Introduction
Lung cancer remains a major global health burden, with approximately 2.5 million new cases worldwide in 2022 [1]. Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases, with adenocarcinoma being the predominant histopathological subtype [2]. Lung cancer development is associated with multiple factors, particularly tobacco exposure, as well as environmental and genetic factors [3] Genetic polymorphisms, including variants of CYP2A6 and CYP2A13, have also been associated with lung cancer risk among Indonesian female never-smokers exposed to environmental tobacco smoke [4].
Chemotherapy remains an important systemic treatment for patients with advanced NSCLC, but it is frequently associated with hematological and non-hematological toxicities that may adversely affect quality of life and treatment continuity [5]. Chemotherapy may also influence antitumor immunity. CD8+ T cells play a central role in cellular antitumor immune responses through their ability to recognize and eliminate malignant cells, making the preservation of CD8+ T-cell function relevant during systemic treatment [6].
Supportive nutritional and immunomodulatory approaches have therefore been explored to mitigate treatment-related toxicities and preserve immune function. Curcumin, a major bioactive component of Curcuma longa, has antioxidant, anti-inflammatory, and immunomodulatory properties and has been extensively investigated for its potential role in cancer prevention and treatment [7]. Fatty acids may also influence immune responses and have been investigated for their potential immunomodulatory roles in cancer [8]. More broadly, immunonutritional support may contribute to maintaining nutritional and immune status during cancer treatment [9].
Channa striata extract contains protein and other nutritional components that may provide supportive benefits during systemic treatment. The nutritional properties of Channa striata and the anti-inflammatory, antioxidant, and immunomodulatory properties of Curcuma provide a rationale for investigating their combined use as supportive therapy. However, evidence regarding the combined effects of Curcuma and Channa striata extract supplementation on CD8+ T-cell levels and chemotherapy-related toxicities in patients with NSCLC remains limited, particularly in Indonesia.
Therefore, this study aimed to evaluate the effects of combined Curcuma and Channa striata extract supplementation on CD8+ T-cell levels and hematological and non-hematological toxicities in patients with NSCLC undergoing two cycles of chemotherapy.
Methods
Study Design and Setting
This prospective, double-blind, randomized controlled trial included patients with NSCLC undergoing chemotherapy at Prof. Dr. Chairuddin P. Lubis Universitas Sumatera Utara Hospital, Medan, and affiliated hospitals, including Murni Teguh Memorial Hospital and Elisabeth Hospital. Participants were randomly assigned in a 1:1 ratio to receive either combined Curcuma and Channa striata extract supplementation (Striatamin®) or placebo during two chemotherapy cycles.
Participants and Eligibility Criteria
Eligible participants were patients aged 30–70 years with cytologically and/or histopathologically confirmed NSCLC, an Eastern Cooperative Oncology Group (ECOG) performance status of 0–3, and a plan to undergo at least two cycles of systemic chemotherapy. All participants provided written informed consent and agreed to receive the assigned supplementation throughout the two-cycle intervention period.
Patients were excluded if they had severe active inflammatory conditions, including sepsis or active pneumonia; active tuberculosis, HIV/AIDS, or uncontrolled diabetes mellitus; a known allergy to Curcuma, Channa striata, or fish-derived products; concurrent use of other immunomodulatory supplements; or inability to complete two chemotherapy cycles.
Sample Size
The minimum required sample size was 25 participants per group, calculated using a 95% confidence level and 80% statistical power based on expected variability in CD8+ T-cell levels. To account for an anticipated dropout rate of 10%, the planned sample size was increased to approximately 28 participants per group.
Randomization and Blinding
Block randomization with a block size of four was generated using Research Randomizer. Participants were allocated to the intervention or placebo group in a 1:1 ratio. Allocation was managed by an independent researcher who was not involved in clinical assessment or data analysis.
Striatamin® and placebo capsules were identical in color, size, texture, and appearance to maintain blinding of both participants and clinical investigators. Allocation codes remained concealed until completion of primary data collection and the initial statistical analysis.
Intervention
Participants in the intervention group received Striatamin®, a nutraceutical preparation containing Curcuma longa (curcumin) extract and Channa striata extract. The supplement was administered at a dose of two capsules three times daily (six capsules per day) during two chemotherapy cycles. Participants in the control group received placebo capsules that were identical in appearance, size, color, and administration schedule but contained no active ingredients. All participants continued to receive standard chemotherapy according to institutional treatment protocols. Adherence to the assigned supplementation was assessed through capsule counts and participant interviews during follow-up visits.
Outcome Assessment
CD8+ T-cell levels and chemotherapy-related hematological and non-hematological toxicities were assessed before the first chemotherapy cycle and after the second cycle. CD8+ T-cell levels were measured using an enzyme-linked immunosorbent assay (ELISA) and expressed in ng/mL.
Hematological assessments included hemoglobin level, absolute neutrophil count (ANC), and platelet count. Hematological and non-hematological toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
Statistical Analysis
Data were analyzed using the Statistical Package for the Social Sciences (SPSS). Continuous variables were summarized as mean ± standard deviation or median (range), according to their distribution, whereas categorical variables were presented as frequencies and percentages. Data distribution was assessed using the Shapiro–Wilk test.
Between-group and within-group statistical tests were selected according to data distribution and variable type, as specified in the table notes. All statistical tests were two-sided, and a p-value <0.05 was considered statistically significant.
Ethical Considerations
The study protocol was approved by the Health Research Ethics Committee of the Faculty of Medicine, Universitas Sumatera Utara, Medan (No. 61/KEPK/USU/2026) before participant recruitment and data collection. All participants received information regarding the study objectives, procedures, potential benefits, and risks and provided written informed consent before enrollment. Participant confidentiality was maintained throughout the study.
Results
Characteristics of the Study Participants
Fifty patients completed the study, with 25 participants in each group. Baseline demographic and clinical characteristics were comparable between the Striatamin® and control groups (all p > 0.05). Most participants were male, were heavy smokers, had adenocarcinoma, had stage IV disease, and had an ECOG performance status of 1 (Table 1).
| Characteristic | Striatamin® (n=25) | Control (n=25) | p-value |
| Sex, n (%) | 1.000ᵃ | ||
| Male | 22 (88) | 22 (88) | |
| Female | 3 (12) | 3 (12) | |
| Age, years, mean ± SD | 54.76 ± 8.00 | 56.28 ± 5.90 | 0.501ᵇ |
| Smoking status, n (%) | 0.297 | ||
| Passive smoker | 1 (4) | 2 (8) | |
| Light smoker | 3 (12) | 0 | |
| Moderate smoker | 3 (12) | 2 (8) | |
| Heavy smoker | 18 (72) | 21 (84) | |
| Histopathology, n (%) | 0.314 | ||
| Adenocarcinoma | 16 (64) | 13 (52) | |
| Squamous cell carcinoma | 7 (28) | 12 (48) | |
| Large-cell carcinoma | 2 (8) | 0 | |
| Stage, n (%) | 0.737ᶜ | ||
| IIIB | 2 (8) | 3 (12) | |
| IIIC | 3 (12) | 1 (4) | |
| IVA | 15 (60) | 16 (64) | |
| IVB | 5 (20) | 5 (20) | |
| ECOG performance status, n (%) | 0.747ᵈ | ||
| PS 1 | 19 (76) | 18 (72) | |
| PS 2 | 6 (24) | 7 (28) |
ᵃFisher’s exact test; ᵇMann–Whitney U test; ᶜKruskal–Wallis test; ᵈChi-square test.
Changes in CD8+ T-Cell Levels
CD8+ T-cell levels did not differ significantly between the groups at baseline (p = 0.734) or after two chemotherapy cycles (p = 0.367). Similarly, the change in CD8+ T-cell levels from baseline to post-cycle II did not differ significantly between the Striatamin® and control groups (p = 0.823). No significant within-group changes were observed in either the Striatamin® (p = 0.819) or control group (p = 0.493) (Table 2).
| CD8+ (ng/mL) | Striatamin® (n=25) | Control (n=25) | Between-group p |
| Pre-cycle I | 111.32 ± 48.7 | 103 (57.5–256) | 0.734 |
| Post-cycle II | 105 (40.8–234) | 95.5 (40–256) | 0.367 |
| Gain score | 2.03 ± 38.48 | −6.2 (−95–78.7) | 0.823 |
| Within-group p | 0.819 | 0.493 | — |
Note: Between-group comparisons were performed using the Mann–Whitney U test, and within-group comparisons were performed using the Wilcoxon signed-rank test. Normally distributed data are presented as mean ± SD, whereas non-normally distributed data are presented as median (range).
Hematological Toxicity
No significant between-group differences in hemoglobin, absolute neutrophil count (ANC), or platelet toxicity grades were observed either at baseline or after two chemotherapy cycles (all p > 0.05). Within the Striatamin® group, anemia severity increased significantly from baseline to post-cycle II (p = 0.009), whereas no significant within-group changes were observed in ANC or platelet toxicity. In the control group, no significant within-group changes were observed in hemoglobin, ANC, or platelet toxicity (Table 3).
| Variable/category | Striatamin® Pre | Striatamin® Post | Control Pre | Control Post |
| Hemoglobin | ||||
| Grade 0 | 1 (4) | 0 | 0 | 0 |
| Grade 1 | 9 (36) | 1 (4) | 6 (24) | 3 (12) |
| Grade 2 | 7 (28) | 10 (40) | 11 (44) | 7 (28) |
| Grade 3 | 8 (32) | 14 (56) | 8 (32) | 15 (60) |
| Between-group p | 0.448 | 0.982 | — | — |
| Within-group p | 0.009 | — | 0.114 | — |
| ANC | ||||
| Grade 0 | 25 (100) | 24 (96) | 24 (96) | 25 (100) |
| Grade 1 | 0 | 1 (4) | 1 (4) | 0 |
| Between-group p | 1.000 | 1.000 | — | — |
| Within-group p | 1.000 | — | 1.000 | — |
| Platelets | ||||
| Grade 0 | 25 (100) | 22 (88) | 23 (92) | 21 (84) |
| Grade 1 | 0 | 3 (12) | 1 (4) | 4 (16) |
| Grade 2 | 0 | 0 | 1 (4) | 0 |
| Between-group p | 0.153 | 1.000 | — | — |
| Within-group p | 0.250 | — | 0.705 | — |
Note: Data are presented as n (%). Between-group comparisons were performed using the Mann–Whitney U test or Fisher’s exact test, as appropriate. Within-group comparisons were performed using the marginal homogeneity test or McNemar’s test, as appropriate.
Non-Hematological Toxicity
Non-hematological toxicities increased significantly from pre-cycle I to post-cycle II in both groups (all within-group p<0.001). However, no significant between-group differences were observed after cycle II in nausea/vomiting, weight loss, alopecia, skin changes, sore throat, or nail disorders (all p>0.05). Most events were Grade 1–2; Grade 3 toxicity was observed only for nausea/vomiting, and no Grade 4 toxicity was observed (Table 4).
| Toxicity / category | Striatamin® Pre | Striatamin® Post | Within-group p | Control Pre | Control Post | Within-group p | Between-group Post p |
| Nausea/vomiting | <0.001 | <0.001 | 0.933 | ||||
| Grade 0 | 25 (100) | 0 | 24 (96) | 0 | |||
| Grade 1 | 0 | 4 (16) | 0 | 5 (20) | |||
| Grade 2 | 0 | 17 (68) | 0 | 16 (64) | |||
| Grade 3 | 0 | 4 (16) | 1 (4) | 4 (16) | |||
| Weight loss | <0.001 | <0.001 | 0.247 | ||||
| Grade 0 | 25 (100) | 6 (24) | 24 (96) | 2 (8) | |||
| Grade ≥1 | 0 | 19 (76) | 1 (4) | 23 (92) | |||
| Alopecia | <0.001 | <0.001 | 0.346 | ||||
| Grade 0 | 25 (100) | 2 (8) | 24 (96) | 0 | |||
| Grade 1 | 0 | 11 (44) | 1 (4) | 13 (52) | |||
| Grade 2 | 0 | 12 (48) | 0 | 12 (48) | |||
| Skin changes | <0.001 | <0.001 | 0.208 | ||||
| Grade 0 | 25 (100) | 9 (36) | 25 (100) | 5 (20) | |||
| Grade 1 | 0 | 16 (64) | 0 | 20 (80) | |||
| Sore throat | <0.001 | <0.001 | 1.000 | ||||
| Grade 0 | 25 (100) | 5 (20) | 25 (100) | 5 (20) | |||
| Grade 1 | 0 | 20 (80) | 0 | 20 (80) | |||
| Damaged nails | <0.001 | <0.001 | 0.762 | ||||
| Grade 0 | 25 (100) | 7 (28) | 25 (100) | 9 (36) | |||
| Grade 1 | 0 | 18 (72) | 0 | 16 (64) |
Note: Data are presented as n (%). Within-group comparisons were performed using the marginal homogeneity test or McNemar’s test, as appropriate. Between-group comparisons were performed using Fisher’s exact test, the Kruskal–Wallis test, or the chi-square test, as appropriate.
Discussion
Effect of Curcuma and Channa striata Extract Supplementation on CD8+ T-Cell Levels
This study showed that combined Curcuma and Channa striata extract supplementation was not associated with a significant increase in CD8+ T-cell levels compared with placebo after two cycles of chemotherapy. CD8+ T cells play a central role in antitumor cellular immunity,[6] although systemic anticancer therapy may exert complex effects on immune responses. Chemotherapy can promote antitumor immunity through mechanisms such as immunogenic cell death while simultaneously affecting immune-cell populations and function [10].
Curcumin has multiple biological activities relevant to cancer, including modulation of inflammatory and molecular signaling pathways [7]. Its potential role in lung cancer has also been associated with regulation of pathways involved in tumor proliferation, survival, apoptosis, and inflammatory responses [11]. In addition, Channa striata extract may provide nutritional support during chemotherapy. A randomized controlled study in patients with acute myeloid leukemia evaluated the effects of Channa striata extract supplementation on febrile neutropenia during chemotherapy, providing preliminary clinical evidence for its potential supportive role in patients receiving cytotoxic treatment [12] However, these potential biological and nutritional effects did not translate into a significant increase in peripheral CD8+ T-cell levels in the present study.
Curcumin has also been investigated for its potential protective effects against chemotherapy-induced adverse effects through antioxidant and anti-inflammatory mechanisms [13] Nevertheless, the absence of a significant effect on CD8+ T-cell levels in this study could reflect several factors, including the predominance of advanced-stage disease and the relatively short intervention period of two chemotherapy cycles. Furthermore, peripheral CD8+ T-cell concentration alone may not fully reflect antitumor immune function. Future studies incorporating functional immune markers, inflammatory biomarkers, and longer follow-up may provide a more comprehensive assessment of the immunomodulatory effects of supplementation.
Effect of Curcuma and Channa striata Extract Supplementation on Hematological Toxicity
No significant between-group differences in hematological toxicity were observed after two chemotherapy cycles. Anemia severity increased significantly within the Striatamin® group (p = 0.009), whereas the corresponding change in the control group was not statistically significant (p = 0.114). However, anemia severity did not differ significantly between the groups after cycle II (p = 0.982). No significant within- or between-group differences were observed for ANC or platelet toxicity.
Chemotherapy-related hematological toxicity may be influenced by cytotoxic effects on hematopoietic cells, disease burden, systemic inflammation, and nutritional status. Adequate nutritional assessment and support are therefore important components of cancer care, particularly during systemic anticancer treatment [14] Curcumin has been investigated for its potential protective effects against chemotherapy-related adverse effects,[13] and experimental evidence suggests that it may act through several molecular pathways relevant to lung cancer biology [15]. Similarly, the nutritional components of Channa striata could provide nutritional support during chemotherapy, although evidence regarding its effects on hematological toxicity remains limited [12].
The significant within-group increase in anemia severity in the Striatamin® group should be interpreted cautiously because the post-cycle II comparison between groups was not statistically significant. Therefore, this finding alone does not indicate that supplementation increased the risk of anemia. Rather, the overall results indicate that supplementation was not associated with a measurable protective effect against hematological toxicity during the two-cycle observation period.
Effect of Curcuma and Channa striata Extract Supplementation on Non-Hematological Toxicity
Non-hematological toxicities, including nausea/vomiting, weight loss, alopecia, skin changes, sore throat, and nail disorders, increased significantly from baseline to post-cycle II in both groups (all within-group p < 0.001). However, no significant between-group differences were observed after two chemotherapy cycles (all p > 0.05). Most events were Grade 1-2, Grade 3 toxicity was observed only for nausea/vomiting, and no Grade 4 toxicity was observed.
These findings are consistent with the recognized adverse effects of chemotherapy reported in patients with NSCLC [5]. Although curcumin has been proposed to mitigate chemotherapy-induced adverse effects through antioxidant and anti-inflammatory mechanisms,[13] supplementation was not associated with significantly lower non-hematological toxicity in the supplementation group.
Weight loss during chemotherapy is particularly relevant in patients with advanced cancer because it may reflect reduced nutritional intake, treatment-related adverse effects, and cancer-associated cachexia. Cancer cachexia is a multifactorial syndrome characterized by progressive loss of skeletal muscle mass and metabolic abnormalities that cannot be fully reversed by conventional nutritional support [16]. Clinical nutrition guidelines therefore emphasize early identification and management of nutritional problems in patients with cancer [17]. A later review also highlights the complex interaction among tumor-derived factors, systemic inflammation, metabolic alterations, and muscle wasting in cancer-associated cachexia [18].
Beyond general nutritional support, immunonutrition has been investigated as a strategy to influence immune and inflammatory responses in patients receiving cancer treatment. A systematic review of randomized controlled trials examined the effects of enteral immunonutrition on infectious complications and immune and inflammatory markers in patients undergoing chemotherapy [19]. However, the effects of specific nutritional interventions may vary with the formulation, patient population, disease status, and duration of treatment. Similarly, although curcumin has been extensively investigated in cancer, evidence regarding its clinical utility remains heterogeneous, emphasizing the need for appropriately designed clinical trials [20].
Overall, combined Curcuma and Channa striata extract supplementation did not significantly improve CD8+ T-cell levels or reduce hematological or non-hematological toxicities compared with placebo during two cycles of chemotherapy. The relatively small sample size and short intervention period may have limited the power to detect potential effects. Further studies with larger sample sizes, longer intervention periods, and more comprehensive assessments of nutritional status, inflammatory biomarkers, oxidative stress, and functional immune responses are warranted.
Conclusion
Combined Curcuma and Channa striata extract supplementation during two cycles of chemotherapy did not significantly increase CD8+ T-cell levels or reduce hematological and non-hematological toxicities compared with placebo in patients with NSCLC. Although anemia severity increased significantly within the Striatamin® group, there was no significant between-group difference after the second chemotherapy cycle. The study population was predominantly male, with a history of heavy smoking, adenocarcinoma histology, advanced-stage disease, and an ECOG performance status of 1.
These findings indicate that combined Curcuma and Channa striata extract supplementation did not show a statistically significant effect on the evaluated immunological and chemotherapy-related toxicity outcomes during the two-cycle study period.
Declarations
Acknowledgments
The authors thank all patients who participated in this study and the staff of the Thoracic Oncology Division and Clinical Pathology Laboratory for their assistance with patient recruitment, specimen collection, and laboratory analyses. The authors also acknowledge the Faculty of Medicine, Universitas Sumatera Utara; Prof. Dr. Chairuddin P. Lubis Universitas Sumatera Utara Hospital; and the affiliated hospitals for facilitating this research.
Funding
This research received no external funding.
Conflict of Interest
The authors declare no conflicts of interest.
Author Contributions
Conceptualization: Rahmat Hidayat, Setia Putra Tarigan, Dina Octafrida
Methodology: Rahmat Hidayat, Setia Putra Tarigan, Dina Octafrida
Investigation: Rahmat Hidayat, Setia Putra Tarigan, Dina Octafrida
Data Curation: Rahmat Hidayat
Formal Analysis: Rahmat Hidayat
Writing – Original Draft Preparation: Rahmat Hidayat
Writing – Review and Editing: Setia Putra Tarigan, Dina Octafrida, Noni Novisari Soeroso, Laksmi Wulandari, Elizabeth Napitupulu
Supervision: Setia Putra Tarigan, Dina Octafrida
All authors have read and approved the final version of the manuscript.
Informed Consent
Written informed consent was obtained from all participants before enrollment in the study.
Data Availability Statement
The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.