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Association of Chemotherapy-induced Leucopenia with Treatment Outcomes in Advanced Non-small-cell lung Cancer Cases Receiving the NP Regimen

  • Published : 2012.09.30

Abstract

Background: Chemotherapy induced leutropenia has been shown to be associated with improved treatment outcomes in selected solid tumors. We studied the association of chemotherapy induced leutropenia with treatment related outcomes in advanced non-small-cell lung cancer. Methods: This is a prospective analysis of patients receiving chemotherapy for advanced NSCLC at the Shandong Cancer Hospital from 2005-07.The chemotherapy included cisplatin $35mg/m^2$, IV on $d_{1,2}$ and vinorelbine $25mg/m^2$ IV on $d_{1,8}$ every 21 days. Patients were stratified into three groups (A) those experiencing grades 0 leucopenia, group (B) grades 1-2 and group (C) grades 3-4. The outcomes studied were response rate (RR), disease control rate (DCR), and time to progression (TTP). Results: 128 patients were studied. The RRs in groups A, B and C were 30.8%, 56.8% and 71.4%, respectively, p=0.010. The DCRs were 61.5%, 83.8% and 92.9%, respectively, p=0.009 and the median TTPs were 150 days (95%CI: 91-209), 189 days (95%CI: 181-197) and 207 days (95%CI: 172-242), p=0.009. The differences in RR and TTP were significant. In patients whose CIL kept on 10 days at least, the TTP was significantly prolonged, p=0.0213, and the same was the case for those experiencing grades 1-2 leucopenia and ECOG 0, p=0.0412. Conclusions: Occurrence of CIL correlated with RR and TTP in patients with advanced NSCLC receiving cisplatin and vinorelbine chemotherapy, especially in patients experiencing grades 1-2 leucopenia and ECOG 0, and the same for those with CIL persisting for 10 days at least. CIL could be a biological measure of drug activity and a marker of efficacy.

Keywords

References

  1. Banerji U, Ashley S, Coward J, et al (2006). The association of chemotherapy induced neutropenia on treatment outcomes in small cell lung cancer. Lung Cancer, 54, 371-7. https://doi.org/10.1016/j.lungcan.2006.08.001
  2. Brunetto AT, Carden CP, Myerson J, et al (2010). Modest reductions in dose intensity and drug-induced neutropenia have no major impact on survival of patients with non-small cell lung cancer treated with platinum-doublet chemotherapy. J Thorac Oncol, 5, 1397-403. https://doi.org/10.1097/JTO.0b013e3181eba7f9
  3. Cameron DA, Massie C, Kerr G, et al (2003). Moderate neutropenia with adjuvant CMF confers improved survival in early breast cancer. Br J Cancer, 89, 1837-42. https://doi.org/10.1038/sj.bjc.6601366
  4. Camps CR, De Las Peñas G, López-Vivanco, et al (2006). Chemotherapy -induced neutropenia and treatment efficacy in advanced non-small cell lung cancer: An analysis of the Spanish Lung Cancer Group pharmacogenomic study of cisplatin and docetaxel combination (PLATAX). J Clin Oncol; ASCO Annual Meeting Proceedings Part I, 4, 18S, 7124.
  5. Delbaldo C, Michiels S, Syz N, et al (2004). Benefits of adding a drug to a single-agent or a 2-agent chemotherapy regimen in advanced non-small-cell lung cancer: a meta-analysis. JAMA, 292, 470-84. https://doi.org/10.1001/jama.292.4.470
  6. Di Maio M, Gridelli C, Gallo C, et al (2005). Chemotherapyinduced neutropenia and treatment efficacy in advanced nonsmall- cell lung cancer: a pooled analysis of three randomised trials. Lancet Oncol, 6, 669-77. https://doi.org/10.1016/S1470-2045(05)70255-2
  7. Gridelli C, Gallo C, Shepherd FA, et al (2003). Gemcitabine plus vinorelbine compared to cisplatin plus vinorelbine or cisplatin plus gemcitabine for advanced non-small-cell lung cancer. A phase III trial of the Italian GEMVIN Investigators and the National Cancer Institute of Canada-Clinical Trials Group. J Clin Oncol, 21, 3025-34. https://doi.org/10.1200/JCO.2003.06.099
  8. Gridelli C, Perrone F, Gallo C, et al (2003). Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst, 95, 362-72. https://doi.org/10.1093/jnci/95.5.362
  9. Gurney H (2002). How to calculate the dose of chemotherapy. Br J Cancer, 86, 1297-302. https://doi.org/10.1038/sj.bjc.6600139
  10. Han Y, Yu Z, Wen S, et al (2012). Prognostic value of chemotherapy-induced neutropenia in early-stage breast cancer. Breast Cancer Res Treat, 131, 483-90. https://doi.org/10.1007/s10549-011-1799-1
  11. Hangaishi A (2011). The strategy for chemotherapy-induced myelosuppression. Gan To Kagaku Ryoho, 38, 1777-81.
  12. Kishida Y, Kawahara M, Teramukai S, et al (2009). Chemotherapyinduced neutropenia as a prognostic factor in advanced nonsmall-cell lung cancer: results from Japan Multinational Trial Organization LC00-03. Br J Cancer, 101, 1537-42. https://doi.org/10.1038/sj.bjc.6605348
  13. Kvinnsland S (1999). The leucocyte nadir, a predictor of chemotherapy efficacy? Br J Cancer, 80, 1681. https://doi.org/10.1038/sj.bjc.6690583
  14. Lyman GH, Michels SL, Reynolds MW, et al (2010). Risk of mortality in patients with cancer who experience febrile neutropenia Cancer. Cancer, 116, 5555-63. https://doi.org/10.1002/cncr.25332
  15. Lyman GH, Kleiner JM (2011). Summary and comparison of myeloid growth factor guidelines in patients receiving cancer chemotherapy. Cancer Treat Res, 157, 145-65.
  16. Massimo DM, Cesare G, Ciro G, et al (2006). Chemotherapy -induced neutropenia: a useful predictor of treatment efficacy? Nature Clin Prac Oncol, 3, 114-5. https://doi.org/10.1038/ncponc0445
  17. Pfister DG, Johnson DH, Azzoli CG, et al (2004). American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: update 2003. J Clin Oncol, 22, 330-53.
  18. Poikonen P, Saarto T, Lundin J, et al (1999). Leucocyte nadir as a marker for chemotherapy efficacy in node-positive breast cancer treated with adjuvant CMF. Br J Cancer, 80,1763-6. https://doi.org/10.1038/sj.bjc.6690594
  19. Ratain MJ (1998). Body-surface area as a basis for dosing anticancer agents: science, myth, or habit? J Clin Oncol, 16, 2297-8.
  20. Saarto T, Blomqvist C, Rissanen P, et al (1997). Haematological toxicity: a marker of adjuvant chemotherapy efficacy in stage II and III breast cancer. Br J Cancer, 75, 301-5. https://doi.org/10.1038/bjc.1997.49
  21. Saloustros E, Tryfonidis K, Georgoulias V (2011). Prophylactic and therapeutic strategies in chemotherapy-induced neutropenia. Expert Opin Pharmacother, 12, 851-63. https://doi.org/10.1517/14656566.2011.541155
  22. Sawyer M, Ratain MJ (2001). Body surface area as a determinant of harmacokinetics and drug dosing. Investigational New Drugs, 19, 171-7. https://doi.org/10.1023/A:1010639201787
  23. Schiller JH, Harrington D, Belani CP, et al (2002). Eastern Cooperative Oncology Group.Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med, 346, 92-8. https://doi.org/10.1056/NEJMoa011954
  24. Shitara K, Matsuo K, Oze I, et al (2011). Meta-analysis of neutropenia or leukopenia as a prognostic factor in patients with malignant disease undergoing chemotherapy. Cancer Chemother Pharmacol, 68, 301-7. https://doi.org/10.1007/s00280-010-1487-6
  25. Shitara K, Matsuo K, Takahari D, et al (2010). Neutropenia as a prognostic factor in advanced gastric cancer patients undergoing second-line chemotherapy with weekly paclitaxel. Ann Oncol, 21, 2403-9. https://doi.org/10.1093/annonc/mdq248
  26. Singh S, Parulekar W, Murray N, et al (2005). Influence of sex on toxicity and treatment outcome in small cell lung cancer. J Clin Oncol, 23, 850-6. https://doi.org/10.1200/JCO.2005.03.171
  27. Souza-Dantas VC, Salluh JI, Soares M (2011). Impact of neutropenia on the outcomes of critically ill patients with cancer: a matched case-control study. Ann Oncol, 22, 2094-100. https://doi.org/10.1093/annonc/mdq711

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