Efficacy of cisplatin in combination with paclitaxel for oral cancer and its effect on cellular immunity

Purpose: To study the efficacy of cisplatin in combination with paclitaxel in the treatment of oral cancer and its effect on cellular immunity. Methods: A total of 100 patients with oral cancer, treated in the First Affiliated Hospital of Dalian Medical University from May 2018 to April 2020 were included and evenly allocated to study and control groups. The patients in the study group received cisplatin plus paclitaxel, while the patients in the control group received only cisplatin. The serum levels of T lymphocytes, interleukin (IL) -4, IL-2, and interferon gamma (IFN-γ) were determined. Results: After treatment, the study group showed significantly higher levels of CD3+, CD4+ and CD4/CD8, but a lower CD8+ level (26.17 ± 2.14 μL). than those before treatment (p < 0.05). The control group was associated with higher post-treatment CD3+, CD4+, CD8+, and CD4/CD8 levels and lower CD8+ levels versus patients in the study group (p < 0.05). The study group showed higher levels of IL-2 and INF-γ, (246.77 ± 13.68 and 1194.62 ± 123.15 pg/mL), respectively, but lower IL-4 levels (392.48 ± 13.25 pg/mL) after treatment than before treatment. Control group was associated with higher post-treatment IL-2 and INF-γ levels and lower IL-4 levels compared to patients in the study group (p < 0.05). Conclusion: Cisplatin and paclitaxel combination offers a viable treatment alternative for oral cancer, as it enhances patients’ immune function and disease prognosis, regulates inflammatory responses, and promotes patients’ recovery. Further investigations in larger population settings are, however, recommended.


INTRODUCTION
Oral cancer is a common malignancy [1], including lip cancer, tongue cancer, jaw cancer, gum cancer, buccal mucosa cancer, etc. [2]. According to epidemiological statistics, there are nearly 300,000 new cases each year in recent years, and the pathogenesis is mainly related to biological and environmental factors [3,4]. The clinical symptoms of oral cancer mostly include pain, leukoplakia, and chronic oral ulcers [5,6]. Presently, surgical resection, radiotherapy, and chemotherapy are the mainstay of treatment for oral cancer [7]. However, the treatment outcome is suboptimal, and patients are still associated with poor survival and high recurrence and metastasis rates [8].
Cisplatin is a broad-spectrum anti-tumor chemotherapeutic drug that has obtained promising results in treating solid tumors such as ovarian cancer, testicular cancer, and lung cancer [9]. It inhibits the synthesis of DNA and RNA in tumor cells to exert the anti-tumor function and plays a synergistic effect with 5-Fluorouracil (5-FU) [10]. Paclitaxel is a natural secondary metabolite obtained from Taxus chinensis and has good antitumor effects for breast cancer, ovarian cancer, and lung cancers [11]. In recent years, neoadjuvant chemotherapy with paclitaxel has achieved good clinical results [12,13]. This study was undertaken to investigate the efficacy of the combination of cisplatin and paclitaxel for oral cancer and its impact on cellular immunity.

Study population
A total of 100 patients with oral cancer treated in the First Affiliated Hospital of Dalian Medical University between May 2018 and April 2020 were selected and assigned to the observation and control groups. The study was approved by the ethic committee of First Affiliated Hospital of Dalian Medical University (approval no. 20180230). The study was conducted in line with the protocol of Helsinki Declaration [14]. All the patients consented to participate in the study.

Inclusion criteria
Patients with oral squamous cell carcinoma, without allergies to the drugs used in this treatment, and with consciousness that allows normal communication were included.

Exclusion criteria
Patients with systemic diseases such as diabetes and hypertension, with autoimmune disease and use of immunosuppressive drugs, and who revoked their consent were excluded.

Treatments
Patients in the observation group received 100 mg/m 2 of cisplatin and 150 mg/m 2 of paclitaxel through an intravenous infusion for 5 days, starting from the first day of treatment, and repeated 30 days after first treatment. Patients in the control group received only 100 mg/m 2 of cisplatin through an intravenous infusion 5 days starting on the first day of treatment, and repeated 30 days after first treatment. Approximately 2 mL of venous blood was collected from all participants for the determination of blood indices. All testing methods used were in line with the relevant laboratory diagnostic standards.

Treatment efficacy
If the symptoms and signs were significantly mitigated and the test indices were markedly improved after treatment, the treatment was considered markedly effective. After treatment, if the symptoms and signs were mitigated and the test indices were improved, the treatment was considered effective. If aggravations or no changes were observed in the symptoms and test indices after treatment, the treatment was considered ineffective.

Peripheral venous blood test
The blood samples were centrifuged, and the supernatant was collected for assays using the ELISA method. The determination of blood indices was performed as per the kit instructions.

T-lymphocyte measurement
Blood samples collected from each patient was divided into four portions of 100 μL in each group for assay. The first portion was added with FITClabeled CD3 antibody and PE-labeled CD56 antibody, the second portion was added with FITC-labeled CD4 antibody and PE-labeled CD8 monoclonal antibody, the third portion was added with FITC-labeled CD4 antibody and PE-labeled INF-γ antibody, and the fourth portion was added with FITC-labeled CD4 antibody and PE-labeled IL-2 antibody, with the dose of each antibody sample being 10 μL. The specimens were then incubated for 1 h, added with red blood cell lysate, allowed to react for 10 min, and then centrifuged for 5 min, followed by the collection of the supernatant for assays using flow cytometry.

Statistical analysis
All data analyses were performed with SPSS 22.0 software. The count data (n (%)) are analyzed using the chi-square test. The measurement data (mean ± SD) were analyzed using t-test. A p-value less than 0.05 was set as the cut-off for statistical significance.

Baseline characteristics of patients
In the study group, there were 35 males and 15 females, 34 cases of clinical stage III, and 16 cases of clinical stage IV, and the participants were aged 51.23 ± 5.18 years. In the control group, there were 36 males and 14 females, 33 cases of clinical stage III, and 17 cases of clinical stage IV, and the participants were aged 51.08 ± 5.37 years. The patient characteristics between the two groups were comparable (p > 0.05) ( Table 1).

Treatment effectiveness
After treatment, in the study group, there were 18 cases that were significantly effective, 25 cases were effective, and 7 cases were ineffective; while in the control group, there were 10 markedly effective cases, 20 cases were effective, and 20 cases were ineffective ( Table  2).

DISCUSSION
Oral cancer is clinically treated with surgical resection, supplemented with radiotherapy and chemotherapy [15], yet both have a high degree of recurrence and metastasis. Cisplatin is a clinical anticancer drug [16] with cell cycle nonspecificity. It inhibits the synthesis of DNA and RNA to exert anti-tumor effects. Research has reported that cisplatin is effective in various solid tumors such as ovarian cancer and prostate cancer, testicular cancer, lung cancer, nasopharyngeal cancer, esophageal cancer, malignant lymphoma, head and neck squamous cell carcinoma, thyroid cancer and osteosarcoma [10]. Paclitaxel is a common drug in neoadjuvant chemotherapy with good antitumor activity [17].
In the present study, patients in the study group showed treatment effectiveness of 95.56 %, indicating that the combination of cisplatin and paclitaxel are effective for oral cancer. Moreover, the study group showed higher levels of CD3+, CD4+, CD4/CD8 after treatment and a lower CD8+ level than those before treatment suggesting that cisplatin and paclitaxel improve patient immunity and promote the recovery of patients. The results were consistent with the previous studies [18,19]. Additionally, the study group showed higher levels of IL-2 and INF-γ and lower IL-4 levels after treatment than before treatment and the differences in the three indices between the two groups were also statistically significant, suggesting alleviated inflammatory responses in the patients and enhanced secretion of cytokines after the use of cisplatin and paclitaxel. This outcome is similar to the previous research results that reported that inflammatory factors in peripheral blood increased significantly, and the immune function of peripheral blood cells was improved, resulting in diminished tumor volume [20].

CONCLUSION
The combination of cisplatin and paclitaxel offers a viable treatment alternative for oral cancer, as it enhances patients' immune function and improves disease prognosis, regulates their inflammatory responses, and promotes their recovery. However, further studies in larger population groups are recommended.

Acknowledgements
None provided.

Funding
None provided.

Ethical approval
None provided.

Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.