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Pseudomonas aeruginosa preparation plus chemotherapy for advanced non-small-cell lung cancer: a randomized, multicenter, double-blind phase III study

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Abstract

Pseudomonas aeruginosa preparation (PAP) has shown activity in inhibiting the metastasis of cancer and can improve the immune function of cancer patients during chemotherapy. This study aimed to investigate whether PAP can improves the efficacy of chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). A total of 72 subjects with stage IIIB/IV NSCLC were randomized into PAP arm (n = 36) or control arm (n = 36) at a 1:1 ratio. Subjects had vinorelbine and cisplatin combined with 0.5 ml PAP/placebo on d1, followed by 1 ml PAP/placebo injected subcutaneously three times a week. The primary end point was the objective response rate (ORR) and secondary endpoints were time to progression (TTP), overall survival (OS), safety and quality of life (QOL). Sixty-six patients were included in intent-to-treat analysis. After two cycles of treatment, there was a borderline statistically significant improvement in ORR of PAP arm (46.88 vs. 23.53 %, P = 0.0532), and after four cycles of treatment, the ORR in PAP arm was 31.25 versus 14.71 % in control arm (P = 0.1110). Median TTP and OS were 160 and 454 days in PAP arm, 196 and 388 days in control arm, P = 0.4609 and 0.6587, respectively. The 1-year survival rate in PAP and control arms was 53.55 and 50.15 %, respectively. PAP did not result in increased toxicity and or had negative impact on QOL. The results demonstrate the therapeutic potential of PAP for advanced NSCLC. PAP can be used with chemotherapy to improve the response rate. Long-term follow-up might help define whether the combination therapy can result in survival benefit.

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References

  1. Gridelli C, Rossi A, Maione P, Ferrara ML, Castaldo V, Sacco PC. Vaccines for the treatment of non-small cell lung cancer: a renewed anticancer strategy. Oncologist. 2009;14(9):909–20.

    Article  CAS  PubMed  Google Scholar 

  2. Pirker R, Pereira JR, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Vynnychenko I, Park K, Yu CT, Ganul V, Roh JK, Bajetta E, O’Byrne K, de Marinis F, Eberhardt W, Goddemeier T, Emig M, Gatzemeier U, FLEX Study Team. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009;373(9674):1525–31.

    Article  CAS  PubMed  Google Scholar 

  3. Butts C, Murray N, Maksymiuk A, Goss G, Marshall E, Soulières D, Cormier Y, Ellis P, Price A, Sawhney R, Davis M, Mansi J, Smith C, Vergidis D, Ellis P, MacNeil M, Palmer M. Randomized phase IIB trial of BLP25 liposome vaccine in stage IIIB and IV non-small-cell lung cancer. J Clin Oncol. 2005;23(27):6674–81.

    Article  CAS  PubMed  Google Scholar 

  4. Vansteenkiste J, Zielinski M, Linder A, Dahabre J, Esteban E, Malinowski W, Jassem J, Passlick B, Lehmann F, Brichard VG. Final results of a multi-center, double-blind, randomized, placebo-controlled phase II study to assess the efficacy of MAGE-A3 immunotherapeutic as adjuvant therapy in stage IB/II non-small cell lung cancer (NSCLC). J Clin Oncol. 2007;25(18S):7554.

    Google Scholar 

  5. Kodama K, Higashiyama M, Takami K, Oda K, Okami J, Maeda J, Akazawa T, Matsumoto M, Seya T, Wada M, Toyoshima K. Innate immune therapy with a bacillus Calmette–Guerin cell wall skeleton after radical surgery for non-small cell lung cancer: a case–control study. Surg Today. 2009;39(3):194–200.

    Article  PubMed  Google Scholar 

  6. Manegold C, Gravenor D, Woytowitz D, Mezger J, Hirsh V, Albert G, Al-Adhami M, Readett D, Krieg AM, Leichman CG. Randomized phase II trial of a toll-like receptor 9 agonist oligodeoxynucleotide, PF-3512676, in combination with first-line taxane plus platinum chemotherapy for advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008;26(24):3979–86.

    Article  CAS  PubMed  Google Scholar 

  7. Mossman KL, Mian MF, Lauzon NM, Gyles CL, Lichty B, Mackenzie R, Gill N, Ashkar AA. Cutting edge: FimH adhesin of type 1 fimbriae is a novel TLR4 ligand. J Immunol. 2008;181(10):6702–6.

    Article  CAS  PubMed  Google Scholar 

  8. Liu ZB, Hou YF, Dong M, Di GH, Wu J, Shen ZZ, Shao ZM. PA-MSHA inhibits proliferation and induces apoptosis through the up-regulation and activation of caspases in the human breast cancer cell lines. J Cell Biochem. 2009;108(1):195–206.

    Article  CAS  PubMed  Google Scholar 

  9. Cao Z, Shi L, Li Y, Wang J, Wang D, Wang G, Sun B, Mu L, Yang M, Li H. Pseudomonas aeruginosa: mannose sensitive hemagglutinin inhibits the growth of human hepatocarcinoma cells via mannose-mediated apoptosis. Dig Dis Sci. 2009;54(10):2118–27.

    Article  PubMed  Google Scholar 

  10. Liu ZB, Hou YF, Zhu J, Hu DL, Jin W, Ou ZL, Di GH, Wu J, Shen ZZ, Shao ZM. Inhibition of EGFR pathway signaling and the metastatic potential of breast cancer cells by PA-MSHA mediated by type 1 fimbriae via a mannose-dependent manner. Oncogene. 2010;29(20):2996–3009.

    Article  CAS  PubMed  Google Scholar 

  11. Chen WD, Tang ZH, Xu F. Application of PA-MSHA vaccine adjuvant therapy and TAC scheme for treatment of breast carcinoma. Nan Fang Yi Ke Da Xue Xue Bao. 2009;29(6):1204–7.

    PubMed  Google Scholar 

  12. Li Z, Hao D, Zhang H, Ren L, Yang Y, Li L, Chai J, Zhou X, Fu L. A clinical study on PA-MSHA vaccine used for adjuvant therapy of lymphoma and lung cancer. Hua Xi Yi Ke Da Xue Xue Bao. 2000;31(3):334–7.

    CAS  PubMed  Google Scholar 

  13. Chan CW, Housseau F. The ‘kiss of death’ by dendritic cells to cancer cells. Cell Death Differ. 2008;15(1):58–69.

    Article  CAS  PubMed  Google Scholar 

  14. Willimsky G, Blankenstein T. Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance. Nature. 2005;437(7055):141–6.

    Article  CAS  PubMed  Google Scholar 

  15. Atreya I, Neurath MF. Immune cells in colorectal cancer: prognostic relevance and therapeutic strategies. Expert Rev Anticancer Ther. 2008;8(4):561–72.

    Article  CAS  PubMed  Google Scholar 

  16. Akira S. Pathogen recognition by innate immunity and its signaling. Proc Jpn Acad Ser B Phys Biol Sci. 2009;85(4):143–56.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Hobohm U, Stanford JL, Grange JM. Pathogen-associated molecular pattern in cancer immunotherapy. Crit Rev Immunol. 2008;28(2):95–107.

    Article  CAS  PubMed  Google Scholar 

  18. Coley WB. The treatment of malignant tumors by repeated inoculations of erysipelas. With a report of ten original cases. Clin Orthop Relat Res. 1991;262:3–11.

    PubMed  Google Scholar 

  19. Talug C, Brown ET, Zaslau S, Kandzari SJ. Use of bacillus Calmette–Guerin in superficial bladder cancer: a review. W V Med J. 2009;105(3):17–9.

    PubMed  Google Scholar 

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Conflict of interest

The authors declare no conflict of interest.

Ethical standard

The study has been approved by the appropriate ethics committee and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All persons gave their informed consent prior to their inclusion in the study. Details that might disclose the identity of the subjects under study have been omitted.

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Authors and Affiliations

  1. Department of Medical Oncology, Fudan University Shanghai Cancer Center, No. 270 Dong’an Road, Shanghai, 200032, China

    Jianhua Chang & Jin Li

  2. Department of Medical Oncology, The First Affiliated Hospital of China Medical University, No. 155 North Nanjing Road, Shenyang, 110001, China

    Yunpeng Liu

  3. Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiaotong University, No. 241 West Huaihai Road, Shanghai, 200030, China

    Baohui Han

  4. Department of Oncology, Shanghai Pulmonary Hospital, Tongji University, No. 507 Zhengmin Road, Shanghai, 200433, China

    Caicun Zhou

  5. Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China

    Chunxue Bai

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  1. Jianhua Chang
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  2. Yunpeng Liu
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  3. Baohui Han
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  4. Caicun Zhou
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  5. Chunxue Bai
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  6. Jin Li
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Correspondence to Jin Li.

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Chang, J., Liu, Y., Han, B. et al. Pseudomonas aeruginosa preparation plus chemotherapy for advanced non-small-cell lung cancer: a randomized, multicenter, double-blind phase III study. Med Oncol 32, 139 (2015). https://doi.org/10.1007/s12032-015-0583-1

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  • DOI: https://doi.org/10.1007/s12032-015-0583-1

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