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Meta-analysis of neutropenia or leukopenia as a prognostic factor in patients with malignant disease undergoing chemotherapy

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Abstract

Purpose

We performed a systematic review and meta-analysis to determine the impact of neutropenia or leukopenia experienced during chemotherapy on survival.

Methods

Eligible studies included prospective or retrospective analyses that evaluated neutropenia or leukopenia as a prognostic factor for overall survival or disease-free survival. Statistical analyses were conducted to calculate a summary hazard ratio and 95% confidence interval (CI) using random-effects or fixed-effects models based on the heterogeneity of the included studies.

Results

Thirteen trials were selected for the meta-analysis, with a total of 9,528 patients. The hazard ratio of death was 0.69 (95% CI, 0.64–0.75) for patients with higher-grade neutropenia or leukopenia compared to patients with lower-grade or lack of cytopenia. Our analysis was also stratified by statistical method (any statistical method to decrease lead-time bias; time-varying analysis or landmark analysis), but no differences were observed.

Conclusions

Our results indicate that neutropenia or leukopenia experienced during chemotherapy is associated with improved survival in patients with advanced cancer or hematological malignancies undergoing chemotherapy. Future prospective analyses designed to investigate the potential impact of chemotherapy dose adjustment coupled with monitoring of neutropenia or leukopenia on survival are warranted.

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References

  1. Gurney H (2002) How to calculate the dose of chemotherapy. Br J Cancer 86:1297–1302

    Article  PubMed  CAS  Google Scholar 

  2. Shitara K, Matsuo K, Takahari D, Yokota T, Inaba Y, Yamaura H, Sato Y, Najima M, Ura T, Muro K (2009) Neutropenia as a prognostic factor in metastatic colorectal cancer patients undergoing chemotherapy with first-line FOLFOX. Eur J Cancer 45:1757–1763

    Article  PubMed  CAS  Google Scholar 

  3. Shitara K, Matsuo K, Takahari D, Yokota T, Shibata T, Ura T, Ito S, Sawaki A, Tajika M, Kawai H, Muro K (2010) Neutropenia as a prognostic factor in advanced gastric cancer patients undergoing second-line chemotherapy with weekly paclitaxel. Annals of Oncology; in press

  4. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12

    Article  PubMed  CAS  Google Scholar 

  5. Saarto T, Blomqvist C, Rissanen P, Auvinen A, Elomaa I (1997) Haematological toxicity: a marker of adjuvant chemotherapy efficacy in stage II and III breast cancer. Br J Cancer 75:301–305

    Article  PubMed  CAS  Google Scholar 

  6. Poikonen P, Saarto T, Lundin J, Joensuu H, Blomqvist C (1999) Leucocyte nadir as a marker for chemotherapy efficacy in node-positive breast cancer treated with adjuvant CMF. Br J Cancer 80:1763–1766

    Article  PubMed  CAS  Google Scholar 

  7. Di Maio M, Gridelli C, Gallo C, Shepherd F, Piantedosi FV, Cigolari S, Manzione L, Illiano A, Barbera S, Robbiati SF, Frontini L, Piazza E, Ianniello GP, Veltri E, Castiglione F, Rosetti F, Gebbia V, Seymour L, Chiodini P, Perrone F (2005) Chemotherapy-induced neutropenia and treatment efficacy in advanced non-small-cell lung cancer: a pooled analysis of three randomised trials. Lancet Oncol 6:669–677

    Article  PubMed  CAS  Google Scholar 

  8. Klimm B, Reineke T, Haverkamp H, Behringer K, Eich HT, Josting A, Pfistner B, Diehl V, Engert A (2005) Role of hematotoxicity and sex in patients with Hodgkin’s lymphoma: an analysis from the German Hodgkin Study Group. J Clin Oncol 23:8003–8011

    Article  PubMed  CAS  Google Scholar 

  9. Yamanaka T, Matsumoto S, Teramukai S, Ishiwata R, Nagai Y, Fukushima M (2007) Predictive value of chemotherapy-induced neutropaeniafor the efficacy of oral fluoropyrimidine S-1 in advanced gastric carcinoma. Br J Cancer 97:37–42

    Article  PubMed  CAS  Google Scholar 

  10. Pallis AG, Agelaki S, Kakolyris S, Kotsakis A, Kalykaki A, Vardakis N, Papakotoulas P, Agelidou A, Geroyianni A, Agelidou M, Hatzidaki D, Mavroudis D, Georgoulias V (2008) Chemotherapy-induced neutropenia as a prognostic factor in patients with advanced non-small cell lung cancer treated with front-line docetaxel-gemcitabine chemotherapy. Lung Cancer 62:356–363

    Article  PubMed  CAS  Google Scholar 

  11. Kim JJ, Park JY, Kim DY, Kim JH, Kim YM, Nam JH, Kim YT (2010) Is chemotherapy-induced neutropenia a prognostic factor in patients with ovarian cancer? Acta Obstet Gynecol Scand 89:623–628

    Article  PubMed  CAS  Google Scholar 

  12. Kishida Y, Kawahara M, Teramukai S, Kubota K, Komuta K, Minato K, Mio T, Fujita Y, Yonei T, Nakano K, Tsuboi M, Shibata K, Atagi S, Kawaguchi T, Furuse K, Fukushima M (2009) Chemotherapy-induced neutropenia as a prognostic factor in advanced non-small-cell lung cancer: results from Japan Multinational Trial Organization LC00–03. Br J Cancer 101:1537–1542

    Article  PubMed  CAS  Google Scholar 

  13. Miyoshi N, Yano M, Takachi K, Kishi K, Noura S, Eguchi H, Yamada T, Miyashiro I, Ohue M, Ohigashi H, Sasaki Y, Ishikawa O, Doki Y, Imaoka S (2009) Myelotoxicity of preoperative chemoradiotherapy is a significant determinant of poor prognosis in patients with T4 esophageal cancer. J Surg Oncol 99:302–306

    Article  PubMed  CAS  Google Scholar 

  14. Kim YH, Chung HH, Kim JW, Park NH, Song YS, Kang SB (2009) Prognostic significance of neutropenia during adjuvant concurrent chemoradiotherapy in early cervical cancer. J Gynecol Oncol 20:146–150

    Article  PubMed  Google Scholar 

  15. Ishitobi M, Komoike Y, Motomura K, Koyama H, Inaji H (2010) Prognostic significance of neutropenia on day one of anthracycline-based neoadjuvant chemotherapy in operable breast cancer. Oncology 78:213–219

    Article  PubMed  CAS  Google Scholar 

  16. Maione P, Rossi A, Di Maio M, Gridelli C (2009) Tumor-related leucocytosis and chemotherapy-induced neutropenia: linked or independent prognostic factors for advanced non-small cell lung cancer? Lung Cancer 66:8–14

    Article  PubMed  Google Scholar 

  17. Gurney HP, Ackland S, Gebski V, Farrell G (1998) Factors affecting epirubicin pharmacokinetics and toxicity: evidence against using body-surface area for dose calculation. J Clin Oncol 6:2299–2304

    Google Scholar 

  18. Gamelin E, Delva R, Jacob J, Merrouche Y, Raoul JL, Pezet D, Dorval E, Piot G, Morel A, Boisdron-Celle M (2008) Individual fluorouracil dose adjustment based on pharmacokinetic follow-up compared with conventional dosage: results of a multicenter randomized trial of patients with metastatic colorectal cancer. J Clin Oncol 26:2099–2105

    Article  PubMed  CAS  Google Scholar 

  19. Ratain MJ (1998) Body-surface area as a basis for dosing anticancer agents: science, myth, or habit? J Clin Oncol 16:2297–2298

    PubMed  CAS  Google Scholar 

  20. Vermorken JB, Viret F, Glimelius B, Ciardiello F, Gallerani E, Amellal N, Peeters M (2007) Cetuximab dose-escalation study in patients with metastatic colorectal cancer (mCRC) with no or slight skin reactions on cetuximab standard dose treatment (EVEREST): pharmacokinetic and efficacy data of a randomized study. Gastrointestinal cancers symposium. Abstract 237

  21. Mandrekar SJ, Schild SE, Hillman SL, Allen KL, Marks RS, Mailliard JA, Krook JE, Maksymiuk AW, Chansky K, Kelly K, Adjei AA, Jett JR (2006) A prognostic model for advanced stage nonsmall cell lung cancer. Pooled analysis of North Central Cancer Treatment Group trials. Cancer 15:781–792

    Article  Google Scholar 

  22. Köhne CH, Cunningham D, Di CF, Glimelius B, Blijham G, Aranda E, Scheithauer W, Rougier P, Palmer M, Wils J, Baron B, Pignatti F, Schöffski P, Micheel S, Hecker H (2002) Clinical determinants of survival in patients with 5-fluorouracil-based treatment for metastatic colorectal cancer: results of a multivariate analysis of 3825 patients. Ann Oncol 13:308–317

    Article  PubMed  Google Scholar 

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Conflict of interest

None of the authors have financial or personal conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Clinical Oncology, Aichi Cancer Center Hospital, Chikusa-ku, Nagoya, Japan

    Kohei Shitara, Ayako Mizota, Chihiro Kondo, Motoo Nomura, Tomoya Yokota, Daisuke Takahari, Takashi Ura & Kei Muro

  2. Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Keitaro Matsuo & Isao Oze

Authors
  1. Kohei Shitara
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  2. Keitaro Matsuo
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  3. Isao Oze
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  4. Ayako Mizota
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  5. Chihiro Kondo
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  6. Motoo Nomura
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  7. Tomoya Yokota
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  8. Daisuke Takahari
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  9. Takashi Ura
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  10. Kei Muro
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Correspondence to Keitaro Matsuo.

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Shitara, K., Matsuo, K., Oze, I. et al. Meta-analysis of neutropenia or leukopenia as a prognostic factor in patients with malignant disease undergoing chemotherapy. Cancer Chemother Pharmacol 68, 301–307 (2011). https://doi.org/10.1007/s00280-010-1487-6

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  • DOI: https://doi.org/10.1007/s00280-010-1487-6

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