Efficacy and safety of integrated Chinese and Western medicine in advanced pancreatic cancer: A double-center retrospective cohort study

Abstract

BACKGROUND

Advanced pancreatic cancer (PC) is associated with a poor prognosis. The integration of Chinese and Western medicine (ICWM) has shown promising clinical efficacy. Nonetheless, the existing body of research assessing the efficacy and safety of this integrative approach is limited, hindering the provision of robust evidence-based support for clinical decision-making.

AIM

To assess the short-term and long-term efficacy and safety of ICWM compared with Western medicine (WM) as a standalone treatment for advanced PC.

METHODS

We enrolled 136 patients with advanced PC admitted to Henan Provincial Hospital of Traditional Chinese Medicine and Henan Provincial People’s Hospital from 2019 to 2024. Patients were randomly assigned to the ICWM or WM group (n = 66 or n = 70, respectively) according to treatment modality. The long-term efficacy was evaluated using survival analyses. Short-term efficacy was assessed by analyzing the tumor response, serum tumor markers, and immune function before and after treatment. Treatment safety was assessed by monitoring bone marrow suppression and hepatic and renal function impairment.

RESULTS

The median overall survival was 12.91 months and 10.64 months in the ICWM and WM groups, while the median progression-free survival was 5.12 months and 3.55 months, respectively. The disease control rate was significantly higher in the ICWM group than that in the the WM group, while the myelosuppression was significantly milder. The serum tumor markers carbohydrate antigen (CA) 19-9 and CA125 showed a significant downward trend before and after treatment in the ICWM group, whereas only CA19-9 showed a significant decrease in the WM group. Post-treatment, both groups showed an upward trend in natural killer cells and CD3+, CD4+, and CD4+/CD8+ lymphocytes compared with pre-treatment, with the ICWM group exhibiting a more pronounced increase. The two groups showed no significant differences in hepatic and renal function impairment.

CONCLUSION

ICWM extended survival in patients with advanced PC, improved long-term efficacy, controlled local lesions, reduced serum tumor markers, enhanced immune function, and improved short-term outcomes, with a favorable safety profile.

Key Words: Advanced pancreatic cancer; Integrated Chinese and Western medicine; Retrospective cohort study; Survival duration; Short-term outcomes; Long-term outcomes; Safety

Core Tip: Advanced pancreatic cancer (PC) is associated with poor prognosis. In this double-center retrospective cohort study, the median survival time in the Western medicine (WM) group was 10.67 months, while the integration of Chinese and WM group demonstrated an additional 2.24 months of survival. This breakthrough exceeded the conventional 12-month median survival time threshold for PC, nearing the survival outcomes achieved with targeted immunotherapy and combination chemotherapy, which are at the forefront of precision treatments. These findings suggest that integrated Chinese and WM models may provide survival advantages to patients with advanced PC.

INTRODUCTION

Pancreatic cancer (PC) is one of the most aggressive malignancies of the gastrointestinal tract and is characterized by an insidious onset, high invasiveness, and rapid progression. Approximately 90% of patients with PC are diagnosed at intermediate or advanced stages[1]. However, the development of effective therapeutic strategies for PC is slow and lags significantly behind that for other malignancies. Traditional chemotherapy regimens, the first-line treatment for advanced PC[2], yield a 5-year survival rate of only 2%-9%[3], with reports revealing that PC is the second leading cause of cancer-associated death[4].

The therapeutic approach of traditional Chinese medicine (TCM) is rooted in the harmonization of yin-yang and qi-blood. This is achieved through multifaceted actions, including modulation of the immune system, remodeling of the tumor microenvironment, and inhibition of tumor microvessels, which collectively enhance the host immune defense and potentiate the efficacy of antitumor therapies[5,6]. Mechanistic investigations demonstrated that a novel artemisinin derivative, ZQJ29, induces ferroptosis in PC cells via PARP1 inhibition, highlighting its potential as a lead compound in the development of novel anticancer drug development[7]. Clinical research on the TCM compound Qingyi Xiaoji Formula has indicated its utility in PC treatment by mitigating chemotherapy-induced toxicity, improving patient quality of life, and alleviating common side effects[8]. Despite these promising findings, the integration of TCM with conventional therapies requires validation through more robust clinical trials to establish their therapeutic efficacy and safety profile, and thus facilitate their widespread adoption in PC management. Therefore, in this retrospective cohort study, we evaluated the efficacy and safety of integration of Chinese and Western medicine (ICWM) vs Western medicine (WM) alone for the treatment of advanced PC, with the aim to provide scientific evidence for the broader application of integrated approaches in treatment.

MATERIALS AND METHODS

General data

A total of 136 patients with advanced PC who were admitted to Henan Provincial Hospital of Traditional Chinese Medicine and Henan Provincial People’s Hospital between 2019 and 2024 were included in this study. The patients were divided into two distinct groups according to the treatment modality: (1) The combined ICWM group (n = 66); and (2) The WM group (n = 70). The ICWM group comprised 37 males and 29 females; 36 patients were under 65 years of age, and 30 were 65 years or older. The performance status (PS) scores were 0 and 1 in 45 patients and ≥ 2 in 21 patients. Histologically, 62 cases were ductal adenocarcinomas and 4 cases were of other types. Differentiation levels were low in 50 cases, moderate in 15, and high in one. The distribution by pancreatic location was as follows: (1) Head (36 cases); (2) Body (4 cases); (3) Tail (11 cases); and (4) Mixed locations (15 cases). The TNM stage was stage III in 11 cases and stage IV in 55; additional findings included 8 cases of ascites and 39 cases of hepatic impairment. Treatment regimens included chemotherapy in 48 patients, chemotherapy combined with targeted therapy in 4, chemotherapy with immunotherapy in 1, radiofrequency ablation in 6, and radioactive seed implantation brachytherapy in 7. The WM group comprised 39 males and 31 females. Thirty-four patients were < 65 years, and 36 were ≥ 65 years. The PS scores were 0 and 1 in 56 patients and ≥ 2 in 14 patients. Histologically, 63 cases were ductal adenocarcinomas, with seven cases of other types. The differentiation levels included 46 cases with low differentiation, 20 with moderate differentiation, and four with high differentiation. The tumor locations were as follows: (1) Pancreatic head (51 cases); (2) Body (three cases); (3) Tail (seven cases); and (4) Mixed sites (nine cases). TNM staging revealed stages III and IV disease in 12 patients and 58 patients, respectively. Ascites was present in eight cases and hepatic impairment in 46 cases. Treatment options included chemotherapy in 50 patients and chemotherapy combined with targeted therapy in two patients. Chemotherapy was combined with immunotherapy in eight cases, radiofrequency ablation in five, and radioactive seed implantation brachytherapy in five. There were no statistically significant differences in the general data of the two groups (P > 0.05), indicating comparability (Table 1). This study was approved by the Medical Ethics Committee of the Henan Provincial Hospital of Traditional Chinese Medicine.

Table 1 Patient characteristics, n (%).

Characteristics	Integration of Chinese and Western medicine group (n = 66)	Western medicine group (n = 70)	χ2	P value
Gender			0.002	0.968
Female	29 (43.9)	31 (44.3)
Male	37 (56.1)	39 (55.7)
Age (years)			0.485	0.486
< 65	36 (54.5)	34 (48.6)
≥ 65	30 (45.5)	36 (51.4)
Eastern Cooperative Oncology Group Performance Status			2.483	0.115
0 and 1	45 (68.2)	56 (80.0)
2	21 (31.8)	14 (20.0)
Histological type			0.709	0.400
Ductal adenocarcinoma	62 (93.9)	63 (90.0)
Other	4 (6.1)	7 (10.0)
Differentiation grade			2.566	0.277
Poorly differentiated	50 (75.8)	46 (65.7)
Moderately differentiated	15 (22.7)	20 (28.6)
Well differentiated	1 (1.5)	4 (5.7)
Primary site			5.005	0.171
Head of pancreas	36 (54.5)	51 (72.9)
Body of pancreas	4 (6.1)	3 (4.3)
Tail of pancreas	11 (16.7)	7 (10.0)
Mixed	15 (22.7)	9 (12.9)
TNM stage			0.636	0.425
Stage III	11 (16.7)	12 (17.1)
Stage IV	55 (83.3)	58 (82.9)
Ascites presence
Present	8 (12.1)	8 (11.4)
Absent	58 (87.9)	62 (88.6)
Hepatic impairment
Present	39 (59.1)	46 (65.7)
Absent	27 (40.9)	24 (34.3)
Treatment regimen			6.464	0.167
Chemotherapy	48 (72.7)	50 (71.4)
Chemotherapy plus targeted therapy	4 (6.1)	2 (2.9)
Chemotherapy plus immunotherapy	1 (1.5)	8 (11.4)
Radiofrequency ablation	6 (9.1)	5 (7.1)
Radioactive seed implantation brachytherapy	7 (10.6)	5 (7.1)

Western medical diagnostic criteria

The diagnostic criteria followed the European Society of Medical Oncology Clinical Practice Guidelines for PC, published in September 2023 by the European Society of Medical Oncology[9]. Diagnosis was confirmed through pathological examination of PC or clinical diagnosis based on symptoms, physical signs, laboratory tests, and imaging studies.

Clinical staging criteria

The clinical staging criteria followed the PC staging standards in the 8th edition of the American Joint Committee on Cancer Staging Manual[10], which includes patients classified as having stage III or IV PC.

Inclusion criteria

The inclusion criteria were as follows: (1) Patients who met the diagnostic criteria for WM and were diagnosed with primary PC through pathological or imaging examinations; (2) Aged ≥ 18 years; (3) Patients who have received at least three courses of TCM treatment within 6 months of the initial consultation; (4) Detailed treatment plans, efficacy evaluation results, and adverse reaction records; and (5) Confirmed date of death or last follow-up.

Exclusion criteria

The exclusion criteria were as follows: (1) Patients with concurrent primary malignancies; (2) Patients with autoimmune or active infections; (3) Eastern Cooperative Oncology Group Performance Status score of ≥ 3; (4) Pediatric cases, pregnant individuals, or those with severe mental health conditions; (5) Patients who have severe infections or other organ diseases; and (6) Patients with significant deficiencies in clinical data or relevant examinations.

Exclusion after enrollment

(1) The inclusion criteria were met, but the treatment course was insufficient for analysis; and (2) Patients for whom time to progression and overall survival (OS) could not be assessed.

Treatment methods

The ICWM group used Chinese medicine as the foundation for each hospitalization combined with multidisciplinary treatments, including chemotherapy, targeted therapy, and immunotherapy, tailored to clinical needs. TCM treatments were administered in 21-28-day cycles, with evaluations performed after two cycles. For patients with stable disease (SD), subsequent treatment intervals may be extended, and for those with disease progression, treatment regimens will be adjusted. Western medical treatment followed the National Comprehensive Cancer Network guidelines and incorporated chemotherapy, radiofrequency ablation, particle implantation, targeted therapy, and immunotherapy. Follow-up continued until July 31, 2025.

Observation indicators

Long-term efficacy: OS was defined as the time from diagnosis of advanced PC to death from any cause. Deceased subjects were considered to have complete data, and OS was defined as the time span from diagnosis until death. Incomplete data included survivors and those who were lost to follow-up. Survivors were treated as right-censored, with OS defined as the time from diagnosis to the last follow-up visit; subjects lost to follow-up were treated as left-censored, and OS was defined as the time from diagnosis to the last follow-up visit.

Progression-free survival (PFS) was defined as the time from the diagnosis of advanced PC until the first tumor progression, death (from any cause), or the end of follow-up.

Short-term efficacy: (1) Efficacy in solid tumors: Progressive disease (PD), SD, partial response (PR), and complete response (CR) were assessed based on the 2009 revised New Solid Tumor Efficacy Evaluation Criteria, RECIST (version 1.1)[11]. The disease control rate (DCR) was calculated as the SD rate + PR rate + CR rate. The objective response rate (ORR) was calculated as the PR rate + CR rate. Two physicians conducted all assessments; (2) Serum tumor markers: The levels of carbohydrate antigen (CA) 19-9, CA125, and carcinoembryonic antigen (CEA) were measured in both patient groups before (prior to the first treatment) and after treatment (prior to the third treatment) for evaluation; (3) Immune function: The numbers of CD3+, CD4+, CD4+/CD8+, and natural killer (NK) cells were assessed in both groups before (prior to the first treatment) and after (prior to the third treatment) treatment; and (4) Safety evaluation: Adverse events were graded and documented according to the Common Terminology Criteria for Adverse Events of the United States National Cancer Institute. Adverse reactions were classified as grades I-IV. The primary observations focused on the incidence of grade I-IV adverse reactions during treatment in both groups, including myelosuppression and hepatorenal impairment.

Statistical analysis

Data were analyzed and visualized using Statistical Package for the Social Sciences 26.0 and R 4.3.3 statistical software. Quantitative data are presented as the mean ± SD for normally distributed data, and non-normally distributed data are presented as medians with interquartile ranges. Survival analysis was performed using the Kaplan-Meier method to estimate the median survival time (MST) and median modified PFS (mPFS), reported in months, with a 95%CI. Statistical significance was set at P < 0.05.

RESULTS

Long-term efficacy

The MST of the 136 patients was 12.32 months (95%CI: 11.06-13.58). The 9-month, 12-month, 15-month, and 18-month survival rates were 82.9%, 54.6%, 26.7%, and 13.4%, respectively. The MST for patients in the ICWM group was 12.91 months (95%CI: 12.10-13.72), while that in the WM group was 10.64 months (95%CI: 9.41-11.87). The 9-month, 12-month, 15-month, and 18-month survival rates were 90.8%, 59.2%, 32.9%, and 16.4% in the ICWM group and 74.1%, 42.2%, 20.3%, and 8.5% in the WM group, respectively. The MST was significantly longer in the ICWM group than that in the WM group (P < 0.05; Figure 1).

Figure 1 Survival comparison of patients. A: Survival comparison of the 136 patients with advanced pancreatic cancer; B: Survival comparison between the integration of Chinese and Western medicine and Western medicine groups. ICWM: Integration of Chinese and Western medicine; WM: Western medicine.

The median mPFS of the 136 patients was 4.43 months (95%CI: 3.38-5.28). Specifically, the mPFS for patients in the ICWM group was 5.12 months (95%CI: 4.74-5.50), while that for patients in the WM group was 3.55 months (95%CI: 3.07-4.03). The mPFS was significantly longer in the ICWM group than in the WM group (P < 0.05; Figure 2).

Figure 2 Modified progression-free survival of patients. A: Modified progression-free survival of the 136 patients with advanced pancreatic cancer; B: Modified progression-free survival of patients in the integration of Chinese and Western medicine and Western medicine groups. ICWM: Integration of Chinese and Western medicine; WM: Western medicine.

Short-term efficacy

Efficacy in solid tumors: The DCR rate in the ICWM group was 62 patients, accounting for 96.9% of the total number of patients in the ICWM group. In the WM group, the DCR rate was 58 patients, representing 82.5% of the total number of patients in the WM group. The DCR rate was significantly higher in the ICWM group than in the WM group (P < 0.05). The PR, progressive disease, or ORR did not differ significantly between the two groups (Table 2).

Table 2 Comparison of the short-term efficacy in 136 cases of advanced pancreatic cancer, n (%).

Group	Complete response	Partial response	Stable disease	Progressive disease	Disease control rate	Objective response rate
Integration of Chinese and Western medicine group (n = 66)	0 (0.0)	14 (21.2)	48 (72.7)	4 (6.1)	62 (93.9)a	14 (21.2)
Western medicine group (n = 70)	0 (0.0)	15 (21.4)	45 (63.3)	10 (14.3)	58 (82.9)	15 (21.4)

^aP < 0.05 indicates a significant difference in intergroup comparison.

Comparison of tumor markers before and after treatment in both groups

The serum tumor markers CA199 and CA125 showed a significant decrease in the ICWM group after treatment (P < 0.05). However, in the WM group, only the CA199 Levels decreased significantly vs the levels before treatment (P < 0.05). The CEA levels did not differ significantly between the two groups before and after treatment (P > 0.05; Table 3).

Table 3 Comparison of tumor markers before and after treatment in the two groups, median (interquartile ranges).

Group	Time	CA199 (U/mL)	CA125 (U/mL)	CEA (ng/mL)
Integration of Chinese and Western medicine group (n = 66)	Before treatment	853.31 (20.70, 8560.03)	55.90 (24.90, 252.70)	5.67 (2.59, 18.83)
	After treatment	317.95 (28.35, 5593.16)a	47.50 (16.80, 169.10)a	6.94 (3.40, 21.81)
Western medicine group (n = 70)	Before treatment	455.29 (55.77, 2722.84)	66.12 (23.67, 150.46)	6.16 (3.30, 24.10)
	After treatment	628.21 (42.18, 1902.00)a	67.65 (20.43, 200.30)	8.81 (4.08, 28.38)

^aP < 0.05 indicates a significant difference in intragroup comparison.

CA: Carbohydrate antigen; CEA: Carcinoembryonic antigen.

Comparison of immune function

Both the ICWM and WM groups exhibited an upward trend in NK cells and CD3+, CD4+, and CD4+/CD8+ lymphocytes after treatment vs before treatment (P < 0.05). However, the immune parameters in the ICWM group showed a more pronounced increase after treatment than those in the WM group (P < 0.05; Table 4).

Table 4 Comparison of immune function between the two groups before and after treatment, mean ± SD.

Group	Time	CD3+ (%)	CD4+ (%)	CD4+/CD8+	NK (%)
Integration of Chinese and Western medicine group (n = 66)	Before treatment	58.02 ± 4.48	35.01 ± 3.81	1.14 ± 0.13	5.85 ± 1.57a
	After treatment	69.98 ± 8.01a,b	45.02 ± 3.47a,b	1.83 ± 0.79a,b	17.44 ± 3.68a,b
Western medicine group (n = 70)	Before treatment	58.71 ± 3.45	36.31 ± 3.84	1.17 ± 0.97	7.85 ± 0.97
	After treatment	64.07 ± 4.47a	38.95 ± 4.57a	1.48 ± 0.11a	14.94 ± 0.43a

^aP < 0.05, for intragroup comparisons.

^bP < 0.05, for intergroup comparisons.

NK: Natural killer.

Safety comparison

The incidences of grade II and III myelosuppression in the ICWM group were 14 cases and 6 cases vs 21 patients and 12 patients in the WM group; these represented 21.7% and 9.1% of the total in the ICWM group vs 30.0% and 17.1% in the WM group, respectively, showing statistically significant differences (P < 0.05). However, no significant differences were observed in hepatic or renal function impairment between the two groups (P > 0.05; Table 5).

Table 5 Comparison of safety outcomes between the two groups, n (%).

Group	Myelosuppression				Hepatic impairment				Renal impairment
	Grade I	Grade II	Grade III	Grade IV	Grade I	Grade II	Grade III	Grade IV	Grade I	Grade II	Grade III	Grade IV
Integration of Chinese and Western medicine group (n = 66)	30	14	6	1	12	5	7	1	2	1	0	0
Western medicine group (n = 70)	30	21	12	3	12	5	8	0	1	1	0	0
P value	0.003				0.890						0.631

DISCUSSION

In this study, we analyzed the clinical data of patients with advanced PC treated at Henan Provincial Hospital of Traditional Chinese Medicine and Henan Provincial People’s Hospital between January 2019 and December 2024. Patients were divided into the ICWM and WM groups according to the treatment modality. The MST was 12.91 months for the ICWM group compared with 10.64 months in WM group. A systematic review and network meta-analysis involving 79 studies, 72 treatment regimens, and 222104 patients reported no MST exceeding 12 months in patients with advanced PC[12]. In contrast, the present study demonstrated that the ICWM group surpassed this threshold, approaching the survival outcomes achieved in a recent phase II clinical trial of a targeted-immunotherapy-based regimen (MST: 13.7 months with panitumumab, anlotinib, and albumin-bound paclitaxel/gemcitabine)[13]. The WM group in this study achieved survival outcomes near the upper range of current regimens, the ICWM group extended survival by approximately 2.24 months. A meta-analysis of 29 randomized controlled trials that included 1808 patients with unresectable advanced PC demonstrated that the combination of TCM prescriptions and conventional therapy significantly improved the 1-year survival rate[14]. These findings suggest that integrated treatment may provide a clinically meaningful breakthrough while offering advantages in terms of cost and accessibility compared with targeted immunotherapy strategies. Notably, after 35 months, no patient in the WM group survived, whereas two patients in the ICWM group survived for more than 50 months, highlighting the potential for long-term survival benefits with integrated therapy. The mPFS was 5.12 months in the ICWM group vs 3.55 months in the WM group, which is consistent with the ranges reported in previous studies[15-17]. The limited PFS may reflect the high invasiveness and heterogeneity of PC, as well as mechanisms such as neurofibrillary invasion within the tumor microenvironment[18,19]. Meanwhile, the dissociation between PFS and OS observed in ICWM may represent a manifestation of the dialectical relationship between tumor “local control” and “OS”. TCM may contribute to prolonged OS without significantly delaying tumor progression through multiple mechanisms, including toxicity management, immunomodulation, and preservation of host function. This phenomenon further underscores the necessity of moving beyond a tumor shrinkage-centric evaluation paradigm toward a more comprehensive, multi-dimensional framework to assess the efficacy of integrated traditional Chinese and WM in oncology.

In terms of tumor response, the ORR did not differ significantly between the two groups. However, the DCR in the ICWM group was significantly higher, exceeding that reported for modified FOLFIRINOX (86.5%) and nab-paclitaxel plus gemcitabine (82.4%)[20,21]. These findings suggest that TCM contributes to the stabilization of local diseases. Among the tumor markers, serum CA19-9, CA125, and CEA levels remain important prognostic indicators in PC. A CA19-9 reduction is typically associated with a decreased tumor burden[22], while elevated CA125 Levels are often linked to metastasis and peritoneal involvement. In this study, only CA19-9 levels decreased significantly in the WM group, whereas both CA19-9 and CA125 levels declined in the ICWM group, suggesting a broader biomarker improvement with integrated therapy[23]. Inhibition of the IL-6/JAK/STAT3 signaling pathway has been identified as a mechanism by which Chinese herbal medicines suppress malignant ascites formation[24]. Immune function analysis showed increases in CD3+ lymphocytes, CD4+ lymphocytes, CD4+/CD8+ ratio, and NK cells after treatment in both groups, with greater improvements in the ICWM group. These results align with prior evidence that Chinese herbal medicines enhance anti-tumor immunity by modulating NK cells, dendritic cells, and T lymphocytes, acupuncture promotes tumor immunity in mouse models via CD5⁺ dendritic cell and T-cell mediated mechanisms[25]; likewise, astragalus polysaccharides promote dendritic cell maturation by upregulating CD80 and CD86 expression[26]. These studies provide mechanistic support for the TCM principle of “Fuzheng”[27].

Safety evaluations demonstrated that hepatic and renal function impairments did not differ significantly between the groups. However, the incidence of grade II and III myelosuppression was significantly lower in the ICWM group, indicating the protective effect of TCM against chemotherapy-related hematological toxicity. These findings highlight the favorable safety profile of integrated therapies.

Guided by the core TCM principles of a holistic perspective and treatment based on syndrome differentiation, the integrated therapy used in this study employed a systematic and standardized approach. Unlike single-modality TCM treatments, this involves the dynamic adjustment of the therapeutic regimen in accordance with the progression of the patient’s condition and their constitutional changes. Unlike WM alone, it leverages multidimensional TCM participation across the entire treatment process, complementing modern medicine. Collectively, this study suggests that ICWM can prolong survival, control local disease, reduce tumor markers, enhance immune function, and improve both short-term and long-term efficacy, while maintaining safety.

This study has several limitations inherent to its dual-center retrospective cohort design. First, selection bias could have been introduced because of patient preferences in choosing a healthcare facility. Second, heterogeneity in treatment details exists between centers, and center effects may arise from variations in instrument calibration standards and clinical follow-up procedures. Third, the retrospective nature of the study precludes complete control for unmeasured confounding factors, and the relatively small sample size may limit the statistical power. Nevertheless, both hospitals included in this study are tertiary A-class hospitals in China, characterized by a high degree of standardization in diagnostic and therapeutic technologies. Furthermore, no statistically significant differences were observed in baseline characteristics between the two groups, which helped mitigate potential bias and enhance the reliability of the findings. Future research should involve randomized controlled trials with larger multicenter cohorts to further investigate and validate the efficacy and safety of ICWM in treating advanced PC, thereby providing higher-level evidence for clinical practice.

CONCLUSION

ICWM constitutes an effective and safe strategy for treating advanced PC, as evidenced by prolonged OS, improved local tumor control, reduced serum tumor markers, and enhanced immunological function.