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Cisplatin-based chronotherapy for advanced non-small cell lung cancer patients: a randomized controlled study and its pharmacokinetics analysis

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Abstract

Purpose

We intended to evaluate the superiority of cisplatin-based chronotherapy in the treatment of patients with advanced non-small cell lung cancer (NSCLC) and investigate the relationship between the circadian rhythm and the variability of pharmacokinetics for cisplatin.

Methods

Forty-one patients with advanced NSCLC were divided into two groups with minimization randomization, including routine group (24 cases) and chronotherapy group (17 cases). The clinical effect and toxicity between the two groups were investigated. The population pharmacokinetics of cisplatin was calculated using nonlinear mixed-effects modeling method.

Results

There is no significant difference in total response rate between chronotherapy group (52.94 %) and routine chemotherapy group (50.00 %), p = 0.853. The rate of leucopenia (grade 3 or 4) in chronotherapy group (11.76 %) is significantly lower than that in routine chemotherapy (37.50 %), p < 0.05. The rate of neutropenia (grade 3 or 4) in chronotherapy group (11.76 %) is significantly lower than that in routine chemotherapy group (33.33 %), p < 0.05. The proportion of gastrointestinal toxicity (nausea, grade 1 vs 2) in chronotherapy group is significantly lower than that in routine chemotherapy, p < 0.05. When cisplatin was administered at 18:00, the CL was 1.38- and 1.22-fold higher than those administered at 6:00 for total and unbound cisplatin, respectively (p < 0.05).

Conclusions

Cisplatin-based chronotherapy has advantage in relieving side effects of chemotherapy, and circadian could influence the metabolism of cisplatin, and more clinical researches are needed.

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References

  1. Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA (2008) Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc 83:584–594

    Article  PubMed Central  PubMed  Google Scholar 

  2. Brodowicz T, Krzakowski M, Zwitter M, Tzekova V, Ramlau R, Ghilezan N (2006) Cisplatin and gemcitabine first-line chemotherapy followed by maintenance gemcitabine or best supportive care in advanced non-small cell lung cancer: a phase III trial. Lung Cancer 52:155–163

    Article  PubMed  Google Scholar 

  3. Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S, Szczesna A, Juhasz E (2010) Erlotinib as maintenance treatment in advanced non-small cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol 11:521–529

    Article  CAS  PubMed  Google Scholar 

  4. Nation Comprehensive Cancer Network (2013) Non–small cell lung cancer (version 2.2014). Available: http://www.nccn.org/professionals/physician_gls/pdf/nscl.Pdf. Accessed 21 Jan 2014

  5. Azzoli CG, Temin S, Giaccone G (2012) 2011 focused update of 2009 American Society of Clinical Oncology clinical practice guideline update on chemotherapy for stage IV non-small-cell lung cancer. J Oncol Pract/Am Soc Clin Oncol 8:63–66

    Article  Google Scholar 

  6. Azzoli CG, Giaccone G, Temin S (2010) American Society of Clinical Oncology clinical practice guideline update on chemotherapy for stage IV non-small-cell lung cancer. J Oncol Pract/Am Soc Clin Oncol 6:39–43

    Article  Google Scholar 

  7. Levi F (2006) Chronotherapeutics: the relevance of timing in cancer therapy. Cancer Causes Control 17:611–621

    Article  PubMed  Google Scholar 

  8. Levi F, Zidani R, Vannetzel JM, Perpoint B, Focan C, Faggiuolo R, Chollet P, Garufi C, Itzhaki M, Dogliotti L, Isacobelli S, Adam R, Kunstlinger F, Gastiaburu J, Bismuth H, Jasmin C, Misset JL (1994) Chronomodulated versus fixed-infusion rate delivery of ambulatory chemotherapy with oxaliplatin, fluorouracil, and folinic acid (leucovorin) in patients with colorectal cancer metastases: a randomized multi-institutional trial. J Natl Cancer Inst 86:1608–1617

    Article  CAS  PubMed  Google Scholar 

  9. Focan C, Denis B, Kreutz F, Focan-Henrard D, Levi F (1995) Ambulatory chronochemotherapy with 5-fluorouracil, folinic acid, and carboplatin for advanced non-small cell lung cancer. A phase II feasibility trial. J Infus Chemother 5:148–152

    CAS  PubMed  Google Scholar 

  10. Satoh T, Omuro Y, Sasaki Y, Hamamoto Y, Boku N, Tamura T, Ohtsu A (2012) Pharmacokinetic analysis of capecitabine and cisplatin in combination with trastuzumab in Japanese patients with advanced HER2-positive gastric cancer. Cancer Chemother Pharmacol 69:949–955

    Article  CAS  PubMed  Google Scholar 

  11. Sebestyen J, Garg U, Lewing KB, Warady BA, Abdel-Rahman S, Blowey DL (2010) Cisplatin pharmacokinetics in a child receiving peritoneal dialysis. Pediatr Nephrol 25:1185–1189

    Article  PubMed  Google Scholar 

  12. Verschraegen CF, Skubitz K, Daud A, Kudelka AP, Rabinowitz I, Allievi C, Eisenfeld A, Singer JW, Oldham FB (2009) A phase I and pharmacokinetic study of paclitaxel poliglumex and cisplatin in patients with advanced solid tumors. Cancer Chemother Pharmacol 63:903–910

    Article  CAS  PubMed  Google Scholar 

  13. Specenier PM, Ciuleanu T, Latz JE, Musib LC, Darstein CL, Vermorken JB (2008) Pharmacokinetic evaluation of platinum derived from cisplatin administered alone and with pemetrexed in head and neck cancer patients. Cancer Chemother Pharmacol 64:233–241

    Article  PubMed  Google Scholar 

  14. Urien S, Brain E, Bugat R, Pivot X, Lochon I, Van ML, Vauzelle F, Lokiec F (2005) Pharmacokinetics of platinum after oral or intravenous cisplatin: a phase 1 study in 32 adult patients. Cancer Chemother Pharmacol 55:55–60

    Article  CAS  PubMed  Google Scholar 

  15. Ramon-Lopez A, Escudero-Ortiz V, Carbonell V, Perez-Ruixo JJ, Valenzuela B (2012) Population pharmacokinetics applied to optimising cisplatin doses in cancer patients. Farm Hosp 36:392–402

    Article  CAS  PubMed  Google Scholar 

  16. Urien S, Lokiec F (2004) Population pharmacokinetics of total and unbound plasma cisplatin in adult patients. Br J Clin Pharmacol 57:756–763

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. de Jongh FE, Gallo JM, Shen M, Verweij J, Sparreboom A (2004) Population pharmacokinetics of cisplatin in adult cancer patients. Cancer Chemother Pharmacol 54:105–112

    Article  PubMed  Google Scholar 

  18. Ishibashi T, Yano Y, Oguma T (2003) Population pharmacokinetics of platinum after nedaplatin administration and model validation in adult patients. Br J Clin Pharmacol 56:205–213

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Hanada K, Nishijima K, Ogata H, Atagi S, Kawahara M (2001) Population pharmacokinetic analysis of cisplatin and its metabolites in cancer patients: possible misinterpretation of covariates for pharmacokinetic parameters calculated from the concentrations of unchanged cisplatin, ultrafiltered platinum and total platinum. Jpn J Clin Oncol 31:179–184

    Article  CAS  PubMed  Google Scholar 

  20. Kurihara N, Kubota T, Hoshiya Y, Otani Y, Ando N, Kumai K, Kitajima M (1996) Pharmacokinetics of cis-diamminedichloroplatinum (II) given as low-dose and high-dose infusions. J Surg Oncol 62:135–138

    Article  CAS  PubMed  Google Scholar 

  21. Zhang M (1992) Clinical pharmacokinetics of cis-diamminedichloroplatinum (DDP). Zhonghua Zhong Liu Za Zhi 14:67–69

    CAS  PubMed  Google Scholar 

  22. Hrushesky WJ (1985) Circadian timing of cancer chemotherapy. Science 228:73–75

    Article  CAS  PubMed  Google Scholar 

  23. Levi F, Benavides M, Chevelle C, Le Saunier F, Bailleul F, Misset JL, Regensberg C, Vannetzel JM, Reinberg A, Mathe G (1990) Chemotherapy of advanced ovarian cancer with 4′-O-tetrahydropyranyl doxorubicin and cisplatin: a randomized phase II trial with an evaluation of circadian timing and dose-intensity. J Clin Oncol 8:705–714

    CAS  PubMed  Google Scholar 

  24. Urien S, Lokiec F (2004) Population pharmacokinetics of total and unbound plasma cisplatin in adult patients. Br J Clin Pharmacol 57:756–763

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Chen Rong, Li Jie, Wen-wei Hu, Wang Ming-li, Zou Su-lan, Miao Li-yan (2013) Circadian variability of pharmacokinetics of cisplatin in patients with non-small-cell lung carcinoma: analysis with the NONMEM program. Cancer Chemother Pharmacol 72:1111–1123

    Article  CAS  PubMed  Google Scholar 

  26. Pasquale F, Lévi Francis, Bjarnason Georg A (2010) Chronotherapy and the molecular clock: clinical implications in oncology. Adv Drug Deliv Rev 62:979–1001

    Article  Google Scholar 

  27. Loning Fu, Pelicano H, Liu Jinsong, Huang Peng, Lee Cheng Chi (2002) The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo. Cell 111:41–50

    Article  Google Scholar 

  28. Gachon F, Olela F, Schaad O, Descombes P, Schibler U (2006) The circadian PAR-domain basic leucine zipper transcription factors DBP, TEF and HLF modulate basal and inducible xenobiotic detoxification. Cell Metab 4:25–36

    Article  CAS  PubMed  Google Scholar 

  29. Gery S, Komatsu N, Baldjyan L, Yu A, Koo D, Koeffler H (2006) The circadian gene per1 plays an important role in cell growth and DNA damage control in human cancer cells. Mol Cell 22:375–382

    Article  CAS  PubMed  Google Scholar 

  30. Goldbeter A, Claude D (2002) Time-patterned drug administration: insights from a modeling approach. Chronobiol Int 19:157–175

    Article  CAS  Google Scholar 

  31. Altinoka A, Levi F, Goldbetera A (2009) Identifying mechanisms of chronotolerance and chronoefficacy for the anticancer drugs 5-fluorouracil and oxaliplatin by computational modeling. Eur J Pharm Sci 36:20–38

    Article  Google Scholar 

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Acknowledgments

We gratefully appreciate and thank the patients for participating in this study, as well as the nursing staff of the Oncology ward for their assistance.

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Clinical pharmacy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiang Su, China

    Jie Li, Rong Chen & Su-lan Zou

  2. Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiang Su, China

    Mei Ji & Li-na Zhu

Authors
  1. Jie Li
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  2. Rong Chen
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  3. Mei Ji
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  4. Su-lan Zou
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Correspondence to Jie Li.

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Li, J., Chen, R., Ji, M. et al. Cisplatin-based chronotherapy for advanced non-small cell lung cancer patients: a randomized controlled study and its pharmacokinetics analysis. Cancer Chemother Pharmacol 76, 651–655 (2015). https://doi.org/10.1007/s00280-015-2804-x

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  • DOI: https://doi.org/10.1007/s00280-015-2804-x

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