Abstract
Objective: To explore the effect of nimotuzumab combined with Taxol + Cisplatin (TP) regimen induction chemotherapy and sequential concurrent chemoradiotherapy on the improvement of curative effect and prognosis of patients with locally advanced nasopharyngeal carcinoma. Method: A retrospective analysis was performed on 91 patients with locally advanced nasopharyngeal carcinoma who were admitted to our hospital from February 2017 to February 2019, of which 41 patients received TP induction chemotherapy were assigned to control group (CG), and the remaining 50 patients received nimotuzumab on the basis of control group were assigned to observation group (OG). Both groups of patients received cisplatin chemotherapy concurrently with intensity-modulated radiotherapy (IMRT). Comparisons were made between the two group in terms of clinical efficacy, serum markers squamous cell carcinoma-associated antigen (SCCAg), cytokeratin 19 fragment 21-1 (CYFRA21-1), adverse reactions, and 3-year survival of the patients. Results: Remission rate of cervical lymph nodes in OG was better than that in CG (P<0.05). After treatment, SCC-Ag and CYFRA21-1 decreased significantly in both groups, while indexes in OG were markedly lower compared to CG (P<0.05). During induction therapy and concurrent chemoradiotherapy, no notable difference was observed in short-term or long-term adverse reactions between the two groups (P>0.05). And Cox regression analysis found that clinical stage and treatment were independent factors affecting the prognosis of patients with disease-free survival (PFS). Conclusion: Nimotuzumab combined with TP regimen induction chemotherapy and sequential concurrent chemoradiotherapy can improve the curative effect of patients with locally advanced nasopharyngeal carcinoma.
Keywords: Nimotuzumab, TP regimen, chemoradiotherapy, locally advanced nasopharyngeal carcinoma, efficacy, prognosis
Introduction
Nasopharyngeal carcinoma (NPC) is a malignant tumor originating from the epithelium of the nasopharyngeal mucosa, which is sensitive to radiation and can be clinically cured by early radiotherapy alone [1]. In China, it mostly occurs in southern provinces, with Guangdong accounting for the highest incidence [2]. Studies have reported that the pathogenesis of NPC was related to genetics, EBV infection, environment, diet and other factors [3]. However, the pathogenesis of NPC still remains unclear. Due to the insidious nature of NPC and the lack of typical symptoms in its early stages, 70% of patients are locally advanced at the initial visit [4]. The 5-year survival rate of locally advanced NPC patients after radical treatment is only 50-60%, and the main factors attribute to treatment failure are local recurrence and distant metastasis [5].
At present, radiotherapy-based chemoradiotherapy combined with targeted and immune comprehensive therapy is an important treatment mode for locally advanced NPC, and induction chemotherapy can create better radiotherapy conditions and reduce the risk of metastasis [6]. However, on the basis of platinum-based concurrent chemoradiotherapy, 5-15% of NPC patients still experience local-regional recurrence, and 15-30% of NPC patients undergo distant metastasis [7,8]. Studies have found that [9] the main targets of intervention in NPC were epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR). In the study of Zhang et al. [10], it was found that EGFR was highly expressed in NPC patients, and there is evidence showing that EGFR overexpression was associated with radiotherapy resistance and poor prognosis of patient. With the continuous development of molecular targeted therapy technology, EGFR inhibitors led by nimotuzumab and cetuximab have entered clinical application in recent years [11]. By competitively binding with EGFR, it can block the downstream signal transduction pathway mediated by EGFR, thereby inhibiting tumor cell proliferation, inducing differentiation, promoting cell apoptosis, and inhibiting tumor angiogenesis [12]. Nimotuzumab is a novel humanized monoclonal antibody that can effectively improve the sensitivity of radiotherapy [13], which has become a hot spot in the treatment of locally advanced NPC in recent years due to its strong specificity and mild side effects [14]. There is, however, no report focused on the combination therapy of nimotuzumab and TP regimen.
To this end, this study aimed to analyze the effect of nimotuzumab combined with TP regimen induction chemotherapy and sequential concurrent chemoradiotherapy on the efficacy in locally advanced NPC patients, and to analyze the impact of this treatment regimen on the prognosis of patients, so as to provide guidance for clinical treatment plans.
Methods and materials
Clinical information
A retrospective analysis was performed on 91 patients with locally advanced nasopharyngeal carcinoma who were admitted to our hospital from February 2017 to February 2019, of which 41 patients received (TP) induction chemotherapy were as assigned to the control group (CG), and the remaining 50 patients received nimotuzumab on the basis of control group were assigned to the observation group (OG). Both groups of patients received cisplatin chemotherapy concurrently with intensity-modulated radiotherapy (IMRT). This study received approval from the medical ethics committee of our hospital, and all patients were informed about the study with informed consent signed. Ethical batch number: LL2020048.
Inclusion and exclusion criteria
Inclusion criteria
Patients in line with the 8th edition of AJCC NPC tumor staging criteria [15]; Patients with clinical stage of III-IVa; Patients with an age of 18-70 years; Patients with NPC confirmed by pathological examination with pathological type of undifferentiated non-keratinizing carcinoma, differentiated nonkeratinizing carcinoma, or keratinizing squamous cell carcinoma; Patients who had at least 1 cycle of standard platinum-based induction chemotherapy, with a performance status (PS) score of 0-1 before radiotherapy.
Exclusion criteria
Patients with other tumors; Patients with incommensurable clinical efficacy; Patients with incomplete clinical data; Patients with intolerance to drugs concerned; Patients who had been treated with EGFR receptor inhibitors and similar drugs before concurrent chemoradiotherapy; Pregnant women.
Treatment plan
Chemotherapy regimen
CG patients received TP regimen: docetaxel (Shanghai Chuangnuo Pharmaceutical Co., Ltd., H20113165) 75 mg/m2 and paclitaxel liposome (Jiangsu Osaikang Pharmaceutical Co., Ltd., H20083848) 135 mg/m2, intravenous infusion once every 3 weeks; Nedaplatin (Jiangsu Osaikang Pharmaceutical Co., Ltd., H20143132) 80 mg/m2 and cisplatin 75 mg/m2, intravenous infusion once every 3 weeks. OG patients were treated with nimotuzumab on the basis of CG: nimotuzumab injection 200 mg, intravenous drip, once a week. The rest of the program was the same as CG. 2-3 times after induction, cisplatin chemotherapy was conducted, with cisplatin 40 mg/m2 intravenous drip once a week in a total of 6 times, combined with concurrent intensity-modulated radiotherapy (IMRT).
Radiotherapy regimen
All patients in this study received IMRT treatment. Tumor extent was determined by magnetic resonance imaging (MRI), the target volume was delineated on enhanced CT for the design of treatment plan. Reverse intensity-modulated plan was designed and optimized using 6 MV X-ray intensity-modulated radiotherapy technology. The radiation dose was determined according to the size of the tumor: primary tumor (PGTVnx) 69.96 Gy-71.28 Gy/33 f, cervical lymph node (PGTVnd) 66 Gy/33 f, visible lesions + upper neck lymphatic drainage area (PTV1) 60.06 Gy/33 f, lower cervical lymphatic drainage area (PTV2) 50 Gy-52.8 Gy/33 f. Above therapy was conducted 5 times a week for 6-7 weeks. Organ-at-risk dose-limiting and planning assessments were performed at the request of the Radiotherapy Collaborative Group.
Tumor marker detection
Before and after receiving induction therapy, 5 ml of fasting venous blood was collected and centrifuged at 1500 rpm for 10 min to obtain serum for detection. The level of squamous cell carcinoma-associated antigen (SCC-Ag) was determined by enzyme-linked immunosorbent assay, and that of cytokeratin 19 fragment 21-1 (CYFRA21-1) was by electrochemiluminescence method. SCC-Ag kit was purchased from Shanghai Enzyme Link, ml058616, and CYFRA21-1 kit was from Shanghai Toujing Life Technology Co., Ltd., 18A002.
Adverse reaction statistics
The acute and late adverse reactions of radiotherapy were evaluated according to the RTOG acute and late radiation response scoring criteria. According to the common toxicity standard observation records of the National Cancer Center (NCI-CTC version 3.0), they were divided into grades 0-IV.
Clinical response evaluation criteria
Tumor regression was assessed by imaging (CT or MR) 1 month after the end of treatment. The treatment efficacy was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) [16]. Specific criteria are as follows: complete response (CR), disappearance of all target lesions, short diameter of all pathological lymph nodes was <10 mm for at least 4 weeks (at the time of overall response assessment, initially elevated tumor markers returned to normal). Partial response (PR), the total diameter of the target lesion decreased by at least 30% for at least 4 weeks; progression of disease (PD), the total diameter of the target lesion increased by at least 20%, or new lesions occurred; stable disease (SD), the reduction of target lesions did not reach the level of PR, and the extent of target lesion did not reach the level of PD but was in between. The total effective rate (RR) = (CR+PR) cases/total cases ×100%.
Observation indicators
Main outcome measures
The changes in serum SCC-Ag and CYFRA21-1 levels before and after treatment were observed. The primary lesions, posterior cervical lymph nodes, and overall treatment efficacy in patients after recent induction therapy were compared, as well as the overall curative effect after the whole course of treatment (the efficacy evaluation is the grade data. The CR, PR, PD and SD patients in each group are regarded as the whole, and the data are analyzed through the rank sum test, that is, the overall effective rate). The Kaplan-Meier (KM) survival curve was used to analyze the overall survival (OS) and disease-free survival (PFS) of the patients, and Cox regression was used to analyze the prognostic factors affecting PFS of patients.
Secondary outcome measures
The clinical data and incidence of adverse reactions of the two groups of patients were compared.
Statistical analysis
In this study, SPSS 20.0 software was used to analyze the collected data. Count data were expressed as n (%) and compared using x2 test. Rank data were assessed with Mann-Whitney test and expressed as Z. K-M survival curve was used to draw the overall survival of patients, which was analyzed by Log-rank test. Cox regression was used to analyze the independent prognostic factors of the patients. And p<0.05 was considered to be statistically different.
Results
Comparison of clinical data
Analysis suggested that there were no notable differences regarding gender, age, T stage, N stage, clinical stage, pathological type, induction treatment time between the two groups (P>0.05, Table 1).
Table 1.
Clinical data
| Factors | Control group (n=41) | Observation group (n=50) | P |
|---|---|---|---|
| Gender | 0.412 | ||
| Male | 28 | 38 | |
| Female | 13 | 12 | |
| Age | 0.216 | ||
| >60 years old | 25 | 24 | |
| ≤60 years old | 16 | 26 | |
| T Stage | 0.955 | ||
| T1 | 5 | 7 | |
| T2 | 6 | 6 | |
| T3 | 16 | 18 | |
| T4 | 14 | 19 | |
| N Stage | 0.185 | ||
| N1 | 5 | 13 | |
| N2 | 19 | 23 | |
| N3 | 17 | 14 | |
| Clinical Stage | 0.442 | ||
| Stage III | 23 | 24 | |
| Stage IVa | 18 | 26 | |
| Pathological Type | 0.810 | ||
| Nonkeratinizing Squamous Cell Carcinoma | 15 | 17 | |
| Undifferentiated Squamous Cell Carcinoma | 1 | 2 | |
| Poorly Differentiated Squamous Cell Carcinoma | 15 | 15 | |
| Other Differentiated Squamous Cell Carcinoma | 10 | 16 | |
| Induction Therapy Cycle | 0.206 | ||
| 2 cycles | 11 | 8 | |
| 3 cycles | 30 | 42 |
Changes of tumor markers before and after treatment
Serum levels of SCC-Ag and CYFRA21-1 after treatment were markedly lower than those before treatment in both groups of patients (P<0.05). Further comparison showed that the levels of those in CG after treatment were higher than those in OG (Figure 1, P<0.05).
Figure 1.
Changes of SCC-Ag and CYFRA21-1 levels in serum of patients before and after treatment. A. Comparison of changes in serum SCC-Ag levels before and after treatment between the two groups of patients. B. Comparison of serum CYFRA21-1 levels before and after treatment between the two groups. Note: * indicates P<0.05, *** indicates P<0.001. SCC-Ag: squamous cell carcinoma-associated antigen; CYFRA21-1: cytokeratin 19 fragment 21-1.
Comparison of clinical efficacy
In this study, we calculated the changes in clinical efficacy of patients after treatment. Analysis showed that there was no difference in the overall curative effect and effective rate in primary lesions after induction chemotherapy between the two group (P>0.05, Table 2). Comparison of the lymph node induction chemotherapy effect showed that OG held higher overall efficacy and total effective rate in lymph nodes than those in CG (P<0.05, Table 3). Then, the overall curative effect of the two groups of patients after induction chemotherapy was further compared, and it was found that OG held a comparatively higher overall curative effect (P<0.05, Table 4), but there was no difference regarding effective rate between the two groups (P>0.05). Finally, we compared the overall effective rate of the two groups after the whole course of treatment and no statistical difference was found in such index (P>0.05, Table 5).
Table 2.
Efficacy evaluation of primary lesions in patients after induction chemotherapy
| Item | CR | PR | SD | PD | Effective Rate |
|---|---|---|---|---|---|
| Control group (n=41) | 1 | 30 | 8 | 2 | 31 (75.60) |
| Observation group (n=50) | 2 | 40 | 8 | 0 | 42 (84.00%) |
| x2/Z | -1.130 | 0.999 | |||
| P | 0.259 | 0.317 | |||
Note: Complete remission (CR), partial remission (PR), stable disease (SD), progressive disease (PD).
Table 3.
Evaluation of lymph node response in patients after induction chemotherapy
| Item | CR | PR | SD | PD | Effective Rate |
|---|---|---|---|---|---|
| Control group (n=41) | 0 | 28 | 10 | 3 | 28 (68.29) |
| Observation group (n=50) | 1 | 44 | 5 | 0 | 45 (90.00%) |
| x2/Z | -2.752 | 2.586 | |||
| P | 0.006 | 0.009 | |||
Note: Complete remission (CR), partial remission (PR), stable disease (SD), progressive disease (PD).
Table 4.
Overall response evaluation of patients after induction chemotherapy
| Item | CR | PR | SD | PD | Effective Rate |
|---|---|---|---|---|---|
| Control group (n=41) | 0 | 31 | 8 | 2 | 31 (75.60) |
| Observation group (n=50) | 1 | 44 | 5 | 0 | 45 (90.00) |
| x2/Z | -2.026 | 3.389 | |||
| P | 0.043 | 0.065 | |||
Note: Complete remission (CR), partial remission (PR), stable disease (SD), progressive disease (PD).
Table 5.
Evaluation of the overall efficacy of the patients after the full course of treatment
| Item | CR | PR | SD | PD | Effective Rate |
|---|---|---|---|---|---|
| Control group (n=41) | 21 | 11 | 6 | 3 | 32 (78.04) |
| Observation group (n=50) | 25 | 20 | 4 | 1 | 45 (90.00) |
| x2/Z | -0.464 | 2.472 | |||
| P | 0.643 | 0.116 | |||
Note: Complete remission (CR), partial remission (PR), stable disease (SD), progressive disease (PD).
Comparison of adverse reaction
The adverse reactions of two groups were statistically analyzed during the induction chemotherapy phase and the concurrent chemoradiotherapy phase (Table 6). Analytical comparison suggested no marked difference in such indicators (P>0.05, Tables 7, 8).
Table 6.
Adverse reaction statistics
| Item | Statistics of toxic and side effects during induction chemotherapy | ||||
|
| |||||
| Level 0 | Level I | Level II | Level III | Level IV | |
|
| |||||
| Control group (n=41) | |||||
| Malignant Vomiting | 30 | 9 | 2 | 0 | 0 |
| Decreased White Blood Cells | 27 | 5 | 5 | 4 | 0 |
| Thrombocytopenia | 37 | 2 | 2 | 0 | 0 |
| Rash | 39 | 1 | 1 | 0 | 0 |
| Liver Damage | 38 | 2 | 1 | 0 | 0 |
| Observation Group (n=50) | |||||
| Malignant Vomiting | 36 | 10 | 4 | 0 | 0 |
| Decreased White Blood Cells | 35 | 10 | 3 | 2 | 0 |
| Thrombocytopenia | 45 | 3 | 2 | 0 | 0 |
| Rash | 48 | 1 | 0 | 1 | 0 |
| Liver Damage | 48 | 2 | 0 | 0 | 0 |
|
| |||||
| Item | Statistics of toxic and side effects during concurrent chemoradiotherapy | ||||
|
| |||||
| Level 0 | Level I | Level II | Level III | Level IV | |
|
| |||||
| Control Group (n=41) | |||||
| Malignant Vomiting | 23 | 13 | 5 | 0 | 0 |
| Decreased White Blood Cells | 25 | 12 | 3 | 1 | 0 |
| Thrombocytopenia | 38 | 2 | 1 | 0 | 0 |
| Abnormal Liver Function | 39 | 1 | 1 | 0 | 0 |
| Oral Mucositis | 4 | 33 | 2 | 2 | 0 |
| Radiation Dermatitis | 6 | 25 | 8 | 2 | 0 |
| Dry Mouth | 9 | 30 | 2 | 0 | 0 |
| Hearing Loss | 28 | 10 | 3 | 0 | 0 |
| Restricted Mouth Opening | 39 | 2 | 0 | 0 | 0 |
| Observation Group (n=50) | |||||
| Malignant Vomiting | 24 | 16 | 5 | 0 | 0 |
| Decreased White Blood Cells | 28 | 15 | 4 | 3 | 0 |
| Thrombocytopenia | 46 | 2 | 2 | 0 | 0 |
| Abnormal Liver Function | 45 | 5 | 0 | 0 | 0 |
| Oral Mucositis | 12 | 36 | 2 | 0 | 0 |
| Radiation Dermatitis | 10 | 34 | 6 | 0 | 0 |
| Dry Mouth | 14 | 35 | 1 | 0 | 0 |
| Hearing Loss | 38 | 10 | 2 | 0 | 0 |
| Restricted Mouth Opening | 47 | 3 | 0 | 0 | 0 |
Table 7.
Statistical analysis of toxic and side effects during induction chemotherapy
| Item | Malignant Vomiting | Decreased White Blood Cells | Thrombocytopenia | Rash | Abnormal Liver Function |
|---|---|---|---|---|---|
| Control group (n=41) | 11 | 14 | 4 | 2 | 3 |
| Observation group (n=50) | 14 | 15 | 5 | 2 | 2 |
| x2 | 0.015 | 0.178 | 0.001 | 0.041 | 0.477 |
| P | 0.900 | 0.673 | 0.969 | 0.838 | 0.489 |
Table 8.
Statistical analysis of toxic and side effects during concurrent chemoradiotherapy
| Item | Malignant Vomiting | Decreased White Blood Cells | Thrombocytopenia | Abnormal Liver Function | Oral Mucositis | Radiation Dermatitis | Dry Mouth | Hearing Loss | Restricted Mouth Opening |
|---|---|---|---|---|---|---|---|---|---|
| Control group (n=41) | 18 | 16 | 3 | 2 | 37 | 35 | 32 | 13 | 2 |
| Observation group (n=50) | 21 | 22 | 4 | 5 | 38 | 40 | 36 | 12 | 3 |
| x2 | 0.033 | 0.229 | 0.014 | 0.832 | 3.154 | 0.447 | 0.436 | 0.672 | 0.054 |
| P | 0.855 | 0.632 | 0.903 | 0.362 | 0.075 | 0.503 | 0.508 | 0.412 | 0.815 |
Analysis of prognostic factors
Two groups of patients were followed up for 3 years, and no significant difference was observed in the 3-year survival rate between CG and OG (P=0.950, Figure 2A). In terms of disease-free survival time, it was observed to be higher in OG than CG (P=0.008, Figure 2B). Then through multivariate analysis, it was found that clinical stage was an independent prognostic factor affecting OS, while clinical stage and treatment plan were independent prognostic factors affecting PFS (P<0.01, Tables 9, 10).
Figure 2.
Comparison of OS and PFS in patients. A. Comparison of OS between two groups. B. Comparison of PFS between two groups. OS: overall survival; PFS: disease-free survival.
Table 9.
Risk factors for Os
| Factors | Univariate Cox Regression | Multivariate Cox Regression | ||||
|---|---|---|---|---|---|---|
|
|
|
|||||
| P | HR | 95% CI | P | HR | 95% CI | |
| Gender | 0.341 | 0.589 | 0.198-1.753 | |||
| Age | 0.117 | 0.434 | 0.153-1.234 | |||
| T Stage | 0.951 | 0.965 | 0.307-3.030 | |||
| N Stage | 0.249 | 1.487 | 0.757-2.921 | |||
| Clinical Stage | 0.003 | 5.833 | 1.858-18.316 | 0.005 | 4.854 | 1.609-14.643 |
| Pathological Type | 0.946 | 1.015 | 0.662-1.557 | |||
| Scc-Ag | 0.407 | 1.283 | 0.712-2.314 | |||
| Cyfra21-1 | 0.733 | 0.934 | 0.633-1.379 | |||
| Treatment Plan | 0.328 | 0.587 | 0.203-1.704 | |||
Note: Squamous cell carcinoma-associated antigen (SCC-Ag), cytokeratin 19 fragment 21-1 (CYFRA21-1).
Table 10.
Risk factors for PFS
| Factors | Univariate Cox Regression | Multivariate Cox Regression | ||||
|---|---|---|---|---|---|---|
|
|
|
|||||
| P | HR | 95% CI | P | HR | 95% CI | |
| Gender | 0.373 | 0.656 | 0.259-1.661 | |||
| Age | 0.488 | 0.736 | 0.309-1.751 | |||
| T stage | 0.356 | 0.667 | 0.282-1.577 | |||
| N stage | 0.129 | 1.550 | 0.881-2.728 | |||
| Clinical stage | <0.001 | 5.409 | 2.209-13.248 | <0.001 | 4.737 | 1.996-11.241 |
| Pathological type | 0.666 | 1.079 | 0.764-1.524 | |||
| SCC-Ag | 0.107 | 1.491 | 0.917-2.424 | |||
| CYFRA21-1 | 0.755 | 1.053 | 0.761-1.456 | |||
| Treatment plan | 0.015 | 0.324 | 0.131-0.801 | 0.006 | 0.345 | 0.160-0.741 |
Note: Squamous cell carcinoma-associated antigen (SCC-Ag), cytokeratin 19 fragment 21-1 (CYFRA21-1).
Discussion
NPC is derived from nasopharyngeal epithelial cells and is a highly aggressive head and neck malignancy [17]. In recent years, induction chemotherapy, concurrent chemoradiotherapy, and targeted therapy are extensively applied in the clinical treatment of locally advanced NPC [18]. Due to the special influence of the anatomical part of the nasopharynx, its operation is comparatively restricted and difficult [19]. And since NPC is sensitive to emission, radiotherapy is often considered as a common treatment [20]. However, the efficacy of radiotherapy alone for locally advanced NPC is not satisfactory with a 5-year survival rate of only about 35% [21].
Although locally advanced NPC has better short-term efficacy and higher local control rate with the maturity of IMRT, there are still NPC patients undergoing locoregional recurrence and distant transfer on the basis of platinum-based concurrent chemoradiotherapy treatment. To further reduce the recurrence and metastasis of locally advanced NPC, targeted drugs with mild side effects have become a hot topic in the treatment of locally advanced NPC. EGFR is a glycoprotein belonging to the tyrosine kinase type receptor, originally a receptor for epithelial growth factor cell proliferation and signaling. It mainly binds to cell surface ligand and EGFR to undergo dimerization and autophosphorylation [22]. Studies have shown that EGFR was expressed in a variety of solid tumors, and the expression in NPC was up to 80-90% [23]. Nimotuzumab is an IgG1-type humanized monoclonal antibody drug with a unique safety profile and low skin toxicity compared to cetuximab [24]; however, the efficacy of nimotuzumab combined with TP regimen induction therapy in patients with locally advanced NPC has not yet been confirmed. In this study, no marked difference was observed in the efficacy in primary tumor between the two groups of patients after induction chemotherapy. However, further statistics showed that the effective rate in cervical lymph nodes in OG was higher than CG after induction chemotherapy in terms of both the overall efficacy and the effective rate, suggesting that nimotuzumab combined with TP regimen could significantly improve cervical lymph nodes of patients. Moreover, overall efficacy of OG patients after induction chemotherapy was strikingly and statistically improved than that of CG patients. SCCAg exists in normal squamous epithelium and squamous cell carcinoma cells, with only a trace amount presented in normal human serum, but it is significantly elevated in the serum of patients with squamous cell carcinoma, and studies have found that changes in SCCAg expression could reflect the severity of squamous cell carcinoma patients [25]. CYFRA21-1 is widely distributed on the surface of normal tissues such as squamous epithelium. When the cells become malignant, the activated protease accelerates the degradation of the cells, so that a large number of cytokeratin fragments are released into the blood. Most of NPCs originate from the lining squamous epithelium of the nasopharynx, their location is hidden, and the diagnosis is often missed. And the detection of serum CYFRA2121 was proven to be helpful for the early diagnosis of NPC [26]. We detected the tumor markers and found that the serum levels of SCC-Ag and CYFRA21-1 in OG were markedly decreased after treatment and were significantly lower compared with CG. This showed from the other side that the combination of nimotuzumab and TP could achieve short-term efficacy in patients. In the follow-up analysis, however, no marked difference presented in the clinical efficacy of two groups of patients after IMRT treatment, indicating that nimotuzumab combined with TP regimen could improve clinical efficacy of locally advanced NPC patients in short term, but the long-term efficacy still remains unclear.
To determine the effect of nimotuzumab combined with TP regimen on the long-term efficacy of patients, we observed the OS and PFS of the two groups of patients. It suggested that the combination of nimotuzumab and TP had no significant effect on the OS of patients. Previous study of Wang et al. [27] revealed that patients receiving nimotuzumab during concurrent chemoradiotherapy experienced no fluctuation in 5-year OS, which was consistent with our study. However, our further analysis indicated that nimotuzumab combined with TP regimen could benefit the PFS of patients. And through Cox regression, it was found that nimotuzumab combined with TP regimen was a protective factor for PFS of patients. These results all suggested that although nimotuzumab combined with TP regimen couldn’t improve the OS of patients, it upregulated the PFS of patients with locally advanced NPC. In terms of adverse reactions, previous research [28] found that nimotuzumab combined with induction chemotherapy followed by sequential concurrent chemoradiotherapy was effective and well-tolerated in the treatment of locally advanced NPC. At the end of this study, we calculated the incidence of adverse reactions of patients, and found that the occurrence in OG was not statistically different from that in CG, which also suggested that the addition of nimotuzumab to radiotherapy was superior to platinum-based chemotherapy in reducing hematological toxicity. We speculated that the EGFR receptor may be related to the bivalent binding properties of nimotuzumab.
In this study, we determined through relatively comprehensive analysis that nimotuzumab combined with TP regimen induction chemotherapy and sequential concurrent chemoradiotherapy could improve the PFS of patients without increasing the adverse reactions. However, this study still has certain limitations. First of all, due to the inability to query more survival data of patients, the follow-up time of this study was inadequate. Second, the sample size is relatively small compared to large retrospective analysis sample. Therefore, we hope to carry out randomized controlled trials with long-term follow-up in future study to supplement our conclusions.
In conclusion, nimotuzumab combined with TP regimen induction chemotherapy and sequential concurrent chemoradiotherapy could improve the curative effect of locally advanced NPC patients without increasing the incidence of adverse reactions.
Disclosure of conflict of interest
None.
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