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Published in: Cancer Chemotherapy and Pharmacology 2/2011

01-08-2011 | Original Article

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

Authors: Kohei Shitara, Keitaro Matsuo, Isao Oze, Ayako Mizota, Chihiro Kondo, Motoo Nomura, Tomoya Yokota, Daisuke Takahari, Takashi Ura, Kei Muro

Published in: Cancer Chemotherapy and Pharmacology | Issue 2/2011

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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.
Literature
2.
go back to reference 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 45:1757–1763PubMedCrossRef 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 45:1757–1763PubMedCrossRef
3.
go back to reference 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 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.
go back to reference 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 17:1–12PubMedCrossRef 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 17:1–12PubMedCrossRef
5.
go back to reference 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 75:301–305PubMedCrossRef 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 75:301–305PubMedCrossRef
6.
go back to reference 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 80:1763–1766PubMedCrossRef 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 80:1763–1766PubMedCrossRef
7.
go back to reference 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 6:669–677PubMedCrossRef 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 6:669–677PubMedCrossRef
8.
go back to reference 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 23:8003–8011PubMedCrossRef 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 23:8003–8011PubMedCrossRef
9.
go back to reference 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 97:37–42PubMedCrossRef 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 97:37–42PubMedCrossRef
10.
go back to reference 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 62:356–363PubMedCrossRef 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 62:356–363PubMedCrossRef
11.
go back to reference 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 89:623–628PubMedCrossRef 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 89:623–628PubMedCrossRef
12.
go back to reference 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 101:1537–1542PubMedCrossRef 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 101:1537–1542PubMedCrossRef
13.
go back to reference 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 99:302–306PubMedCrossRef 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 99:302–306PubMedCrossRef
14.
go back to reference 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 20:146–150PubMedCrossRef 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 20:146–150PubMedCrossRef
15.
go back to reference 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 78:213–219PubMedCrossRef 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 78:213–219PubMedCrossRef
16.
go back to reference 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 66:8–14PubMedCrossRef 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 66:8–14PubMedCrossRef
17.
go back to reference 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 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
18.
go back to reference 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 26:2099–2105PubMedCrossRef 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 26:2099–2105PubMedCrossRef
19.
go back to reference Ratain MJ (1998) Body-surface area as a basis for dosing anticancer agents: science, myth, or habit? J Clin Oncol 16:2297–2298PubMed Ratain MJ (1998) Body-surface area as a basis for dosing anticancer agents: science, myth, or habit? J Clin Oncol 16:2297–2298PubMed
20.
go back to reference 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 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.
go back to reference 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 15:781–792CrossRef 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 15:781–792CrossRef
22.
go back to reference 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 13:308–317PubMedCrossRef 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 13:308–317PubMedCrossRef
Metadata
Title
Meta-analysis of neutropenia or leukopenia as a prognostic factor in patients with malignant disease undergoing chemotherapy
Authors
Kohei Shitara
Keitaro Matsuo
Isao Oze
Ayako Mizota
Chihiro Kondo
Motoo Nomura
Tomoya Yokota
Daisuke Takahari
Takashi Ura
Kei Muro
Publication date
01-08-2011
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 2/2011
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-010-1487-6

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