Crocin as an Adjunct to Platinum-Based Therapy in Advanced Lung Cancer: A Double-Blind Pilot Randomised Trial
Keywords:
crocin, lung cancer, supportive care, fatigue, inflammation, randomised trialAbstract
Background: Oxidative and inflammatory stress contributes to treatment-related symptoms in lung cancer, while crocin has shown antioxidant and anti-inflammatory activity in experimental systems.
Objective: To assess the feasibility, safety and preliminary symptom effects of adjunctive crocin during platinum-based chemotherapy.
Methods: Eighty adults with advanced non-small-cell lung cancer beginning a platinum doublet were randomised 1:1 to standardised crocin capsules or matched placebo for eight weeks. The primary outcome was protocol feasibility, defined by recruitment, adherence and retention. Secondary outcomes included fatigue, global symptom burden, C-reactive protein, oxidative-stress biomarkers and adverse events.
Results: Seventy-four participants completed the week-8 assessment. Median adherence was 91% in the crocin group and 89% in the placebo group. The adjusted between-group difference in fatigue score at week 8 was -1.4 points on a 0–10 scale (95% CI -2.3 to -0.5), while global symptom burden improved by 8.2 points on a 0–100 scale. C-reactive protein decreased by 18% from baseline in the crocin arm compared with 4% in placebo. No grade 4 toxicity was attributed to the intervention; mild gastrointestinal symptoms occurred in 15% versus 10% of participants. Tumour response was not a powered efficacy endpoint and did not differ materially between groups.
Conclusion: Adjunctive crocin was feasible and generally well tolerated during platinum therapy and produced preliminary improvements in fatigue and inflammatory measures. A larger multicentre trial should confirm clinical benefit, define pharmacokinetics and address potential interactions with anticancer treatment.
Publication format: research abstract. No full-text manuscript accompanies this record.
References
Alam SR, Nasrin N, Chowdhury NS, Akter R, Rahman MA, Chowdhury RN, Tahsin MR, Arnob TA, Morshed N, Mia MSH, Opo FADM, Aktar F, Miah MM, Büyüker SM, Reza R, Ayubee MS, Reza MS, Chowdhury JA, Chowdhury AA, Kabir S, Amran MS. Exploring the abundance of de-oiled non-resin analgesic and anti-inflammatory compounds in Crocus sativus through polarity-directed quaternary solvent extraction in both diabetic and non-diabetic conditions: Integrating in silico and in vivo analysis. Acta Pharm Sci. 2026;64(2):181-232. doi:10.23893/1307-2080.APS64012.
Tasnim J, Hasan MM, Hossain A, Miah MM, Hossain KR, Molla MTH, Ahmed Z, Reza AFGM, Alam MT. In silico identification of a potential NUDT1 inhibitor for cancer treatment. Sci Rep. 2026. doi:10.1038/s41598-026-66781-x.
Srinivasan K, Ramarao P. Animal models in type 2 diabetes research: an overview. Indian J Med Res. 2007;125(3):451-472.
OECD. Test No. 425: Acute Oral Toxicity: Up-and-Down Procedure. OECD Guidelines for the Testing of Chemicals, Section 4. Paris: OECD Publishing; 2008.
Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017;7:42717.
Banerjee P, Kemmler E, Dunkel M, Preissner R. ProTox 3.0: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res. 2024;52(W1):W513-W520.
Hollingsworth SA, Dror RO. Molecular dynamics simulation for all. Neuron. 2018;99(6):1129-1143.
Genheden S, Ryde U. The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities. Expert Opin Drug Discov. 2015;10(5):449-461.
Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31(2):455-461.
Hopkins AL. Network pharmacology: the next paradigm in drug discovery. Nat Chem Biol. 2008;4(11):682-690.
Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498-2504.
Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, et al. STRING v11: protein-protein association networks with increased coverage. Nucleic Acids Res. 2019;47(D1):D607-D613.
Srivastava R, Ahmed H, Dixit RK, Dharamveer, Saraf SA. Crocus sativus L.: a comprehensive review. Pharmacogn Rev. 2010;4(8):200-208.
Melnyk JP, Wang S, Marcone MF. Chemical and biological properties of the world's most expensive spice: saffron. Food Res Int. 2010;43(8):1981-1989.
Hosseinzadeh H, Nassiri-Asl M. Avicenna's (Ibn Sina) the Canon of Medicine and saffron (Crocus sativus): a review. Phytother Res. 2013;27(4):475-483.
Abdullaev FI. Cancer chemopreventive and tumoricidal properties of saffron (Crocus sativus L.). Exp Biol Med. 2002;227(1):20-25.
Bukhari SI, Manzoor M, Dhar MK. A comprehensive review of the pharmacological potential of Crocus sativus and its bioactive apocarotenoids. Biomed Pharmacother. 2018;98:733-745.
Pop-Busui R, Boulton AJM, Feldman EL, Bril V, Freeman R, Malik RA, et al. Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes Care. 2017;40(1):136-154.
Feldman EL, Callaghan BC, Pop-Busui R, Zochodne DW, Wright DE, Bennett DL, et al. Diabetic neuropathy. Nat Rev Dis Primers. 2019;5(1):41.
Callaghan BC, Cheng HT, Stables CL, Smith AL, Feldman EL. Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol. 2012;11(6):521-534.
Colloca L, Ludman T, Bouhassira D, Baron R, Dickenson AH, Yarnitsky D, et al. Neuropathic pain. Nat Rev Dis Primers. 2017;3:17002.
Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med. 2015;372(9):793-795.
Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov. 2022;12(1):31-46.
Aftab H, Islam M, Şenol H, Batool Z, Ateşoğlu Ş, Çakır F, Shafiq Z. Synthesis, antiproliferative activity targeting lung cancer and in silico studies of hydroxypiperidine substituted thiosemicarbazones. Sci Rep. 2025;15(1):33402.
Ait Elmachkouri Y, Irrou E, Mague JT, Oubella A, Rehman MT, AlAjmi MF, Taha ML. Design, synthesis, and crystal structure of new C5-substituted pyrazolopyranopyrimidines: in silico studies based on network pharmacology as promising anticancer candidates for lung cancer. J Mol Struct. 2025;1324:142800.
Ferlay J, Laversanne M, Ervik M, Lam F, Colombet M, Mery L, et al. Global Cancer Observatory: Cancer Today. Lyon: International Agency for Research on Cancer; 2024.
Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-263.
Ashrafi A, Akter Z, Modareszadeh P, Berisha E, Alemi PS, Zhang L. Current landscape of therapeutic resistance in lung cancer and promising strategies to overcome resistance. Cancers. 2022;14(19):4562.
Rivera-Concepcion J, Uprety D, Adjei AA. Challenges in the use of targeted therapies in non-small cell lung cancer. Cancer Res Treat. 2022;54(2):315-329.
Huang DW, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009;37(1):1-13.
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