Skip to main content

Advertisement

SpringerLink
Log in

Comparison of quick recovery outcome of inhalable doxorubicin and cisplatin in lung cancer patients: a randomized, double-blind, single-center trial

  • Clinical Trial
  • Published:
Drug Delivery and Translational Research Aims and scope Submit manuscript

Abstract

Systematic chemotherapy has required high time span for recovery in cancer patients, serious toxic effects, and increased the time of cancer-free survival of patient but decreased the overall survival time of patients irrespective of diseased condition(s). To compare the quick recovery of inhalable doxorubicin and cisplatin in the lung cancer patients. A total of 240 patients with non-small cell lung cancer (NSCLC) patients were randomly divided into two groups of 120 each. Patients had inhaled 25 mg/m2 doxorubicin (DON group) or 10 mg/m2 cisplatin (CPN group) once in a day for 21 days. Volume, diameter, type, and a number of lung nodes, pulmonary function, and 21-day lung cancer risk assessment were evaluated. One-way ANOVA following Bonferroni multiple comparison tests was performed at 95% of confidence level. DON and CPN both groups had shrunken the lung cancer nodule, decreased solid nodules and non-solid nodules, and increased partially solid nodules. The DON group (5.88 ± 3.98%) had strongly decreased nodule size than the CPN group (4.15 ± 2.92%; p < 0.0001, q = 3.721). The incidence of nodular size reduction was 9.47 ± 1.13% higher for doxorubicin than cisplatin. The CPN group had 36.53 ± 0.66% and the DON group had 34.65 ± 0.7% lung cancer risk assessment after 21 days (p < 0.0001, q = 3.785). Inhalable doxorubicin might be an effective therapy in NSCLC patients with acceptable hematologic and non-hematologic toxic effects. Trial Registry: researchregistry3382, dated 28 December 2014 (www.researchregistry.com).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Rudokas M, Najlah M, Alhnan MA, Elhissi A. Liposome delivery systems for inhalation: a critical review highlighting formulation issues and anticancer applications. Med Princ Pract. 2016;25:60–72. https://doi.org/10.1159/000445116.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Yang LL, Zhang XC, Yang XN, Yang JJ, Wang Z, Chen HJ, et al. Lung cancer treatment disparities in China: a question in need of an answer. Oncologist. 2014;19:1084–90. https://doi.org/10.1634/theoncologist.2014-0007.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Takanen S, Bangrazi C, Graziano V, Parisi A, Resuli B, Simione L, et al. Number of mediastinal lymph nodes as a prognostic factor in PN2 non-small cell lung cancer: a single centre experience and review of the literature. Asian Pac J Cancer Prev. 2014;15:7559–62. https://doi.org/10.7314/APJCP.2014.15.18.7559.

    Article  PubMed  Google Scholar 

  4. Zhang X, Lu S, Zhang L, Liao M, Wang C, Cheng Y, et al. Guideline for diagnosis and treatment of ALK-positive non-small cell lung cancer in China. Chinese J Pathol. 2015;44:696–703. [Article in Chinese]. https://doi.org/10.3760/cma.j.issn.0529-5807.2015.10.003.

    Article  Google Scholar 

  5. Barletta E, Federico P, Tinessa V, Germano D, Cannella L, Pironti T, et al. Long-term survival in a patient with metastatic squamous cell lung carcinoma: a case report. Mol Clin Oncol. 2017;7:928–30. https://doi.org/10.3892/mco.2017.1408.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Steuer CE, Behera M, Ernani V, Higgins KA, Saba NF, Shin DM, et al. Comparison of concurrent use of thoracic radiation with either carboplatin-paclitaxel or cisplatin-etoposide for patients with stage III non-small-cell lung cancer: a systematic review. JAMA Oncol. 2017;3:1120–9. https://doi.org/10.1001/jamaoncol.2016.4280.

    Article  PubMed  Google Scholar 

  7. Forde PM, Ettinger DS. Targeted therapy for non-small-cell lung cancer: past, present, and future. Expert Rev Anticancer Ther. 2013;13:745–58. https://doi.org/10.1586/era.13.47.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Xu J, Du Y, Liu XJ, Zhu BY, Zhang SH, Li L, et al. Recombinant EGFR/MMP-2 bi-targeted fusion protein markedly binding to non-small-cell lung carcinoma and exerting potent therapeutic efficacy. Pharmacol Res. 2017:66–76. https://doi.org/10.1016/j.phrs.2017.04.001.

  9. Schmid O, Jud C, Umehara Y, Mueller D, Bucholski A, Gruber F, et al. Biokinetics of aerosolized liposomal ciclosporin a in human lung cells in vitro using an air-liquid cell interface exposure system. J Aerosol Med Pulm Drug Deliv. 2017;30:411–24. https://doi.org/10.1089/jamp.2016.1361.

    Article  PubMed  CAS  Google Scholar 

  10. Otterson GA, Villalona-Calero MA, Hicks W, Pan X, Ellerton JA, Gettinger SN, et al. Phase I/II study of inhaled doxorubicin combined with platinum-based therapy for advanced non-small cell lung cancer. Clin Cancer Res. 2010;16:2466–73. https://doi.org/10.1158/1078-0432.CCR-09-3015.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Garbuzenko OB, Saad M, Betigeri S, Zhang M, Vetcher AA, Soldatenkov VA, et al. Intratracheal versus intravenous liposomal delivery of siRNA, antisense oligonucleotides, and anticancer drug. Pharm Res. 2009;26:382–94. https://doi.org/10.1007/s11095-008-9755-4.

    Article  PubMed  CAS  Google Scholar 

  12. Wittgen BP, Kunst PW, van der Born K, van Wijk AW, Perkins W, Pilkiewicz FG, et al. Phase I study of aerosolized SLIT cisplatin in the treatment of patients with carcinoma of the lung. Clin Cancer Res. 2007;13:2414–21. https://doi.org/10.1158/1078-0432.CCR-06-1480.

    Article  PubMed  CAS  Google Scholar 

  13. Otterson GA, Villalona-Calero MA, Sharma S, Kris MG, Imondi A, Gerber M, et al. Phase I study of inhaled doxorubicin for patients with metastatic tumors to the lungs. Clin Cancer Res. 2007;13:1246–52. https://doi.org/10.1158/1078-0432.CCR-06-1096.

    Article  PubMed  CAS  Google Scholar 

  14. Veronesi G, Szabo E, Decensi A, Guerrieri-Gonzaga A, Bellomi M, Radice D, et al. Randomized phase II trial of inhaled budesonide versus placebo in high-risk individuals with CT screen-detected lung nodules. Cancer Prev Res. 2011;4:34–42. https://doi.org/10.1158/1940-6207.

    Article  CAS  Google Scholar 

  15. Sawabata N, Nagayasu T, Kadota Y, Horio H, Mori T, Yamashita S, et al. Risk assessment of lung resection for lung cancer according to pulmonary function: republication of systematic review and proposals by guideline committee of the Japanese Association for chest surgery 2014. Gen Thorac Cardiovasc Surg. 2015;63:14–21. https://doi.org/10.1007/s11748-014-0475-x.

    Article  PubMed  Google Scholar 

  16. Hong W, Guo R, Chen J-L, Han E-H, Wu T. The implementation of the elastography score in combination with ultrasound prevents unnecessary biopsy of cardiac lesions. Biomed Pharmacother. 2018;97:395–401. https://doi.org/10.1016/j.biopha.2017.10.081.

    Article  PubMed  Google Scholar 

  17. Sun Z, Cheng X, Ge Y, Shao L, Xuan Y, Yan G. An application study of low-dose computed tomography perfusion imaging for evaluation of the efficacy of neoadjuvant chemotherapy for advanced gastric adenocarcinoma. Gastric Cancer. 2017; https://doi.org/10.1007/s10120-017-0763-0.

  18. Nokihara H, Lu S, Mok TS, Nakagawa K, Yamamoto N, Shi YK, et al. Randomized controlled trial of S-1 versus docetaxel in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy (East Asia S-1 Trial in Lung Cancer). Ann Oncol. 2017;28:2698–706. https://doi.org/10.1093/annonc/mdx419.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Mangal S, Gao W, Li T, Zhou QT. Pulmonary delivery of nanoparticle chemotherapy for the treatment of lung cancers: challenges and opportunities. Acta Pharmacol Sin. 2017;38:782–97. https://doi.org/10.1038/aps.2017.34.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Roa WH, Azarmi S, Al-Hallak MH, Finlay WH, Magliocco AM, Lobenberg R. Inhalable nanoparticles, a non-invasive approach to treat lung cancer in a mouse model. J Control Release. 2011;150:49–55. https://doi.org/10.1016/j.jconrel.2010.10.035.

    Article  PubMed  CAS  Google Scholar 

  21. Punia R, Raina K, Agarwal R, Singh RP. Acacetin enhances the therapeutic efficacy of doxorubicin in non-small-cell lung carcinoma cells. PLoS One. 2017;12:e0182870. https://doi.org/10.1371/journal.pone.0182870.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Sekine I, Harada H, Yamamoto N, Wakabayashi M, Murakami H, Goto K, et al. Randomized phase II trial of weekly dose-intensive chemotherapy or amrubicin plus cisplatin chemotherapy following induction chemoradiotherapy for limited-disease small cell lung cancer (JCOG1011). Lung Cancer. 2017;108:232–7. https://doi.org/10.1016/j.lungcan.2017.04.002.

    Article  PubMed  Google Scholar 

  23. Satouchi M, Kotani Y, Shibata T, Ando M, Nakagawa K, Yamamoto N, et al. Phase III study comparing amrubicin plus cisplatin with irinotecan plus cisplatin in the treatment of extensive-disease small-cell lung cancer: JCOG 0509. J Clin Oncol. 2014;32:1262–8. https://doi.org/10.1200/JCO.2013.53.5153.

    Article  PubMed  CAS  Google Scholar 

  24. Paken J, Govender CD, Sewram V. Research protocol: cisplatin-associated ototoxicity amongst patients receiving cancer chemotherapy and the feasibility of an audiological monitoring program. BMC Womens Health. 2017;17:129. https://doi.org/10.1186/s12905-017-0486-8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Wang A, Wang W, Chen Y, Ma F, Wei X, Bi Y. Deguelin induces PUMA-mediated apoptosis and promotes sensitivity of lung cancer cells (LCCs) to doxorubicin (Dox). Mol Cell Biochem. 2017;442:177–86. https://doi.org/10.1007/s11010-017-3202-y.

    Article  PubMed  CAS  Google Scholar 

  26. Wang BL, Shen YM, Zhang QW, Li YL, Luo M, Liu Z, et al. Codelivery of curcumin and doxorubicin by MPEG-PCL results in improved efficacy of systemically administered chemotherapy in mice with lung cancer. Int J Nanomedicine. 2013;8:3521–31. https://doi.org/10.2147/IJN.S45250.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Spreckelmeyer S, Estrada-Ortiz N, Prins GG, van der Zee M, Gammelgaard B, Sturup S, et al. On the toxicity and transport mechanisms of cisplatin in kidney tissues in comparison to a gold-based cytotoxic agent. Metallomics. 2017;9:1786–95. https://doi.org/10.1039/c7mt00271h.

    Article  PubMed  CAS  Google Scholar 

  28. Lee HJ, Goo JM, Lee CH, Park CM, Kim KG, Park EA, et al. Predictive CT findings of malignancy in ground-glass nodules on thin-section chest CT: the effects on radiologist performance. Eur Radiol. 2009;19:552–60. https://doi.org/10.1007/s00330-008-1188-2.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are thankful for medical, radiological, pathological, and non-medical staff of Jining Medical College Affiliated Hospital, Jining, China, who made this study successful.

Author information

Authors and Affiliations

  1. Department of Thoracic Surgery, Jining Medical College Affiliated Hospital, No. 77 Gukui Street, Jining, 272000, Shandong, China

    Zhen Li, Zhun He, Ling Zong, Bo Jiang, Tao Zhang & Zhiliang Hu

  2. Department of Endocrinology, Jining Medical College Affiliated Hospital, Jining, 272000, China

    Min Song

Authors
  1. Zhen Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Min Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhun He
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ling Zong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bo Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tao Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhiliang Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors have read and approved the manuscript. The study concept was of Zhen Li. Min Song had performed the study design. Zhun He had performed the data acquisition. Ling Zong had performed quality control of data and algorithms. Bo Jiang had carried out data analysis and interpretation. Tao Zhang had performed statistical analysis. Zhiliang Hu had written and edited the manuscript for intellectual content. All authors were agreed to be accountable for all aspects of work ensuring integrity and accuracy.

Corresponding author

Correspondence to Zhiliang Hu.

Ethics declarations

The study had been registered in research registry (www.researchregistry.com), UID No.: researchregistry3382, dated 28 December 2014. The study protocol (IDC/CL/11/2014, 15 December 2015) had been granted by the Jining Medical College Affiliated Hospital review board. The study adhered standard for CONSORT (Consolidated Standards of Reporting Trials), 2013 Declarations of Helsinki, and the law of China. All enrolled patients had been signed informed concert form before commencement of the study. The approval for publication including all formats (books, electronic journals, research reports) irrespective of time and language had been taken from all participant subjects at the time of enrollment.

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Z., Song, M., He, Z. et al. Comparison of quick recovery outcome of inhalable doxorubicin and cisplatin in lung cancer patients: a randomized, double-blind, single-center trial. Drug Deliv. and Transl. Res. 8, 985–993 (2018). https://doi.org/10.1007/s13346-018-0529-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13346-018-0529-1

Keywords

Search

Navigation