the tumor, increase the radical resection rate of surgery, improve the treatment effect, observe the sensitivity of chemotherapy drugs, and provide a reference basis for postoperative chemotherapy. There is no standard chemotherapy regimen in China so far. In this study, we observed the efficiency of mFOLFOX-6 neoadjuvant chemotherapy regimen, adverse effects of chemotherapeutic drugs and the effect on the risk of surgery and postoperative recurrence and metastasis rate, and survival rate. Zhang Bin, Department of General Surgery, Henan Cancer Hospital
1 Data and methods
1.1 General data 40 patients in this group, 23 males and 17 females; aged 38-68 years; mean age of observation group 61.1±10.7 years; mean age of control group 58.3±8.5 years; were patients treated in our hospital from January 2007 to January 2008, all were confirmed as gastric adenocarcinoma by pathological examination before surgery, no other treatment was performed, and were cT3-4N0- by CT examination. 3M0 patients, without severe cardiopulmonary disease and with KPS score ≥95. The patients were divided into two groups according to the treatment plan: the control group (20 patients) was treated with surgery alone, and the observation group (20 patients) was treated with 2-3 cycles of neoadjuvant chemotherapy before surgery, followed by surgery 2-4 weeks later. In the control group, there were 4 cases of pTNM stage IIIb, 10 cases of stage IIIa and 6 cases of stage II; in the observation group (18 cases), there were 2 cases of pTNM stage IIIb, 8 cases of stage IIIa and 7 cases of stage II, and 1 case of complete pathological remission; after surgery, both groups received adjuvant chemotherapy for 3-4 months.
1.2 Treatment Neoadjuvant chemotherapy was administered with mFOLFOX-6 regimen (oxaliplatin 85 mg/m2,ivgtt, day 1; calcium folinic acid 400 mg/m2 , ivgtt, day 1, 5-FU 400 mg/m2 , iv,5-FU 2400 mg/m2 ,46h, continuous iv, repeated once in 14d). Anti-allergic and ondansetron antiemetic treatment and hepatoprotective adjuvant therapy were routinely given before chemotherapy, and 2-3 cycles were completed to observe the efficacy. The surgical method was D2 or D3 resection.
1.3 Determination of efficacy and observation indexes The size of lesions was recorded in detail before chemotherapy, and CT examination was repeated after 2-3 cycles of chemotherapy, and the efficacy was determined by referring to the WHO recommended objective indexes for evaluating solid tumors (1981), which were classified as complete remission, partial remission, no change and progression; and adverse reactions were also observed and judged according to the WHO criteria for the manifestation and classification of acute and subacute toxicity of anticancer drugs. The risk of surgery in the two groups was observed: the incidence of postoperative SIRS, anastomotic fistula, incisional infection and postoperative complications (lymphatic fistula, intestinal obstruction), and the recurrence and metastasis rates and survival rates at 1, 2 and 3 years after surgery; SIRS (systemic inflammatory response syndrome, SIRS) was judged by the following criteria (1) body temperature > 38.0 ℃; (2) heart rate > 90 times/min; (3) respiration > 20 times/min; (4) white blood cell count > 12.0×109/L.
1.4 Statistical treatment SPSS 13.0 software was used for statistical analysis, and the measurement data were expressed as mean ± standard deviation (x ± s). The t-test was used, and the x2 test was used for the count data, and P < 0.05 was considered a statistically significant difference.
2 Results
2.1 General The patients in the observation group tolerated chemotherapy well, and the adverse reactions of chemotherapy (see Table 1) were mainly gastrointestinal reactions, bone marrow suppression and peripheral neurotoxicity, and no life-threatening adverse reactions occurred; 2 cases progressed without surgical treatment, and the remaining 18 cases had partial remission in 11 cases (1 case had complete remission of pathology, and no cancer cells were seen in postoperative pathology) and 7 cases were stable; the total effective rate was 55.0% (11/20). Among them, 1 case died of abdominal recurrence 3 months after radical surgery; 1 case died of liver metastasis 3 months after surgery and 6 months after surgery, 1 case in the control group died 2 months after surgery due to anastomotic fistula, 1 case died of abdominal recurrence 4 months after surgery and 7 months after surgery.
Table 1 Grading of adverse reactions to chemotherapy Example
Adverse reaction
0 degree
Degree Ⅰ
Ⅱ degree
Degree III
Degree IV
Blood system
Hemoglobin drop
White Blood Cell Decline
Decreased platelets
Digestive system
Stomatitis
Decreased liver function
Nausea and vomiting
Diarrhea
Decreased kidney function
Nervous system
Peripheral nerves
15
4
16
20
16
4
18
19
8
5
14
4
0
4
14
2
1
10
0
2
0
0
0
2
0
0
2
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
2.2 Observation index results There was no statistically significant difference in the comparison of age, gender between the two groups; there was no statistically significant difference in the comparison of postoperative SIRS incidence, anastomotic fistula situation and incisional infection and postoperative complications between the two groups (P > 0.05); there was a statistically significant difference in the comparison of intraoperative bleeding (<0.05). See Tables 2-3.
Table 2 Results of count data of 2 groups Example
Item
Observation group (n=18 cases)
Control group (n=20 cases)
P
SIRS
4 d postoperatively
14/18
15/20
0.841
6 d postoperatively
2/18
2/20
0.911
Anastomotic fistula
0/18
1/20
1.000
Incisional infection
0/18
0/20
–
Postoperative complications (lymphatic fistula, intestinal obstruction)
2/18
3/20
1.000
Table 3 Results of measurement data in 2 groups (±S)
Item
Observation group
Control group
P
Age
61.1±10.7
58.3±8.5
＞0.05
Intraoperative bleeding/mL
768.00±440.74
303.67±110.11
<0.05
Blood transfusion volume (red blood cells u)
3.41±2.14
2.32±3.44
＞0.05
Blood transfusion volume (plasma ml)
238.00±325.76
98.23±145.36
＞0.05
2.3 The recurrence and metastasis rates in the observation group at 1, 2 and 3 years were 22.2%; 50%; 50%; the recurrence and metastasis rates in the control group at 1, 2 and 3 years were 25%; 60%; 65%; the differences were not statistically significant when comparing the recurrence and metastasis rates in the two groups at 1, 2 and 3 years after surgery are shown in Table 4
Table 4 Comparison of recurrence and metastasis rates
Item
Observation group (n=18 cases)
Control group (n=20 cases)
P
1 year
4/18
5/20
0.841
2 years
9/18
12/20
0.536
3 years
9/18
13/20
0.350
2.4 The 1, 2, and 3-year survival rates in the observation group were 88.9%; 61.1%; 44.4%; the 1, 2, and 3-year recurrence and metastasis rates in the control group were 90%; 60%; 30%; the differences were not statistically significant when comparing the 1-year, 2-year, and 3-year postoperative survival rates between the two groups; see Table 5
Table 5 Comparison of survival rates
Item
Observation group (n=18 cases)
Control group (n=20 cases)
P
1 year
16/18
18/20
0.911
2 years
11/18
12/20
0.944
3 years
8/18
6/20
0.357
3 DISCUSSION
At present, the treatment of gastric cancer is still a comprehensive treatment mainly based on surgery. Neoadjuvant chemotherapy has become a research hotspot in recent years, and has become a hope to improve the efficacy of treatment for progressive gastric cancer due to the continuous emergence of new chemotherapeutic drugs [2, 6-7]. In China, Jin Mao-Lin [4] reported that the combination of oxaliplatin, fluorouracil, and calcium folinic acid had an efficiency of 42.5% for progressive gastric cancer, and Oh SY [5] reported that the efficiency of neoadjuvant chemotherapy for progressive gastric cancer with m-FOLFOX-4 regimen was about 50%. And the long-term efficacy needs to be further observed. ECF (epi-amycin + cisplatin + 5-fluorouracil) neoadjuvant chemotherapy regimens are advocated in Europe and the United States, and S-1-based chemotherapy regimens are advocated in Japan.
Clinical studies have shown that oxaliplatin has a significant inhibitory effect on a variety of tumors [5] and is not nephrotoxic, with no cross-resistance to tumors already tolerated by cisplatin. Recent European phase III clinical studies [10-11] have shown that oxaliplatin-containing chemotherapy has a better safety profile than cisplatin-based regimens; oxaliplatin can replace cisplatin in the treatment of advanced gastric cancer; therefore, the mFOLFOX-6 regimen was chosen for this study to achieve maximum efficiency and minimal adverse effects. In this study, we observed 20 cases of progressive gastric cancer, and the efficiency was 55.5 % when the CT was repeated 1 week after chemotherapy, and one case of postoperative pathology was in complete remission, which indicates that this regimen is effective for gastric cancer chemotherapy, and the efficiency is higher and the adverse effects of chemotherapy can be controlled without serious adverse effects compared with similar chemotherapy regimens (ECF, EOF, ECX) [10-11].
Neoadjuvant chemotherapy is a complement to, but not a substitute for, surgical treatment. In this study, the interval between chemotherapy and surgery was 2-3 weeks, and its adverse reactions such as myelosuppression caused by chemotherapy basically disappeared or stabilized. The lymph node metastasis of gastric cancer is an important factor affecting prognosis, and radical surgery for gastric cancer based on thorough clearance of the perigastric lymph nodes has made great progress in the surgical treatment of gastric cancer in Japan by detailed staging and grouping of perigastric lymph nodes [12]. In this study, D2 or D3 resection was selected as the surgical modality, and the results showed that there were no statistically significant differences in the incidence of postoperative SIRS, anastomotic fistula situation and incisional infection, and intraoperative blood transfusion between the two groups, suggesting that mFOLFOX-6 neoadjuvant chemotherapy regimen does not increase the surgical risk of patients, has high safety of perioperative application, and the adverse effects of chemotherapy can be controlled. In the observation group, the anatomy around the lesion was relatively clear and there was no obvious tissue edema, but there was more intraoperative exudation, which might be related to the tissue change after chemotherapy or to the short interval between chemotherapy and surgery. There was no statistically significant recurrence and metastasis rate at 1, 2 and 3 years after surgery, but there was a decreasing trend of recurrence and metastasis rate at 2 and 3 years, and there was no significant difference in survival rate at 1, 2 and 3 years after surgery, but there was a trend of increasing productivity at 3 years. Possibly related to the small number of cases in this group of patients.
Therefore, the mFOLFOX-6 regimen is feasible and safe for neoadjuvant chemotherapy in progressive gastric cancer without increasing the risk of surgery, and the 3-year survival rate of patients tended to increase, which is worthy of further application and study. However, the number of cases in this study is small, the observation time is still short, and the long-term effects are yet to be studied in further expanded samples.