Meta-analysis of the efficacy and toxicity of paclitaxel combined with platinum (PTX) and fluorouracil combined with cisplatin (PF) in the treatment of concurrent chemoradiotherapy (CCRT) for unresectable esophageal cancer

doi:10.21203/rs.3.rs-2124206/v1

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Research Article

Meta-analysis of the efficacy and toxicity of paclitaxel combined with platinum (PTX) and fluorouracil combined with cisplatin (PF) in the treatment of concurrent chemoradiotherapy (CCRT) for unresectable esophageal cancer

https://doi.org/10.21203/rs.3.rs-2124206/v1

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Purpose

To systematically evaluate the efficacy and toxicity of paclitaxel/docetaxel combined with platinum (PTX) and fluorouracil combined with cisplatin (PF) in concurrent chemoradiotherapy (CCRT) treatment of unresectable esophageal cancer.

Methods

PubMed, the CNKI database, and Google Scholar were searched by combining subject words and free words through December 31, 2020; quality evaluation and data extraction of the studies that met the inclusion criteria were carried out independently. Stata 11.1 software was used for the meta-analysis comparing the efficacy and treatment-related toxicity of the two regimens.

Result

After screening, a total of 10 studies were included: four were cohort studies, and six were randomized controlled studies (RCT). A total of 1,098 cases were enrolled comprising 1,047 cases (95.4%) of squamous cell carcinoma and 51 cases (4.6%) of adenocarcinoma; 560 cases (51.0%) in the PTX group and 538 cases (49.0%) in the PF group. There was no significant difference in hematological toxicity, gastrointestinal reaction, or radiation pneumonia between the two groups (P = 0.353, 0.741, and 0.321). Radiation esophagitis from the PF regimen was the most serious (P = 0.002). In terms of short-term efficacy, the CR rate of the PTX group was higher than that of PF group (P = 0.029). There was no significant difference in PR rate, ORR rate, or DCR(Disease Control Rate) rate between the two groups (P = 0.599, 0.057, and 0.164). In terms of overall survival rate, the 1-, 2- and 3-year survival rates of the PTX group were higher than those of PF group (P = 0.048, 0.029, and 0.001). There was no significant difference in the 5-year survival rate between the two regimens (P = 0.076). PFS of the PTX group at 1, 2, and 3 years was higher than that of PF group (P = 0.023, < 0.001, and 0.014).

Conclusions

Compared with the PF regimen, the PTX regimen combined with radiotherapy in the CCRT treatment of unresectable esophageal cancer exhibited benefits in clinical CR rate, OS rate, and PFS rate. There was no difference in hematological toxicity, gastrointestinal reaction, or acute radiation pneumonia between the two regimens. The PTX regimen had lower esophageal toxicity and therefore might be the preferred concurrent chemotherapy regimen for esophageal squamous cell carcinoma.

esophageal cancer

concurrent chemoradiotherapy

paclitaxel

fluorouracil

efficacy

toxicity

Concurrent chemoradiotherapy (CCRT) is standard therapy for patients with localized carcinoma of the esophagus who are selected for nonsurgical treatment (category 1A) [1–3]. However, the locoregional failure rate after CCRT is high, and the long-term survival status is not optimistic. Chemotherapy plays an important role in definitive chemoradiotherapy strategies. The commonly used clinical concurrent chemotherapy regimens include fluorouracil and cisplatin, taxane and platinum, gemcitabine and platinum, and irinotecan. Among these, fluorouracil + cisplatin (PF) is the most classic scheme and has been used as the preferred first-line treatment according to the results of the RTOG85-01 trial[1]. Squamous cell carcinoma is the main pathological type (> 90%) of esophageal cancer in Asian countries. Therefore, most scholars prefer to choose paclitaxel combined with platinum (PTX) in clinical trial design and practical treatment [4–7]. This is also a first-line recommendation in the CSCO guidelines. In our study, there remained insufficient evidence to confirm the superiority or inferiority of the two schemes, especially for esophageal squamous cell carcinoma. Based on the background information, we designed this meta-analysis to evaluate the differences in overall survival benefit and toxicity of the PTX regimen and PF regimen in the context of precise radiotherapy, to provide a basis for clinical treatment options.

Literature search

PubMed, CNKI, and Google Scholar were searched by combining subject words and free words through December 31, 2020. The keywords used were as follows: "esophageal or oesophageal," "cancer or cancer or neoplast," "chemoradiotherapy," "concurrent," and "paclitaxel or docetaxel." After obtaining the search results, we carefully read the title and abstract and filtered out research that was not within the scope of this analysis.

Literature inclusion criteria

(1) Study type was CCRT for esophageal cancer, cohort studies or randomized controlled trials (RCTs) comparing PTX and PF regimens, in Chinese or English. (2) The radiotherapy techniques used in the research were three-dimensional conformal or intensity-modulated radiotherapy. (3) The research observation indicators were the therapeutic effect and toxicity of the two schemes. (4) Participants: esophageal cancer (squamous cell carcinoma/adenocarcinoma) was confirmed by pathological diagnosis, with no exclusion based on gender, age, or clinical stage.

Exclusion Criteria

The exclusion criteria were as follows: (1) co-study of other malignant tumors or diseases at the same time; (2) neoadjuvant or postoperative adjuvant chemoradiotherapy studies; (3) those that did not include the data required for this study; and (4) the combination regimen that included drugs other than PTX and PF.

Intervention Measures

The experimental group (PTX group) was treated with paclitaxel/docetaxel (taxanes) combined with platinum-based chemotherapy for concurrent radiotherapy, and the control group (PF group) was treated with cisplatin combined with fluorouracil for concurrent radiotherapy.

Observation Indices And Reference Variables

(1) Safety: Grade 3 and above toxic reactions (hematological toxicity, gastrointestinal reaction, radiation pneumonia, and radiation esophagitis) of the two chemotherapy regimens were collected from the included studies. (2) Short-term therapeutic effect included Complete Remission (CR), Partial Response (PR), Objective Response Rate (ORR), and Disease Control Rate (DCR) based on RESICT standards. (3) Overall Survival (OS) and Progression-Free Survival (PFS) included 1-, 2-, 3-, and 5-year overall survival rate; 1-, 2-, and 3-year disease progression-free survival rate.

Quality Evaluation

The quality of the included literature was evaluated. The cohort study used the Newcastle-Ottawa Scale (Newcastle-Ottawa Scale, NOS) with 1–3 as low quality, 4–6 as medium quality, and 7–9 as high quality. The Jadad scale was used to evaluate the quality of randomized controlled trials (RCTs), and the evaluation was based on the randomization scheme, concealment, blinding, the reasons for withdrawal and loss to follow-up, and the number of cases. A score of 0–5 was used. A score of ≤ 2 was regarded as a low-quality study, and a score of ≥ 3 was regarded as a high-quality study. Disagreements were resolved through discussion or soliciting opinions from a third party. The specific scoring results are shown in Table 1.

Table 1

Characteristics of included studies
Author	Publication	Nation	Pathology	Clinical stage	Cases (PTX/PF)	Chemotherapy regimen	Radiotherapy dose	Research	NOS	Jadad
Size Chen	2011	China	SCC	III-IVa	48 (24/24)	Docetaxel + DDP vs. Cisplatin + 5-FU	60Gy	RCT	--	2
Tao Zhao	2012	China	SCC	II-IVa	90 (45/45)	Docetaxel + Cisplatin vs. 5-FU + Cisplatin	50.4Gy	RCT	--	2
Wencui Ju	2012	China	SCC	--	72 (36/36)	Paclitaxel + Cisplatin vs. 5-Fu + Cisplatin	60-66Gy	RCT	--	3
Minghua Bai	2013	China	SCC	IIb-IVb	74 (36/38)	Docetaxel + Cisplatin vs. 5-Fu + Cisplatin	60-70Gy	RCT	--	2
J. Honing	2014	Netherlands	AC/SCC	I-IVa	102 (55/47)	Paclitaxel + Carboplatin vs. 5-FU + Cisplatin	46.8-70Gy	Cohort	7	--
Liqing Zhang	2016	China	SCC	IIa-III	61 (31/30)	Paclitaxel + Cisplatin vs. 5-Fu + Cisplatin	64Gy	RCT	--	2
Peng Zhang	2016	China	SCC	II-IVa	317 (161/156)	Docetaxel + Cisplatin vs. 5-FU + Cisplatin	50–70 Gy	Cohort	9	--
Guofang Hu	2016	China	SCC	IIb-IIc	202 (105/97)	Paclitaxel + Cisplatin vs. 5-FU + Cisplatin	54–60 Gy	Cohort	7	--
Yujia Zhu	2017	China	SCC	II-IVa	86 (45/41)	Docetaxel + Cisplatin vs. Cisplatin + 5-FU	60-64Gy	RCT	--	3
Chunyue Huang	2020	China	SCC	I-IVb	46 (22/24)	Docetaxel or Paclitaxel + Cisplatin or Carboplatin vs. 5-Fu + Cisplatin	50–66 Gy	Cohort	7	--
SCC: Squamous cell carcinoma; AC: Adenocarcinoma; and RCT: Randomized controlled trials.

Data Extraction

Two reviewers independently extracted the included research data, and after cross-checking, inconsistent results were resolved through discussion or soliciting opinions from a third party. Data extraction content included: basic information, sample size, pathology type, chemotherapy regimen, radiotherapy dose, study type, short-term therapeutic effect, OS rate, PFS rate, and grade 3 or above toxicity. For those whose long-term survival rates could not be obtained directly, the Engauge-Digitizer software was used to extract the information from the Kaplan-Meier curve.

Statistical analysis

Stata11.1 was used, Relative risk (RR) was selected as the effect index, and 95% confidence intervals (CI) were calculated. To judge the rationality of the combined analysis of the test groups, the Chi-square test was used to test for heterogeneity among the test groups. A random effects model (REM) was used if the heterogeneity was significant (P < 0.05 or I² > 50%); otherwise, a fixed effects model (FEM) was used. If the heterogeneity was large, the causes and sources of heterogeneity were further analyzed and if necessary, subgroup analysis and sensitivity analysis were performed to test the stability of the results. Begg analysis of the included studies was performed using Stata 11.1. Publication bias was judged based on the Begg test results. Publication bias was considered when P < 0.05.

Basic information on literature retrieval

First, the title and abstract of the preliminary literature were searched, and qualified literature was screened. Then, the full text was read, and a determination was made as to whether the study met the inclusion criteria. Clinical trials that did not meet the inclusion criteria were excluded. The terms "esophageal or oesophageal," "carcinoma or cancer or neoplasm," "chemoradiotherapy," "concurrent," and "paclitaxel or docetaxel" were used as the search terms. The search retrieved 567 potentially relevant articles, 51 relevant articles were identified by reading the abstracts, and 10 articles were ultimately included after reading the full text. The specific process is shown in Fig. 1.

Basic Characteristics Of The Included Studies

A total of 10 papers [8–17] were included in the systematic evaluation (Table 1), of which nine studies were from China, one from the Netherlands, four were cohort studies, and six were randomized controlled studies (RCTs). A total of 1,098 patients with esophageal cancer were included in the systematic evaluation, the pathological type in nine studies was squamous cell carcinoma and one had both squamous and adenocarcinoma, with a cumulative total of 1,047 cases (95.4%) of squamous carcinoma and 51 cases (4.6%) of adenocarcinoma. There were 560 cases (51.0%) in the PTX group and 538 cases (49.0%) in the PF group. Statistical tests of the baseline data in the PTX and PF groups were reported in all 10 studies, and all were comparable. The radiation dose and the tumor stages differed among the studies, but there was no difference in the comparative results after pooling the 10 studies. All of the studies provided data on chemoradiotherapy-related hematological toxic reactions (myelosuppressive reactions in leukocytes, platelets, and hemoglobin), gastrointestinal reactions (nausea, vomiting, and diarrhea), radiation pneumonia, and radiation esophagitis. Seven studies reported the short-term therapeutic effects on the disease including CR, PR, ORR, and DCR. All 10 studies reported 1-, 2-, 3-, and 5-year overall survival rates. Six studies reported 1-, 2-, and 3-year PFS rates or survival curves. The basic characteristics of the included studies are shown in Table 1.

Comparison Of Toxicity Between The Ptx And Pf Regimens With Ccrt

All 10 studies reported hematological toxicity. Nine reported gastrointestinal reactions, six reported radiation pneumonia, and eight reported radiation esophagitis, all were analyzed at the cut-off point of ≥ 3 grade toxicities. In hematological toxicity, there was significant heterogeneity among the 10 studies (heterogeneity test: I² = 68.6%, P = 0.001), which was analyzed by REM. After all the studies were combined, the overall test results showed that the hematological toxicity of the two regimens was similar, and there was no overall difference [RR = 1.22, 95% CI (0.80, 1.86), P = 0.353, Fig. 2A]. Gastrointestinal reaction and radiation pneumonitis were analyzed by the FEM (I² = 0%, P = 0.812, 0.519). The results showed that there was no significant difference in gastrointestinal reaction or radiation pneumonitis between the two regimens combined with CCRT [RR = 0.94, 95% CI (0.65, 1.35), P = 0.741, Fig. 2B; RR = 0.70, 95% CI (0.35, 1.41), P = 0.321, Fig. 2C]. Eight studies provided data on radiation esophagitis. The FEM (I² = 44.1%, P = 0.085) was used to analyze the data. The overall test results indicated that the PF regimen resulted in stronger esophageal toxicity [RR = 0.63, 95% CI (0.47, 0.85), P = 0.002, Fig. 2D].

Comparison Of The Short-term Therapeutic Effect Of The Ptx And The Pf Regimens With Ccrt

Six studies provided data on the CR, PR, and DCR of tumors and seven studies provided ORR data; specific efficacy data are shown in Table 2. After combined analysis, the results showed a difference in CR rates between the two regimens, with a range of 17.14–33.33% for the PTX regimen and 7.22–29.27% for the PF regimen; the former was higher than the latter [RR = 1.43, 95% CI (1.04, 1.97), P = 0.029]. There was no significant difference between the two regimens in terms of PR rate, ORR rate, or DCR rate.

Table 2

Results of meta-analysis of the short-term therapeutic effects of the PTX and PF regimens combined with CCRT
Index	Effect model	Test value	Short-term therapeutic effect (%)		RR	95%CI	P
Index	Effect model	Test value	PTX	PF	RR	95%CI	P
Complete Remission (CR)	Fixed effects model	I² = 0%, P = 0.771	17.1–33.3	7.22–29.27	1.43	1.04–1.97	0.029
Partial Remission (PR)	Fixed effects model	I² = 0%, P = 0.830	35.2–69.4	28.89–72.22	1.05	0.88–1.25	0.599
Objective Response Rate (ORR)	Random effects model	I² = 50.6%, P = 0.059	52.4–91.7	38.14–88.89	1.14	1.00–1.30	0.057
Dose Control Rate (DCR)	Fixed effects model	I² = 16.4%, P = 0.308	88.9–97.2	80.0–100	1.03	0.99–1.08	0.164

Comparison of overall survival (OS) rate and progression-free survival (PFS) rate between the PTX and PF regimens with CCRT

The reported survival benefits included 1-, 2-, 3-, and 5-year OS rates and 1-, 2-, 3-year PFS rates. Among these, if the year-by-year OS/FPS data were not specifically reported, then the data were extracted from the Kaplan-Meier curve using Engauge-Digitizer software. The specific OS and PFS meta-analysis results from the 10 studies are shown in Table 3, Figs. 3A–D, and Fig. 4A–C. The results of the meta-analysis showed that the 1-, 2-, and 3-year overall survival rates of the PTX regimen were higher than those of the PF regimen. For long-term survival data, six studies [11–15, 17] reported the 5-year OS rate, and of these, four studies [5, 7, 9, 11] favored a long-term survival benefit of the PTX program, one study [12] tended to benefit from the PF regimen, and one study [14] clearly showed that the 5-year overall survival rate of the PTX regimen was significantly better than that of the PF regimen. The combined meta-analysis results showed that there was no significant statistical difference in 5-year survival rate between the two CCRT regimens. However, the data suggested that the PTX program had a trend toward a benefit [RR = 1.50, 95% CI (0.96, 2.35), P = 0.076, Fig. 3D]. In terms of disease progression-free survival, five studies reported year-on-year PFS data, and one study provided DFS data (in this study, it was regarded as PFS), the combined meta-analysis results showed that the 1-, 2-, and 3-year PFS of the PTX program were significantly higher than the PF program (P = 0.023, < 0.001, 0.014), as shown in Fig. 4A-C.

Table 3

Meta-analysis of survival rates of the PTX and PF regimens combined with CCRT
Index	Effect model	Test value	Survival rate range (%)		RR	95%CI	P
Index	Effect model	Test value	PTX	PF	RR	95%CI	P
1-year survival rate	Fixed effects model	I² = 0%, P = 0.742	59.2–95.0	63.6–93.6	1.06	1.00–1.13	0.048
2-year survival rate	Random effects model	I² = 49.7%, P = 0.037	35.0–72.0	27.0–86.2	1.19	1.02–1.39	0.029
3-year survival rate	Fixed effects model	I² = 0.0%, P = 0.473	31.9–60.1	22.9–62.6	1.28	1.10–1.48	0.001
5-year survival rate	Random effects model	I² = 54.6%, P = 0.051	14.1–39.4	8.2–27.8	1.50	0.96–2.35	0.076
1-year PFS rate	Fixed effects model	I² = 0%, P = 0.448	44.9–82.0	48.9–77.4	1.13	1.02–1.25	0.023
2-year PFS rate	Fixed effects model	I² = 0%, P = 0.474	27.8–69.4	12.9–55.0	1.50	1.25–1.79	< 0.001
3-year PFS rate	Fixed effects model	I² = 9.7%, P = 0.354	13.8–49.3	8.3–54.9	1.33	1.06–1.67	0.014

Sensitivity And Bias Analysis

Sensitivity analysis was performed due to the high heterogeneity of hematological toxicity, ORR rate, 2-year overall survival rate, and 5-year overall survival rate. The combined effect results after deleting the more divergent articles (Yujia Zhu's study [16]) are shown in Table 4. Results showed that the heterogeneity in ORR rate and 2-year overall survival was reduced, but the heterogeneity of hematological toxicity research remained strong. After deleting Yujia Zhu's study [16], the meta-analysis results showed that the objective remission rate and 2-year overall survival rate of the PTX regimen remained higher than those of the PF regimen [RR = 1.19, 95% CI (1.03, 1.37), P = 0.020; RR = 1.29, 95% CI (1.14, 1.45), P ≤ 0.001]. After deleting the study by Peng Zhang et al. [14], which had the largest variability, the 5-year survival rate results continued to show no significant difference in the long-term survival rate of the two programs [RR = 1.24, 95% CI (0.85, 1.81), P = 0.270].

Table 4

Sensitivity analysis
Items		Heterogeneity analysis I²	Heterogeneity P value	RR	95% CI		P
Hematological toxicity	Yujia Zhu (2017)	59.30%	0.012	1.084	0.727	1.617	0.693
Objective response rate	Yujia Zhu (2017)	40.20%	0.137	1.186	1.028	1.368	0.020
2-year survival rate	Yujia Zhu (2017)	0.00%	0.800	1.286	1.144	1.446	0.000
5-year survival rate	Peng Zhang (2016)	12.00%	0.337	1.237	0.848	1.805	0.270
RR: Relative risk.

Publication bias was judged based on the results of Begg's test for the included studies. Funnel plots were drawn with SElogRR and logRR as horizontal and vertical coordinates, respectively. The results showed that only the ORR rate indicator was biased, and the funnel plot of Begg's analysis was not symmetrically distributed.

We applied the trim-and-fill analysis method to evaluate the impact of publication bias on the results. If the impact is not large, the results are more robust, and if the impact is large (becomes insignificant), the publication bias must be discussed in the results. In this study, the ORR exhibited publication bias. According to the combination of RR values of the FEM and REM (see Table 5), there was a statistical difference between the PTX and PF groups (P < 0.05) (Fig. 5A). However, there was no significant statistical difference between the two after the cut-and-fill method was applied (P > 0.05) (Fig. 5B). Therefore, this conclusion is not robust enough and requires further research.

Table 5

Results before trim-and-fill analysis
Method	Pooled Est	95%CI		Asymptotic
Method	Pooled Est	Lower	Upper	Z value	P value
Fixed	0.088	0.001	0.175	1.977	0.048
Random	0.118	0.002	0.234	1.991	0.046

For locally advanced unresectable esophageal cancer, CCRT is the first-line recommended treatment mode in Europe, America, and Asian countries including China (1A evidence) [1–3]. Chemotherapy with fluorouracil and cisplatin and concurrent radiotherapy of 50.4 Gy are considered the standard scheme [1, 3]. In Europe and the USA, esophageal cancer cases are predominantly adenocarcinoma (> 70%), and fluorouracil + cisplatin is the preferred choice of therapeutic agents. Therefore, fluorouracil + cisplatin has been recommended as the first choice in the NCCN chemotherapy recommendations for both locally advanced esophageal cancer and metastatic esophageal cancer. However, the main pathological type (> 90%) of esophageal cancer in Asian countries is squamous cell carcinoma. In clinical trial design and practical treatment, most scholars are more inclined to choose taxane combined with platinum drugs [4–7]; this is also a first-line recommendation in the CSCO guidelines. In the current study, especially for esophageal squamous cell carcinoma, there remained insufficient evidence to confirm the superiority or inferiority of the two regimens. Based on the background information, we conducted this meta-analysis to evaluate the overall difference in survival benefit and toxicity of the PTX and PF regimens combined with concurrent radiotherapy in the context of precision radiotherapy, to provide a basis for the selection of clinical treatment.

In terms of toxicity and side effects, 5-fluorouracil (5-FU) and its derivatives are anti- metabolic anti-tumor drugs. They are recommended in the treatment of multiple system tumors because of their wide anti-tumor spectrum and can be used alone or in combination with other anti-tumor drugs. The main adverse reactions include serious gastrointestinal reactions and bone marrow suppression; others include alopecia, hepatotoxicity, allergic skin reactions, hand-foot syndrome, and oral ulcers/stomatitis. Taxanes are cytotoxic anti-tumor drugs that act on the microtubule/tubulin system. They can block the G2 and M phases of the cell cycle and inhibit the mitosis and proliferation of cancer cells. Further, in vitro experiments proved that paclitaxel exerts a significant radiosensitization effect. In addition to bone marrow suppression, gastrointestinal reactions, cardiovascular, and liver toxicity, common adverse drug reactions also include allergic reactions (paclitaxel), body fluid retention (docetaxel), and neurotoxicity. When chemotherapy is applied concurrently with radiotherapy, radiation esophagitis and radiation pneumonitis may be aggravated. In this meta-analysis, treatment-related toxicity that could be obtained and statistically compared included hematological toxicity (myelosuppressive reaction of white blood cells, platelets, and hemoglobin), gastrointestinal reactions (nausea, vomiting, diarrhea), and acute radiation pneumonitis and radiation esophagitis. These were analyzed with a ≥ grade 3 toxic reaction as the cut-off point. Results showed no significant difference between the two regimens in common chemotherapy-related adverse events (hematological toxicity and gastrointestinal reactions) and radiation pneumonitis synergized by radiotherapy and chemotherapy. In terms of radiation esophagitis, eight studies provided comparable data, six of the studies [8, 9, 10, 13, 15, 17] did not show significant differences in comparison (four studies favored the PF regimen for more severe esophageal toxicity), two studies [11, 14] showed a higher incidence of grade ≥ 3 radiation esophagitis with the PF regimen, and an overall test of the combined results of the eight studies suggested a more severe esophageal toxicity with the PF regimen. This may be related to the damaging effects of fluorouracil on the proliferating mucosal cells of the digestive tract (stomatitis, oral ulcers, glossitis, esophagitis). Therefore, when the PF regimen is combined with radiotherapy to treat esophageal cancer concurrently, the occurrence of radiation esophagitis should be an aspect of clinical treatment and nursing care.

In terms of treatment benefits, the results of this meta-analysis showed that the PTX regimen had a higher CR rate, 1-, 2-, 3-year overall survival rates, and progression-free survival rate than the PF regimen when combined with concurrent radiotherapy in the treatment of unresectable esophageal cancer. Unfortunately, in the comparison of long-term survival indicators, there was no significant difference in the 5-year survival rate between the two regimens. Of the 10 studies that entered the meta-analysis, six [11–15, 17] reported 5-year overall survival rates ranging from 14.1–39.4% for the PTX regimen and 8.2–27.8% for the PF regimen. Among them, four [6, 13, 15, 17] favored the long-term survival benefit of the PTX regimen, one [12] favored the benefit of the PF regimen, and one study [14] clearly showed that the 5-year overall survival rate of the PTX regimen was significantly superior to PF scheme. Although the combined analysis result was negative, the data suggested that the PTX program had a trend toward a long-term survival benefit [RR = 1.50, 95% CI (0.96, 2.35), P = 0.076]. Combined with the comparison results of other therapeutic effects and survival indicators, the study suggests that the PTX regimen is the optimal regimen for CCRT in esophageal squamous cell carcinoma.

Limitations of this study included: 1. the radiation dose, clinical stage, and specific drugs used in studies included in the meta-analysis (five studies in the PTX protocol group used docetaxel + platinum, four studies used paclitaxel + platinum, and one both) were not consistent. 2. The cumulative number of cases was small, and the sum of the number of cases enrolled in both protocols in the six RCT studies was less than 100 (48–90 cases). 3. Most studies did not describe the specific allocation method and allocation concealment in detail; all studies did not mention whether a blinding method was used and did not use intention analysis on the results. All of the above may cause bias in the data analysis results. In addition, nine of the 10 studies were from China and one was from the Netherlands. Therefore, the meta-analysis may be more representative of the results of Asian esophageal squamous cell carcinoma.

In summary, compared with the PF regimen, the PTX regimen combined with concurrent radiotherapy for unresectable esophageal cancer may have therapeutic benefits in terms of clinical CR rate, OS, and PFS. There was no difference in hematological toxicity, gastrointestinal reaction, or acute radiation pneumonia between the two regimens; the PTX regimen had lower esophageal toxicity and may be the preferred CCRT regimen for esophageal squamous cell carcinoma. However, this conclusion requires further confirmation through prospective randomized controlled studies of many cases.

Compared with the PF regimen, the PTX regimen combined with radiotherapy in the concurrent treatment of unresectable esophageal cancer has benefits in clinical CR rate, OS rate, and PFS rate. There was no difference in hematological toxicity, gastrointestinal reaction, or acute radiation pneumonia between the two regimens. The PTX regimen had lower esophageal toxicity. Therefore, this study suggests it as the preferred concurrent chemotherapy regimen for esophageal squamous cell carcinoma.

Conflicts of interest statement

The authors declare that they have no conflicts of interest.

Acknowledgments

We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.

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01 Feb, 2023
Editor assigned by journal
30 Jan, 2023
First submitted to journal
01 Oct, 2022

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Meta-analysis of the efficacy and toxicity of paclitaxel combined with platinum (PTX) and fluorouracil combined with cisplatin (PF) in the treatment of concurrent chemoradiotherapy (CCRT) for unresectable esophageal cancer

Status:

Version 1

Abstract

Purpose

Methods

Result

Conclusions

Figures

Introduction

Methods

Exclusion Criteria

Intervention Measures

Observation Indices And Reference Variables

Quality Evaluation

Data Extraction

Statistical analysis

Results

Basic information on literature retrieval

Basic Characteristics Of The Included Studies

Comparison Of Toxicity Between The Ptx And Pf Regimens With Ccrt

Comparison Of The Short-term Therapeutic Effect Of The Ptx And The Pf Regimens With Ccrt

Sensitivity And Bias Analysis

Discussion

Conclusions

Declarations

References

Status:

Version 1