Published online Sep 16, 2023. doi: 10.12998/wjcc.v11.i26.6083
Peer-review started: June 20, 2023
First decision: July 7, 2023
Revised: July 12, 2023
Accepted: August 11, 2023
Article in press: August 11, 2023
Published online: September 16, 2023
The incidence and mortality rates of gastric cancer in China are the second-highest in the world, and most patients with gastric cancer lose their chance of surgery by the time of their diagnosis.
To explore the predictive potential of serum basic fibroblast growth factor and interleukin-1β levels for the effect of first-line chemotherapy in patients with advanced gastric cancer.
From the gastric cancer patients admitted to our hospital from May 2019 to April 2023, 84 patients were selected and randomly and equally assigned to the experimental or control group. The FLOT group received the FLOT chemotherapy regimen (composed of oxaliplatin + calcium folinate + fluorouracil + paclitaxel), while the SOX group received the SOX chemotherapy regimen (composed of oxaliplatin + tiga capsules). The clinical efficacy, tumor marker levels, adverse reactions, and survival rates of the two groups were compared 7 days after the end of the relevant treatments.
The target effective rate of the FLOT group was 54.76%, which was much higher than that of the SOX group (33.33%; P < 0.05). After treatment, both the groups demonstrated lower levels of cancer antigen (CEA), carbohydrate antigen 199 (CA199), and peptide tissue antigen (TPS). For several patients before treatment (P < 0.05). Third and fourth grades. In terms of adverse reactions, the level of white blood cells in both the groups was lower. Moreover, the incidence of hand-foot skin reactions in these two study groups was lower (P < 0.05), while those of peripheral neuritis, vomiting, diarrhea, and abnormal liver function were significant (P < 0.05). No statistically significant difference was noted between the two groups (P < 0.05). The 1-year survival rate was higher in the FLOT group (P < 0.05).
The FLOT regimen was effective in reducing the serum CEA, CA199, and TPS levels as well as in improving the 1-year survival rate of patients with good tolerability, making it worthy of clinical promotion and application.
Core Tip: The prognosis of HER2-positive gastric cancer patients is generally worse; hence, there is an urgent need to explore new and effective treatments. Gastric cancer is a common malignant tumor disease in the digestive system. Cumulative data suggests that the incidence rate of gastric cancer ranks second among all malignant tumors, and the mortality rate ranks third. Furthermore, there is a rising trend in the incidence rate, which poses a serious threat to the physical and mental health of the population. The rapid development of modern medical technology has promoted the emergence of targeted therapy in clinical practice. However, due to the heterogeneous and complex nature of gastric cancer progression, its application is limited and the progress is slow.
- Citation: Zheng L, Gan LH, Yao L, Li B, Huang YQ, Zhang FB, Kuang MQ, Fang N. Serum basic fibroblast growth factor and interleukin-1β predict the effect of first-line chemotherapy in patients with advanced gastric cancer. World J Clin Cases 2023; 11(26): 6083-6090
- URL: https://www.wjgnet.com/2307-8960/full/v11/i26/6083.htm
- DOI: https://dx.doi.org/10.12998/wjcc.v11.i26.6083
Gastric cancer is a significant health concern in China, with the second-highest incidence and mortality rates worldwide; moreover, many patients are unable to undergo surgery at the time of diagnosis[1-5]. Chemotherapy is the primary treatment for advanced gastric cancer, but its efficacy is limited, which necessitates the exploration of new and effective therapies[5-10]. HER2, a member of the human epidermal growth factor receptor family, plays a crucial role as a tyrosine kinase receptor in regulating cell differentiation and proliferation, and its positivity is associated with the development, progression, and prognosis of gastric cancer[11-16]. Patients with HER2-positive gastric cancer generally have a poorer prognosis, highlighting the need for novel treatment approaches. In recent years, molecularly targeted therapies based on the understanding of tumor biology have demonstrated great promise, benefiting patients with advanced gastric cancer. Capecitabine + cisplatin has demonstrated efficacy in advanced gastric cancer; however, the role of trastuzumab, a HER2-targeted drug, remains underexplored[17,18]. This study aims to investigate the effectiveness of trastuzumab in combination with cisplatin for the treatment of HER2-positive gastric cancer by examining 86 patients with gastric cancer admitted to two hospitals.
Inclusion criteria: (1) Confirmed gastric cancer via gastroscopy and pathological biopsy; (2) HER2 positivity (++++) determined by the immunohistochemistry of the tumor tissues; (3) distant metastasis confirmed by computed tomography or magnetic resonance imaging without indication for surgery; (4) Eastern Cooperative Oncology Group score of 0-2; (5) good physiological function (white blood cell count ≥ 3 × 103/mm3, platelet count ≥ 105/mm3, and hemoglobin ≥ 9.0 g/dL); (6) Karnofsky performance status score ≥ 60; and (7) signed informed consent form.
Exclusion criteria: (1) The presence of large pleural/pericardial effusion requiring drainage; (2) active growth of malignant brain metastases; (3) allergy to chemotherapy drugs; (4) serum carcinoembryonic antigen (CEA) level < 3.4 ng/mL; (5) pregnancy or lactation; and (6) presence of other serious diseases.
The patients were assigned to the chemotherapy drug combination regimen group and the first-line chemotherapy regimen group. There were no shared data between the statistical groups (P > 0.50), ensuring comparability.
Patients in the chemotherapy drug combination and first-line chemotherapy regimen groups were orally administered with 0.75 mg of dexamethasone (Guangdong Huainan Pharmaceutical Group Co., Ltd., approval number: Guodianzhi H44024469, specification: 0.75 mg × 100 tablets) prior to initiating chemotherapy to prevent allergy. In addition, they were administered 4 mg of ondansetron (Qilu Pharmaceutical Co: Ltd., approval No.: Qilu Pharmaceutical Co., Ltd., approval number: H10970062, specification: 4 mg × 12 tablets) and 5 mg of metoclopramide (Shaanxi Yunpeng Pharmaceutical Co., Ltd., approval number: H14020782, specification: 5 mg × 100 tablets) to prevent vomiting. During chemotherapy, the patients were advised to keep warm and avoid cold exposure. Nutritional support was provided to prevent malnutrition, and routine blood, urine, and electrocardiogram tests were conducted weekly to monitor the patient’s health status.
The patients in the first-line chemotherapy regimen group were administered tegeo capsules and oxaliplatin as follows: Intravenous injection (130 mg/m2 once) of oxaliplatin (Jiangsu Hengrui Pharmaceutical Co., Ltd., approval number: Guodianzhizhi H20000337, specification: 50 mg), and oral administration of tegeo capsules (Qilu Pharmaceutical Co., Ltd., approval number: Guodianzhizhi H20100151, specification: 25 mg × 28 capsules) twice a day for 14 d and then stopped for 7 d. One cycle comprised 21 d, and two cycles were continuously administered.
The patients in the chemotherapy drug combination group were administered a combination of drugs (oxaliplatin + calcium folinic acid + fluorouracil + paclitaxel) as follows: Paclitaxel injection (Guangdong Xinghao Pharmaceutical Co., Ltd., approval number: H20000337, specification: 50 mg) via an intravenous drip at 85 mg/m2 for 1 d; calcium folinic acid injection (Guangdong Lingnan Pharmaceutical Co., Ltd., approval number: H20057260, specification: 50 mg) via an intravenous drip at 200 mg/m2 for 1 d; and fluorouracil (Xi'an Haixin Pharmaceutical Co., Ltd., approval number: Guodianzhi H20050511, specification: 0.25 g) was intravenously administered continuously via a micropump for 24 h at 2 000 mg/m2 for 1 d and repeated once in 14 d. The treatment was continued for two cycles, with one cycle comprising 14 d.
Clinical efficacy: The efficacy of both the groups 7 days after the completion of relevant treatment was evaluated. The main categories were complete remission (CR), partial remission (PR), stability (SD), and progression (PD). CR was considered when the tumor lesion had disappeared, clinical symptoms had disappeared, and the maintenance time was > 4 wk. PR was considered when the sum of the longest diameter of the lesion decreased by ≥ 30%, with a maintenance time of ≥ 4 wk. SD was considered when the disease was between PR and PD. PD was considered when the diameter was the longest and the target lesion had increased by ≥ 20%. The objective response rate (ORR) was calculated as follows: (CR + PR) number of cases/total number of cases × 100%.
Tumor markers: Five milliliters of fasting venous blood were collected from each patient in the FLOT and SOX groups within 1 wk before and in the morning after the treatment; the samples were then centrifuged and separated to determine CEA and glycoantigen 199 (CA199) concentrations and the serum tissue peptide-specific antigen (TPS) levels via indirect enzyme-linked immunosorbent assay.
Adverse reactions: Based on the anticancer drug toxicity reaction grading standards of the World Health Organization, skin reactions on the hands and feet, peripheral neuritis, vomiting, diarrhea, abnormal liver function, and leukopenia were graded as grade 0 (no reaction), grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (life-threatening). Incidence was calculated as follows: Number of adverse reaction cases/total cases × 100%.
Survival rate: The survival rates of the two groups at 6 mo and 1 year were recorded at 1-year follow-up.
The data of the two groups were initially collated in an Excel sheet and then imported into SPSS 20.0 software for analysis. Statistical data (efficacy, adverse effects, and survival rates) were expressed as a rate (%) using the χ2 test. Measurement data (tumor marker level, age, and weight) were expressed as (mean ± SD) using the t-test for independent samples between groups and the paired t-test within groups. P < 0.05 indicated that the difference is statistically significant.
The FLOT group comprised 29 men and 13 women aged 78 and 43 years (average age 55.46 ± 10.67 years), respectively, and weighing 47.5-77.6 kg (average 62.31 ± 13.07 kg). The SOX group comprised 30 men and 12 women aged 75 and 41 years (average 54.98 ± 11.39 years), respectively, and weighing 46.2-76.4 kg (average 63.23 ±12.76 kg). The overall data of the two groups were not statistically significant (P > 0.05) and were comparable.
The ORR of the FLOT group was 54.76%. The differences were statistically significant (χ2 = 3.913, P < 0.05), as presented in Table 1.
| Group | CR, n (%) | PR, n (%) | SD, n (%) | PD, n (%) | ORR (%) |
| FLOT group (n = 42) | 0 (0.00) | 23 (54.76) | 14 (33.33) | 5 (11.90) | 54.76 |
| SOX group (n = 42) | 0 (0.00) | 14 (33.33) | 15 (35.71) | 13 (30.95) | 33.33 |
No statistically significant difference was observed in the CEA, CA199, and TPS levels between the two groups before treatment (P > 0.05). However, after treatment, the CEA, CA199, and TPS levels in both the patient groups were significantly lower than those before treatment. These levels were lower in the FLOT group than in the SOX group, with statistical significance (P < 0.05); on the other hand, the FLOT group was higher than the SOX group (P < 0.05), as presented in Table 2.
| Group | CEA (ng/mL) | CA199 (U/mL) | TPS (U/L) | |||
| Before treatment | After treatment | Before treatment | After treatment | Before treatment | After treatment | |
| FLOT group (n = 42) | 40.16 ± 8.84 | 33.79 ± 5.76a | 45.76 ± 10.14 | 24.07 ± 4.67a | 160.27 ± 31.69 | 47.63 ± 5.09a |
| SOX group (n = 42) | 39.41 ± 8.23 | 37.31 ± 7.64a | 46.51 ± 10.63 | 29.74 ± 6.52a | 162.34 ± 27.32 | 62.31 ± 7.62a |
| t-value | 0.402 | 2.384 | 0.331 | 4.582 | 0.321 | 10.382 |
| P value | > 0.05 | < 0.05 | > 0.05 | < 0.05 | > 0.05 | < 0.05 |
White blood cell disease was more common in the FLOT group than in the SOX group, with lower hand-foot skin reactions being more common in the FLOT group than in the SOX group (P < 0.05). However, there was no statistically significant difference between the two groups in terms of peripheral neuritis, vomiting, diarrhea, and liver dysfunction (P > 0.05), as presented in Table 3.
| Group | Level | Skin reactions on hands and feet | Peripheral neuritis | Vomiting | Diarrhea | Abnormal liver function | Leukopenia |
| FLOT group (n = 42) | Level 0 to 2; Level 3 & 4 | 41 (97.62); 1 (2.38) | 41 (97.62); 1 (2.38) | 38 (90.48); 4 (9.52) | 39 (92.86); 3 (7.14) | 40 (95.24); 2 (4.76) | 25 (59.52); 17 (40.48) |
| SOX group (n = 42) | Level 0 to 2; Level 3 & 4 | 34 (80.95); 8 (19.05)a | 42 (100.00); 0 (0.00) | 40 (95.24); 2 (4.76) | 40 (95.24); 2 (4.76) | 41 (97.62); 1 (2.38) | 35 (83.33); 7 (16.67)a |
Cox regression analysis revealed that basic fibroblast growth factor (bFGF, HR = 2917, 95% confidence interval: 1066-7978, P = 0.037) and IL-8 (HR = 3191, 95% confidence interval: 1148-8870, P = 1.026) acted as independent risk factors for adverse OS. In addition, high FBGF (P = 0.013) and high IL-8 (P = 1.027) acted as independent risk factors for shorter PFS (Table 4).
| Related factors | HR | 95%CI | Standard error | P value |
| bFGF (pg/mL) | 2.917 | 1.066-7.978 | 0.513 | 0.037 |
| IL-1β (pg/mL) | 1.155 | 1.062-3.124 | 0.563 | 0.078 |
| TNF-α (μg/L) | 1.037 | 0.669-2.140 | 0.436 | 0.092 |
| Single organ transfer | 0.073 | 0.019-1.320 | 0.721 | 0.541 |
| Multi-organ metastases | 1.024 | 0.725-1.925 | 0.547 | 0.354 |
| Tumor location | 1.093 | 0.763-1.724 | 0.852 | 0.320 |
| Tissue differentiation | 1.115 | 0.975-1.520 | 0.973 | 0.163 |
The difference in the 6-mo survival rate of the two groups was not statistically significant (P > 0.05). However, the 1-year survival rate of the FLOT group was higher than that of the SOX group (P < 0.05) (Table 4).
Gastric cancer is a common malignant disease of the gastrointestinal system[19,20]. It has the second-highest incidence rate and the third-highest mortality rate among all malignant tumors, showing an upward trend each year; as a result, this cancer type seriously threatens the physical and mental health of the country[22-27]. Rapid advances in modern medical technology have led to the emergence of targeted drugs in clinical settings; however, owing to the heterogeneity and complexity of cancer development, their applications are limited and the relevant progress remains slow[28]. Presently, systemic chemotherapy remains the main treatment strategy for advanced or recurrent metastatic gastric cancer. Optimizing the chemotherapy regimen is thus an important strategy for improving its effects.
SOX is the main first-line chemotherapy regimen for patients with advanced cancer, whereas oxaliplatin is a third-generation platinum-based anticancer drug. When patients orally receive tegafurin capsules, tegafurin is converted into fluorouracil in the body and used in combination with oxaliplatin to fully exert its antitumor effect[29-33]. Recently, chemotherapy regimens containing paclitaxel have achieved exciting results in clinical settings; however, they have shortcomings owing to their strong toxic side effects. Nevertheless, the streaming protocol has been optimized and improved based on the original DCF protocol. In this study, FLOT was used as the first-line treatment for advanced gastric cancer. We noted that the ORR of the FLOT group (54.76%) was significantly higher than that of the SOX group (33.33%).
Angiogenesis and inflammatory cytokine release are cancer-related markers. The early detection of appropriate therapeutic biomarkers can help formulate treatment strategies and improve patient survival[34-40]. Nevertheless, our study has some limitations. First, it was a single-center study and had a limited sample size; therefore, the sample size should be further expanded to confirm this finding. Second, this study only analyzed angiogenesis and inflammatory factors without analyzing markers for oxidative stress damage (such as 8-oxo dG), vascular maturation, and cell proliferation (such as Ki-67) in the tissue samples.
In summary, FLOT is an effective first-line chemotherapy regimen for advanced gastric cancer. It can decrease the serum CEA, CA199, and TPS levels and improve the 1-year survival rate of patients; furthermore, it has good tolerance. Therefore, it is worthy of clinical promotion and application.
The incidence and mortality rates of gastric cancer in China are the second-highest in the world, and most patients with gastric cancer lose their chance of surgery by the time of their diagnosis.
To explore the potential of serum basic fibroblast growth factor (bFGF) and interleukin-1β (IL-1β) levels in predicting the effect of first-line chemotherapy in patients with advanced gastric cancer. To evaluate the relationship between the serum levels of bFGF and IL-1β and the therapeutic response to first-line chemotherapy in patients with advanced gastric cancer in order to determine their value as predictive markers.
This prospective study on patients with advanced gastric cancer (as study subjects) was undertaken to provide a reference for the prognosis and anesthesia of clinical-related operations.
Randomized controlled method and double-blinded method. Prior to the initiation of chemotherapy, serum samples are collected from the participants for the determination of the levels of bFGF and IL-1β. Subsequently, the patients underwent first-line chemotherapy, and the treatment response was assessed at the end of the chemotherapy cycle.
Previous reports have suggested that capecitabine + cisplatin has a clear efficacy in advanced gastric cancer, albeit there is a lack of relevant studies on trastuzumab - a drug that targets HER2 tumor cells. The researchers analyzed the association between the serum levels of bFGF and IL-1β and the therapeutic response to first-line chemotherapy. The possible outcomes include poorer treatment response, such as smaller tumor shrinkage or faster disease progression, in patients with higher levels of bFGF and IL-1β after the first-line chemotherapy.
In this study, 86 gastric cancer patients admitted to two hospitals were examined to investigate the efficacy of trastuzumab in combination with cisplatin in the treatment of HER2-positive gastric cancer. Based on the research findings, we suggest that the serum levels of bFGF and IL-1β can serve as predictive markers for the therapeutic response to first-line chemotherapy in patients with advanced gastric cancer. The measurement of these biomarkers can provide additional information to clinicians, thereby assisting in decision-making and the development of personalized treatment plans.
Predictive role of serum bFGF and IL-1β in first-line chemotherapy for advanced gastric cancer.
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Gastroenterology and hepatology
Country/Territory of origin: China
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P-Reviewer: Cristescu R, South Korea; Shafabakhsh R, Iran S-Editor: Yan JP L-Editor: A P-Editor: Yu HG
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