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Published in: Drugs 7/2018

01-05-2018 | Review Article

Chemotherapy-Induced Neutropenia as a Prognostic and Predictive Marker of Outcomes in Solid-Tumor Patients

Authors: Pashtoon Murtaza Kasi, Axel Grothey

Published in: Drugs | Issue 7/2018

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Abstract

Chemotherapy-induced neutropenia (CIN) is one of the most common side effects seen in cancer patients. As an adverse event, it is deemed undesirable since it often constitutes a dose-limiting toxicity for cytotoxic agents leading to treatment delays and/or dose reductions. It is also associated with a financial cost component from diagnostic work-up and treatment of patients with chemotherapy-induced febrile neutropenia (CIFN). Neutropenia is commonly accompanied by a decrease in other hematopoietic lineages (anemia and/or thrombocytopenia). Dosing of chemotherapeutic agents is based on the severity of adverse effects seen. Depending on the degree of neutropenia, chemotherapeutic agents may be put on hold until count recovery and growth factor support might be added to allow for dosing as scheduled. However, neutropenia appears to be more than just an adverse event. While CIFN by itself constitutes an adverse event, the appearance of just CIN is not necessarily a marker of poor outcome. In fact, it rather appears to be a surrogate marker of response and/or survival in patients treated with cytotoxic regimens. Here we present evidence in different tumor types treated with different regimens on the role CIN plays as a marker for improved outcomes. If CIN is a surrogate prognostic and/or potentially predictive marker of response, chemotherapy doses may need to be escalated to achieve neutropenia. In addition, instead of reducing treatment doses for safety concerns, the addition of growth factor support and alternative dosing schemes may be strategies to consider.
Literature
1.
go back to reference Jacobs VR, Mayer SC, Paessens B, Anker G, Schwarz-Boeger U, Paepke S, et al. Prospective study comparing hospital costs and DRG reimbursement of inpatient treatment of febrile neutropenia during adjuvant anthracycline-based CTX for primary breast cancer. J Clin Oncol. 2009;27(15_suppl):e11570. Jacobs VR, Mayer SC, Paessens B, Anker G, Schwarz-Boeger U, Paepke S, et al. Prospective study comparing hospital costs and DRG reimbursement of inpatient treatment of febrile neutropenia during adjuvant anthracycline-based CTX for primary breast cancer. J Clin Oncol. 2009;27(15_suppl):e11570.
2.
go back to reference Bottsford-Miller J, Choi HJ, Dalton HJ, Stone RL, Cho MS, Haemmerle M, et al. Differential platelet levels affect response to taxane-based therapy in ovarian cancer. Clin Cancer Res. 2015;21(3):602–10.CrossRefPubMed Bottsford-Miller J, Choi HJ, Dalton HJ, Stone RL, Cho MS, Haemmerle M, et al. Differential platelet levels affect response to taxane-based therapy in ovarian cancer. Clin Cancer Res. 2015;21(3):602–10.CrossRefPubMed
3.
go back to reference Mayer RJ, Van Cutsem E, Falcone A, Yoshino T, Garcia-Carbonero R, Mizunuma N, et al. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med. 2015;372(20):1909–19.CrossRefPubMed Mayer RJ, Van Cutsem E, Falcone A, Yoshino T, Garcia-Carbonero R, Mizunuma N, et al. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med. 2015;372(20):1909–19.CrossRefPubMed
4.
go back to reference Kasi PM, Kotani D, Cecchini M, Shitara K, Ohtsu A, Ramanathan RK, et al. Chemotherapy induced neutropenia at 1-month mark is a predictor of overall survival in patients receiving TAS-102 for refractory metastatic colorectal cancer: a cohort study. BMC Cancer. 2016;16:467.CrossRefPubMedPubMedCentral Kasi PM, Kotani D, Cecchini M, Shitara K, Ohtsu A, Ramanathan RK, et al. Chemotherapy induced neutropenia at 1-month mark is a predictor of overall survival in patients receiving TAS-102 for refractory metastatic colorectal cancer: a cohort study. BMC Cancer. 2016;16:467.CrossRefPubMedPubMedCentral
6.
go back to reference Sunaga T, Suzuki S, Kogo M, Kurihara T, Kaji S, Koike N, et al. The association between neutropenia and prognosis in stage III colorectal cancer patients receiving adjuvant chemotherapy. Eur J Cancer Care (Engl). 2014;23(3):394–400.CrossRef Sunaga T, Suzuki S, Kogo M, Kurihara T, Kaji S, Koike N, et al. The association between neutropenia and prognosis in stage III colorectal cancer patients receiving adjuvant chemotherapy. Eur J Cancer Care (Engl). 2014;23(3):394–400.CrossRef
7.
go back to reference Innominato PF, Giacchetti S, Moreau T, Smaaland R, Focan C, Bjarnason GA, et al. Prediction of survival by neutropenia according to delivery schedule of oxaliplatin-5-fluorouracil-leucovorin for metastatic colorectal cancer in a randomized international trial (EORTC 05963). Chronobiol Int. 2011;28(7):586–600.CrossRefPubMed Innominato PF, Giacchetti S, Moreau T, Smaaland R, Focan C, Bjarnason GA, et al. Prediction of survival by neutropenia according to delivery schedule of oxaliplatin-5-fluorouracil-leucovorin for metastatic colorectal cancer in a randomized international trial (EORTC 05963). Chronobiol Int. 2011;28(7):586–600.CrossRefPubMed
8.
go back to reference Innominato PF, Giacchetti S, Smaaland R, Focan CN, Garufi C, Bjarnason GA, et al. Chemotherapy-induced neutropenia association with survival in metastatic colorectal cancer (MCC): schedule dependency. J Clin Oncol. 2011;29(4_suppl):454.CrossRef Innominato PF, Giacchetti S, Smaaland R, Focan CN, Garufi C, Bjarnason GA, et al. Chemotherapy-induced neutropenia association with survival in metastatic colorectal cancer (MCC): schedule dependency. J Clin Oncol. 2011;29(4_suppl):454.CrossRef
9.
go back to reference Shitara K, Matsuo K, Takahari D, Yokota T, Ura T, Muro K. Neutropenia as a prognostic factor in metastatic colorectal cancer patients undergoing chemotherapy with first-line FOLFOX. J Clin Oncol. 2009;27(15_suppl):4115. Shitara K, Matsuo K, Takahari D, Yokota T, Ura T, Muro K. Neutropenia as a prognostic factor in metastatic colorectal cancer patients undergoing chemotherapy with first-line FOLFOX. J Clin Oncol. 2009;27(15_suppl):4115.
10.
go back to reference Shitara K, Yuki S, Tahahari D, Nakamura M, Kondo C, Tsuda T, et al. Randomised phase II study comparing dose-escalated weekly paclitaxel vs standard-dose weekly paclitaxel for patients with previously treated advanced gastric cancer. Br J Cancer. 2014;110(2):271–7.CrossRefPubMed Shitara K, Yuki S, Tahahari D, Nakamura M, Kondo C, Tsuda T, et al. Randomised phase II study comparing dose-escalated weekly paclitaxel vs standard-dose weekly paclitaxel for patients with previously treated advanced gastric cancer. Br J Cancer. 2014;110(2):271–7.CrossRefPubMed
11.
go back to reference Chen Z, Chen W, Wang J, Zhu M, Zhuang Z. Pretreated baseline neutrophil count and chemotherapy-induced neutropenia may be conveniently available as prognostic biomarkers in advanced gastric cancer. Intern Med J. 2015;45(8):854–9.CrossRefPubMed Chen Z, Chen W, Wang J, Zhu M, Zhuang Z. Pretreated baseline neutrophil count and chemotherapy-induced neutropenia may be conveniently available as prognostic biomarkers in advanced gastric cancer. Intern Med J. 2015;45(8):854–9.CrossRefPubMed
12.
go back to reference Ikagawa M, Kimura M, Iwai M, Usami E, Yoshimura T, Yasuda K. Neutropenia as a prognostic factor and safety of second-line therapy with S-1 for advanced or recurrent pancreatic cancer. Mol Clin Oncol. 2016;5(3):283–8.CrossRefPubMedPubMedCentral Ikagawa M, Kimura M, Iwai M, Usami E, Yoshimura T, Yasuda K. Neutropenia as a prognostic factor and safety of second-line therapy with S-1 for advanced or recurrent pancreatic cancer. Mol Clin Oncol. 2016;5(3):283–8.CrossRefPubMedPubMedCentral
13.
go back to reference Kurihara T, Kogo M, Ishii M, Shimada K, Yoneyama K, Kitamura K, et al. Chemotherapy-induced neutropenia as a prognostic factor in patients with unresectable pancreatic cancer. Cancer Chemother Pharmacol. 2015;76(6):1217–24.CrossRefPubMed Kurihara T, Kogo M, Ishii M, Shimada K, Yoneyama K, Kitamura K, et al. Chemotherapy-induced neutropenia as a prognostic factor in patients with unresectable pancreatic cancer. Cancer Chemother Pharmacol. 2015;76(6):1217–24.CrossRefPubMed
14.
go back to reference Okuyama H, Mitsunaga S, Nakachi K, Ohno I, Shimizu S, Takahashi H, et al. Association of interleukin-6 levels and neutropenia during gemcitabine monotherapy for advanced pancreatic cancer. J Clin Oncol. 2011;29(4):178.CrossRef Okuyama H, Mitsunaga S, Nakachi K, Ohno I, Shimizu S, Takahashi H, et al. Association of interleukin-6 levels and neutropenia during gemcitabine monotherapy for advanced pancreatic cancer. J Clin Oncol. 2011;29(4):178.CrossRef
15.
go back to reference Liu R, Huang M, Zhao X, Peng W, Sun S, Cao J, et al. Neutropenia predicts better prognosis in patients with metastatic gastric cancer on a combined epirubicin, oxaliplatin and 5-fluorouracil regimen. Oncotarget. 2015;6(36):39018–27.PubMedPubMedCentral Liu R, Huang M, Zhao X, Peng W, Sun S, Cao J, et al. Neutropenia predicts better prognosis in patients with metastatic gastric cancer on a combined epirubicin, oxaliplatin and 5-fluorouracil regimen. Oncotarget. 2015;6(36):39018–27.PubMedPubMedCentral
16.
go back to reference Shitara K, Matsuo K, Takahari D, Yokota T, Shibata T, Ura T, et al. Neutropenia as a prognostic factor in advanced gastric cancer patients undergoing second-line chemotherapy with weekly paclitaxel. Ann Oncol Off J Eur Soc Med Oncol. 2010;21(12):2403–9.CrossRef Shitara K, Matsuo K, Takahari D, Yokota T, Shibata T, Ura T, et al. Neutropenia as a prognostic factor in advanced gastric cancer patients undergoing second-line chemotherapy with weekly paclitaxel. Ann Oncol Off J Eur Soc Med Oncol. 2010;21(12):2403–9.CrossRef
17.
go back to reference Konishi H, Fujiwara H, Shiozaki A, Hiramoto H, Kosuga T, Komatsu S, et al. Effects of neutropenia and histological responses in esophageal squamous cell carcinoma with neo-adjuvant chemotherapy. Int J Clin Oncol. 2016;21(1):95–101.CrossRefPubMed Konishi H, Fujiwara H, Shiozaki A, Hiramoto H, Kosuga T, Komatsu S, et al. Effects of neutropenia and histological responses in esophageal squamous cell carcinoma with neo-adjuvant chemotherapy. Int J Clin Oncol. 2016;21(1):95–101.CrossRefPubMed
18.
go back to reference Ma RM, Chen CZ, Zhang W, You J, Huang DP, Guo GL. Prognostic value of chemotherapy-induced neutropenia at the first cycle in invasive breast cancer. Medicine (Baltim). 2016;95(13):e3240.CrossRef Ma RM, Chen CZ, Zhang W, You J, Huang DP, Guo GL. Prognostic value of chemotherapy-induced neutropenia at the first cycle in invasive breast cancer. Medicine (Baltim). 2016;95(13):e3240.CrossRef
19.
go back to reference Han Y, Yu Z, Wen S, Zhang B, Cao X, Wang X. Prognostic value of chemotherapy-induced neutropenia in early-stage breast cancer. Breast Cancer Res Treat. 2012;131(2):483–90.CrossRefPubMed Han Y, Yu Z, Wen S, Zhang B, Cao X, Wang X. Prognostic value of chemotherapy-induced neutropenia in early-stage breast cancer. Breast Cancer Res Treat. 2012;131(2):483–90.CrossRefPubMed
20.
go back to reference Mitchell S, Li X, Woods M, Garcia J, Hebard-Massey K, Barron R, et al. Comparative effectiveness of granulocyte colony-stimulating factors to prevent febrile neutropenia and related complications in cancer patients in clinical practice: a systematic review. J Oncol Pharm Pract. 2016;22(5):702–16.CrossRefPubMed Mitchell S, Li X, Woods M, Garcia J, Hebard-Massey K, Barron R, et al. Comparative effectiveness of granulocyte colony-stimulating factors to prevent febrile neutropenia and related complications in cancer patients in clinical practice: a systematic review. J Oncol Pharm Pract. 2016;22(5):702–16.CrossRefPubMed
21.
go back to reference Tewari KS, Java JJ, Gatcliffe TA, Bookman MA, Monk BJ. Chemotherapy-induced neutropenia as a biomarker of survival in advanced ovarian carcinoma: an exploratory study of the gynecologic oncology group. Gynecol Oncol. 2014;133(3):439–45.CrossRefPubMed Tewari KS, Java JJ, Gatcliffe TA, Bookman MA, Monk BJ. Chemotherapy-induced neutropenia as a biomarker of survival in advanced ovarian carcinoma: an exploratory study of the gynecologic oncology group. Gynecol Oncol. 2014;133(3):439–45.CrossRefPubMed
22.
go back to reference Lee CY, Park SY, Shin TR, Park YB, Kim CH, Jang SH, et al. Early-onset neutropenia during perioperative chemotherapy is predictive of increased survival in patients with completely resected non-small cell lung cancer: a retrospective analysis. Anticancer Res. 2013;33(6):2755–61.PubMed Lee CY, Park SY, Shin TR, Park YB, Kim CH, Jang SH, et al. Early-onset neutropenia during perioperative chemotherapy is predictive of increased survival in patients with completely resected non-small cell lung cancer: a retrospective analysis. Anticancer Res. 2013;33(6):2755–61.PubMed
23.
go back to reference Jang SH, Kim SY, Kim JH, Park S, Hwang YI, Kim DG, et al. Timing of chemotherapy-induced neutropenia is a prognostic factor in patients with metastatic non-small-cell lung cancer: a retrospective analysis in gemcitabine-plus-platinum-treated patients. J Cancer Res Clin Oncol. 2013;139(3):409–17.CrossRefPubMed Jang SH, Kim SY, Kim JH, Park S, Hwang YI, Kim DG, et al. Timing of chemotherapy-induced neutropenia is a prognostic factor in patients with metastatic non-small-cell lung cancer: a retrospective analysis in gemcitabine-plus-platinum-treated patients. J Cancer Res Clin Oncol. 2013;139(3):409–17.CrossRefPubMed
24.
go back to reference Iranzo V, Sirera R, Bremnes RM, Blasco A, Jantus-Lewintre E, Taron M, et al. Chemotherapy-induced neutropenia does not correlate with DNA repair gene polymorphisms and treatment efficacy in advanced non-small-cell lung cancer patients. Clin Lung Cancer. 2011;12(4):224–30.CrossRefPubMed Iranzo V, Sirera R, Bremnes RM, Blasco A, Jantus-Lewintre E, Taron M, et al. Chemotherapy-induced neutropenia does not correlate with DNA repair gene polymorphisms and treatment efficacy in advanced non-small-cell lung cancer patients. Clin Lung Cancer. 2011;12(4):224–30.CrossRefPubMed
25.
go back to reference Di Maio M, Gridelli C, Gallo C, Shepherd F, Piantedosi FV, Cigolari S, et al. Chemotherapy-induced neutropenia and treatment efficacy in advanced non-small-cell lung cancer: a pooled analysis of three randomised trials. Lancet Oncol. 2005;6(9):669–77.CrossRefPubMed Di Maio M, Gridelli C, Gallo C, Shepherd F, Piantedosi FV, Cigolari S, et al. Chemotherapy-induced neutropenia and treatment efficacy in advanced non-small-cell lung cancer: a pooled analysis of three randomised trials. Lancet Oncol. 2005;6(9):669–77.CrossRefPubMed
26.
go back to reference Pond GR, Berry WR, Galsky MD, Wood BA, Leopold LH, Sonpavde G. Neutropenia as a potential pharmacodynamic marker for docetaxel-based chemotherapy in men with metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol. 2012;30(5_suppl):51.CrossRef Pond GR, Berry WR, Galsky MD, Wood BA, Leopold LH, Sonpavde G. Neutropenia as a potential pharmacodynamic marker for docetaxel-based chemotherapy in men with metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol. 2012;30(5_suppl):51.CrossRef
27.
go back to reference Pond GR, Berry WR, Galsky MD, Wood BA, Leopold L, Sonpavde G. Neutropenia as a potential pharmacodynamic marker for docetaxel-based chemotherapy in men with metastatic castration-resistant prostate cancer. Clin Genitourin Cancer. 2012;10(4):239–45.CrossRefPubMed Pond GR, Berry WR, Galsky MD, Wood BA, Leopold L, Sonpavde G. Neutropenia as a potential pharmacodynamic marker for docetaxel-based chemotherapy in men with metastatic castration-resistant prostate cancer. Clin Genitourin Cancer. 2012;10(4):239–45.CrossRefPubMed
28.
go back to reference Meisel A, von Felten S, Vogt DR, Liewen H, de Wit R, de Bono J, et al. Severe neutropenia during cabazitaxel treatment is associated with survival benefit in men with metastatic castration-resistant prostate cancer (mCRPC): a post-hoc analysis of the TROPIC phase III trial. Eur J Cancer. 2016;56:93–100.CrossRefPubMed Meisel A, von Felten S, Vogt DR, Liewen H, de Wit R, de Bono J, et al. Severe neutropenia during cabazitaxel treatment is associated with survival benefit in men with metastatic castration-resistant prostate cancer (mCRPC): a post-hoc analysis of the TROPIC phase III trial. Eur J Cancer. 2016;56:93–100.CrossRefPubMed
29.
go back to reference Donskov F, Michaelson MD, Puzanov I, Davis MP, Bjarnason GA, Motzer RJ, et al. Sunitinib-associated hypertension and neutropenia as efficacy biomarkers in metastatic renal cell carcinoma patients. Br J Cancer. 2015;113(11):1571–80.CrossRefPubMedPubMedCentral Donskov F, Michaelson MD, Puzanov I, Davis MP, Bjarnason GA, Motzer RJ, et al. Sunitinib-associated hypertension and neutropenia as efficacy biomarkers in metastatic renal cell carcinoma patients. Br J Cancer. 2015;113(11):1571–80.CrossRefPubMedPubMedCentral
30.
go back to reference Hashiguchi Y, Kasai M, Fukuda T, Ichimura T, Yasui T, Sumi T. Chemotherapy-induced neutropenia and febrile neutropenia in patients with gynecologic malignancy. Anticancer Drugs. 2015;26(10):1054–60.CrossRefPubMedPubMedCentral Hashiguchi Y, Kasai M, Fukuda T, Ichimura T, Yasui T, Sumi T. Chemotherapy-induced neutropenia and febrile neutropenia in patients with gynecologic malignancy. Anticancer Drugs. 2015;26(10):1054–60.CrossRefPubMedPubMedCentral
31.
go back to reference Kuboki Y, Mizunuma N, Ozaka M, Ogura M, Suenaga M, Shinozaki E, et al. Grade 3/4 neutropenia is a limiting factor in second-line FOLFIRI following FOLFOX4 failure in elderly patients with metastatic colorectal cancer. Oncol Lett. 2011;2(3):493–8.CrossRefPubMedPubMedCentral Kuboki Y, Mizunuma N, Ozaka M, Ogura M, Suenaga M, Shinozaki E, et al. Grade 3/4 neutropenia is a limiting factor in second-line FOLFIRI following FOLFOX4 failure in elderly patients with metastatic colorectal cancer. Oncol Lett. 2011;2(3):493–8.CrossRefPubMedPubMedCentral
32.
go back to reference Lee YM, Lang D, Lockwood C. Prognostic factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia: a systematic review and meta-analysis. JBI Libr Syst Rev. 2012;10(40):2593–657.PubMed Lee YM, Lang D, Lockwood C. Prognostic factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia: a systematic review and meta-analysis. JBI Libr Syst Rev. 2012;10(40):2593–657.PubMed
33.
go back to reference Weycker D, Li X, Edelsberg J, Barron R, Kartashov A, Xu H, et al. Risk and consequences of chemotherapy-induced febrile neutropenia in patients with metastatic solid tumors. J Oncol Pract. 2015;11(1):47–54.CrossRefPubMed Weycker D, Li X, Edelsberg J, Barron R, Kartashov A, Xu H, et al. Risk and consequences of chemotherapy-induced febrile neutropenia in patients with metastatic solid tumors. J Oncol Pract. 2015;11(1):47–54.CrossRefPubMed
34.
go back to reference Kalinka-Warzocha E, Plazas JG, Mineur L, Salek T, Hendlisz A, DeCosta L, et al. Chemotherapy treatment patterns and neutropenia management in gastric cancer. Gastric Cancer. 2015;18(2):360–7.CrossRefPubMed Kalinka-Warzocha E, Plazas JG, Mineur L, Salek T, Hendlisz A, DeCosta L, et al. Chemotherapy treatment patterns and neutropenia management in gastric cancer. Gastric Cancer. 2015;18(2):360–7.CrossRefPubMed
35.
go back to reference Watanabe H, Ikesue H, Oshiro M, Nagata K, Mishima K, Takada A, et al. Risk factors for predicting severe neutropenia induced by amrubicin in patients with advanced lung cancer. Chemotherapy. 2012;58(6):419–25.CrossRefPubMed Watanabe H, Ikesue H, Oshiro M, Nagata K, Mishima K, Takada A, et al. Risk factors for predicting severe neutropenia induced by amrubicin in patients with advanced lung cancer. Chemotherapy. 2012;58(6):419–25.CrossRefPubMed
36.
go back to reference Cortejoso L, Garcia-Gonzalez X, Garcia MI, Garcia-Alfonso P, Sanjurjo M, Lopez-Fernandez LA. Cost-effectiveness of screening for DPYD polymorphisms to prevent neutropenia in cancer patients treated with fluoropyrimidines. Pharmacogenomics. 2016;17(9):979–84.CrossRefPubMed Cortejoso L, Garcia-Gonzalez X, Garcia MI, Garcia-Alfonso P, Sanjurjo M, Lopez-Fernandez LA. Cost-effectiveness of screening for DPYD polymorphisms to prevent neutropenia in cancer patients treated with fluoropyrimidines. Pharmacogenomics. 2016;17(9):979–84.CrossRefPubMed
37.
go back to reference Patel SM, Chan J, Hui RL, Spence MM. Evaluation of the role of UGT1A1 genotype testing in colorectal cancer patients administered irinotecan and the occurence of grade 3 and 4 neutropenia. J Clin Oncol. 2012;30(4_suppl):412.CrossRef Patel SM, Chan J, Hui RL, Spence MM. Evaluation of the role of UGT1A1 genotype testing in colorectal cancer patients administered irinotecan and the occurence of grade 3 and 4 neutropenia. J Clin Oncol. 2012;30(4_suppl):412.CrossRef
38.
go back to reference Hazama S, Okuyama Y, Kato T, Okayama N, Hinoda Y, Sakamoto J, et al. Use of genotype subset selections of multi-UGT1As polymorphisms to predict severe neutropenia and tumor responses of metastatic CRC patients received FOLFIRI regimen. J Clin Oncol. 2009;27(15_suppl):e15038. Hazama S, Okuyama Y, Kato T, Okayama N, Hinoda Y, Sakamoto J, et al. Use of genotype subset selections of multi-UGT1As polymorphisms to predict severe neutropenia and tumor responses of metastatic CRC patients received FOLFIRI regimen. J Clin Oncol. 2009;27(15_suppl):e15038.
39.
go back to reference Atasilp C, Chansriwong P, Sirachainan E, Reungwetwattana T, Chamnanphon M, Puangpetch A, et al. Correlation of UGT1A1(*)28 and (*)6 polymorphisms with irinotecan-induced neutropenia in Thai colorectal cancer patients. Drug Metab Pharmacokinet. 2016;31(1):90–4.CrossRefPubMed Atasilp C, Chansriwong P, Sirachainan E, Reungwetwattana T, Chamnanphon M, Puangpetch A, et al. Correlation of UGT1A1(*)28 and (*)6 polymorphisms with irinotecan-induced neutropenia in Thai colorectal cancer patients. Drug Metab Pharmacokinet. 2016;31(1):90–4.CrossRefPubMed
41.
go back to reference Uchiyama T, Kanno H, Ishitani K, Fujii H, Ohta H, Matsui H, et al. An SNP in CYP39A1 is associated with severe neutropenia induced by docetaxel. Cancer Chemother Pharmacol. 2012;69(6):1617–24.CrossRefPubMed Uchiyama T, Kanno H, Ishitani K, Fujii H, Ohta H, Matsui H, et al. An SNP in CYP39A1 is associated with severe neutropenia induced by docetaxel. Cancer Chemother Pharmacol. 2012;69(6):1617–24.CrossRefPubMed
42.
go back to reference Nieuweboer AJ, Smid M, de Graan AJ, Elbouazzaoui S, de Bruijn P, Martens JW, et al. Predicting paclitaxel-induced neutropenia using the DMET platform. Pharmacogenomics. 2015;16(11):1231–41.CrossRefPubMed Nieuweboer AJ, Smid M, de Graan AJ, Elbouazzaoui S, de Bruijn P, Martens JW, et al. Predicting paclitaxel-induced neutropenia using the DMET platform. Pharmacogenomics. 2015;16(11):1231–41.CrossRefPubMed
43.
go back to reference Ichikawa W, Uehara K, Minamimura K, Tanaka C, Takii Y, Miyauchi H, et al. An internally and externally validated nomogram for predicting the risk of irinotecan-induced severe neutropenia in advanced colorectal cancer patients. Br J Cancer. 2015;112(10):1709–16.CrossRefPubMedPubMedCentral Ichikawa W, Uehara K, Minamimura K, Tanaka C, Takii Y, Miyauchi H, et al. An internally and externally validated nomogram for predicting the risk of irinotecan-induced severe neutropenia in advanced colorectal cancer patients. Br J Cancer. 2015;112(10):1709–16.CrossRefPubMedPubMedCentral
44.
go back to reference Lewis LD, Miller AA, Owzar K, Bies RR, Markova S, Jiang C, et al. The relationship of polymorphisms in ABCC2 and SLCO1B3 with docetaxel pharmacokinetics and neutropenia: CALGB 60805 (Alliance). Pharmacogenet Genom. 2013;23(1):29–33.CrossRef Lewis LD, Miller AA, Owzar K, Bies RR, Markova S, Jiang C, et al. The relationship of polymorphisms in ABCC2 and SLCO1B3 with docetaxel pharmacokinetics and neutropenia: CALGB 60805 (Alliance). Pharmacogenet Genom. 2013;23(1):29–33.CrossRef
45.
go back to reference Tang NL, Liao CD, Wang X, Mo FK, Chan VT, Ng R, et al. Role of pharmacogenetics on adjuvant chemotherapy-induced neutropenia in Chinese breast cancer patients. J Cancer Res Clin Oncol. 2013;139(3):419–27.CrossRefPubMed Tang NL, Liao CD, Wang X, Mo FK, Chan VT, Ng R, et al. Role of pharmacogenetics on adjuvant chemotherapy-induced neutropenia in Chinese breast cancer patients. J Cancer Res Clin Oncol. 2013;139(3):419–27.CrossRefPubMed
46.
go back to reference Tsuji D, Ikeda M, Yamamoto K, Nakamori H, Kim YI, Kawasaki Y, et al. Drug-related genetic polymorphisms affecting severe chemotherapy-induced neutropenia in breast cancer patients: a hospital-based observational study. Medicine (Baltim). 2016;95(44):e5151.CrossRef Tsuji D, Ikeda M, Yamamoto K, Nakamori H, Kim YI, Kawasaki Y, et al. Drug-related genetic polymorphisms affecting severe chemotherapy-induced neutropenia in breast cancer patients: a hospital-based observational study. Medicine (Baltim). 2016;95(44):e5151.CrossRef
47.
go back to reference Laskey RA, Poniewierski MS, Lopez MA, Hanna RK, Secord AA, Gehrig PA, et al. Predictors of severe and febrile neutropenia during primary chemotherapy for ovarian cancer. Gynecol Oncol. 2012;125(3):625–30.CrossRefPubMed Laskey RA, Poniewierski MS, Lopez MA, Hanna RK, Secord AA, Gehrig PA, et al. Predictors of severe and febrile neutropenia during primary chemotherapy for ovarian cancer. Gynecol Oncol. 2012;125(3):625–30.CrossRefPubMed
49.
go back to reference Ikesue H, Watanabe H, Hirano M, Chikamori A, Suetsugu K, Ryokai Y, et al. Risk factors for predicting severe neutropenia induced by pemetrexed plus carboplatin therapy in patients with advanced non-small cell lung cancer. Biol Pharm Bull. 2015;38(8):1192–8.CrossRefPubMed Ikesue H, Watanabe H, Hirano M, Chikamori A, Suetsugu K, Ryokai Y, et al. Risk factors for predicting severe neutropenia induced by pemetrexed plus carboplatin therapy in patients with advanced non-small cell lung cancer. Biol Pharm Bull. 2015;38(8):1192–8.CrossRefPubMed
50.
go back to reference Yano R, Konno A, Watanabe K, Tsukamoto H, Kayano Y, Ohnaka H, et al. Pharmacoethnicity of docetaxel-induced severe neutropenia: integrated analysis of published phase II and III trials. Int J Clin Oncol. 2013;18(1):96–104.CrossRefPubMed Yano R, Konno A, Watanabe K, Tsukamoto H, Kayano Y, Ohnaka H, et al. Pharmacoethnicity of docetaxel-induced severe neutropenia: integrated analysis of published phase II and III trials. Int J Clin Oncol. 2013;18(1):96–104.CrossRefPubMed
51.
go back to reference Shigeta K, Kosaka T, Yazawa S, Yasumizu Y, Mizuno R, Nagata H, et al. Predictive factors for severe and febrile neutropenia during docetaxel chemotherapy for castration-resistant prostate cancer. Int J Clin Oncol. 2015;20(3):605–12.CrossRefPubMed Shigeta K, Kosaka T, Yazawa S, Yasumizu Y, Mizuno R, Nagata H, et al. Predictive factors for severe and febrile neutropenia during docetaxel chemotherapy for castration-resistant prostate cancer. Int J Clin Oncol. 2015;20(3):605–12.CrossRefPubMed
52.
go back to reference Gupta V, Kumar V, Singh SK. Low vitamin D levels are associated with an adverse clinical outcome in febrile neutropenia. J Pediatr Hematol Oncol. 2016;38(3):202–4.CrossRefPubMed Gupta V, Kumar V, Singh SK. Low vitamin D levels are associated with an adverse clinical outcome in febrile neutropenia. J Pediatr Hematol Oncol. 2016;38(3):202–4.CrossRefPubMed
53.
go back to reference O’Malley M, Healy P, Daignault S, Ramnath N. Cigarette smoking and gemcitabine-induced neutropenia in advanced solid tumors. Oncology. 2013;85(4):216–22.CrossRefPubMedPubMedCentral O’Malley M, Healy P, Daignault S, Ramnath N. Cigarette smoking and gemcitabine-induced neutropenia in advanced solid tumors. Oncology. 2013;85(4):216–22.CrossRefPubMedPubMedCentral
54.
go back to reference Sato I, Nakaya N, Shimasaki T, Nakajima H, Motoo Y. Prediction of docetaxel monotherapy-induced neutropenia based on the monocyte percentage. Oncol Lett. 2012;3(4):860–4.PubMedPubMedCentral Sato I, Nakaya N, Shimasaki T, Nakajima H, Motoo Y. Prediction of docetaxel monotherapy-induced neutropenia based on the monocyte percentage. Oncol Lett. 2012;3(4):860–4.PubMedPubMedCentral
55.
go back to reference Lyman GH, Abella E, Pettengell R. Risk factors for febrile neutropenia among patients with cancer receiving chemotherapy: a systematic review. Crit Rev Oncol Hematol. 2014;90(3):190–9.CrossRefPubMed Lyman GH, Abella E, Pettengell R. Risk factors for febrile neutropenia among patients with cancer receiving chemotherapy: a systematic review. Crit Rev Oncol Hematol. 2014;90(3):190–9.CrossRefPubMed
56.
go back to reference Dinan MA, Hirsch BR, Lyman GH. Management of chemotherapy-induced neutropenia: measuring quality, cost, and value. J Natl Compr Canc Netw. 2015;13(1):e1–7.CrossRefPubMed Dinan MA, Hirsch BR, Lyman GH. Management of chemotherapy-induced neutropenia: measuring quality, cost, and value. J Natl Compr Canc Netw. 2015;13(1):e1–7.CrossRefPubMed
57.
go back to reference Yoshida Y, Hoshino S, Aisu N, Mogi A, Yamada T, Kojima D, et al. Can grade 2 neutropenia predict the risk of grade 3 neutropenia in metastatic colorectal cancer patients treated with chemotherapy? Support Care Cancer. 2015;23(6):1623–7.CrossRefPubMed Yoshida Y, Hoshino S, Aisu N, Mogi A, Yamada T, Kojima D, et al. Can grade 2 neutropenia predict the risk of grade 3 neutropenia in metastatic colorectal cancer patients treated with chemotherapy? Support Care Cancer. 2015;23(6):1623–7.CrossRefPubMed
58.
go back to reference Chiarotto JA, Dranitsaris G. Full-dose chemotherapy in early stage breast cancer regardless of absolute neutrophil count and without G-CSF does not increase chemotherapy-induced febrile neutropenia. Support Care Cancer. 2013;21(10):2727–31.CrossRefPubMed Chiarotto JA, Dranitsaris G. Full-dose chemotherapy in early stage breast cancer regardless of absolute neutrophil count and without G-CSF does not increase chemotherapy-induced febrile neutropenia. Support Care Cancer. 2013;21(10):2727–31.CrossRefPubMed
59.
go back to reference Pinter T, Klippel Z, Cesas A, Croitoru A, Decaestecker J, Gibbs P, et al. A phase III, randomized, double-blind, placebo-controlled trial of pegfilgrastim in patients receiving first-line FOLFOX/bevacizumab or FOLFIRI/bevacizumab for locally advanced or metastatic colorectal cancer: final results of the pegfilgrastim and anti-VEGF evaluation study (PAVES). Clin Colorectal Cancer. 2017;16(2):103–114.e3. https://doi.org/10.1016/j.clcc.2016.08.008.CrossRefPubMed Pinter T, Klippel Z, Cesas A, Croitoru A, Decaestecker J, Gibbs P, et al. A phase III, randomized, double-blind, placebo-controlled trial of pegfilgrastim in patients receiving first-line FOLFOX/bevacizumab or FOLFIRI/bevacizumab for locally advanced or metastatic colorectal cancer: final results of the pegfilgrastim and anti-VEGF evaluation study (PAVES). Clin Colorectal Cancer. 2017;16(2):103–114.e3. https://​doi.​org/​10.​1016/​j.​clcc.​2016.​08.​008.CrossRefPubMed
60.
go back to reference Barron R, Michels SL, Reynolds MW, Tomic K, Yu J, Lyman G. Risk of mortality in patients with cancer experiencing febrile neutropenia. J Clin Oncol. 2009;27(15_suppl):9561. Barron R, Michels SL, Reynolds MW, Tomic K, Yu J, Lyman G. Risk of mortality in patients with cancer experiencing febrile neutropenia. J Clin Oncol. 2009;27(15_suppl):9561.
61.
go back to reference Lal A, Kumar P, Bhurgri Y, Rizvi N, Shaikh AJ, Adil S, et al. Factors influencing in-hospital length of stay and mortality in cancer patients suffering from febrile neutropenia. J Clin Oncol. 2009;27(15_suppl):e20716. Lal A, Kumar P, Bhurgri Y, Rizvi N, Shaikh AJ, Adil S, et al. Factors influencing in-hospital length of stay and mortality in cancer patients suffering from febrile neutropenia. J Clin Oncol. 2009;27(15_suppl):e20716.
62.
go back to reference Bouteloup M, Perinel S, Bourmaud A, Azoulay E, Mokart D, Darmon M. Outcomes in adult critically Ill cancer patients with and without neutropenia: a systematic review and meta-analysis of the Groupe de Recherche en Reanimation Respiratoire du patient d’Onco-Hematologie (GRRR-OH). Oncotarget. 2017;8(1):1860–70. https://doi.org/10.18632/oncotarget.12165.CrossRefPubMed Bouteloup M, Perinel S, Bourmaud A, Azoulay E, Mokart D, Darmon M. Outcomes in adult critically Ill cancer patients with and without neutropenia: a systematic review and meta-analysis of the Groupe de Recherche en Reanimation Respiratoire du patient d’Onco-Hematologie (GRRR-OH). Oncotarget. 2017;8(1):1860–70. https://​doi.​org/​10.​18632/​oncotarget.​12165.CrossRefPubMed
64.
go back to reference Chohan K, Lai D, McNamara M, Grogan L, Breathnach OS. The frequency of febrile neutropenia in oncology patients receiving chemotherapy. J Clin Oncol. 2009;27(15_suppl):e20691. Chohan K, Lai D, McNamara M, Grogan L, Breathnach OS. The frequency of febrile neutropenia in oncology patients receiving chemotherapy. J Clin Oncol. 2009;27(15_suppl):e20691.
65.
go back to reference Chia VM, Page JH, Rodriguez R, Yang SJ, Huynh J, Chao C. Chronic comorbid conditions associated with risk of febrile neutropenia in breast cancer patients treated with chemotherapy. Breast Cancer Res Treat. 2013;138(2):621–31.CrossRefPubMed Chia VM, Page JH, Rodriguez R, Yang SJ, Huynh J, Chao C. Chronic comorbid conditions associated with risk of febrile neutropenia in breast cancer patients treated with chemotherapy. Breast Cancer Res Treat. 2013;138(2):621–31.CrossRefPubMed
66.
go back to reference Chan A, Lee CP, Chiang J, Ng R. Breakthrough febrile neutropenia and associated complications among elderly cancer patients receiving myelosuppressive chemotherapy for solid tumors and lymphomas. Support Care Cancer. 2013;21(8):2137–43.CrossRefPubMed Chan A, Lee CP, Chiang J, Ng R. Breakthrough febrile neutropenia and associated complications among elderly cancer patients receiving myelosuppressive chemotherapy for solid tumors and lymphomas. Support Care Cancer. 2013;21(8):2137–43.CrossRefPubMed
67.
go back to reference Li X, Luthra R, Morrow PK, Fisher MD, Reiner M, Barron RL, et al. Comorbidities among patients with cancer who do and do not develop febrile neutropenia during the first chemotherapy cycle. J Oncol Pharm Pract. 2016;22(5):679–89.CrossRefPubMed Li X, Luthra R, Morrow PK, Fisher MD, Reiner M, Barron RL, et al. Comorbidities among patients with cancer who do and do not develop febrile neutropenia during the first chemotherapy cycle. J Oncol Pharm Pract. 2016;22(5):679–89.CrossRefPubMed
68.
go back to reference Ozguroglu M, Oudard S, Sartor AO, Hansen S, Machiels JH, Shen L, et al. Effect of G-CSF prophylaxis on the occurrence of neutropenia in men receiving cabazitaxel plus prednisone for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in the TROPIC study. J Clin Oncol. 2011;29(7):144.CrossRef Ozguroglu M, Oudard S, Sartor AO, Hansen S, Machiels JH, Shen L, et al. Effect of G-CSF prophylaxis on the occurrence of neutropenia in men receiving cabazitaxel plus prednisone for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in the TROPIC study. J Clin Oncol. 2011;29(7):144.CrossRef
69.
go back to reference Dienstmann R, Brana I, Rodon J, Tabernero J. Toxicity as a biomarker of efficacy of molecular targeted therapies: focus on EGFR and VEGF inhibiting anticancer drugs. Oncologist. 2011;16(12):1729–40.CrossRefPubMedPubMedCentral Dienstmann R, Brana I, Rodon J, Tabernero J. Toxicity as a biomarker of efficacy of molecular targeted therapies: focus on EGFR and VEGF inhibiting anticancer drugs. Oncologist. 2011;16(12):1729–40.CrossRefPubMedPubMedCentral
70.
go back to reference Fukae M, Shiraishi Y, Hirota T, Sasaki Y, Yamahashi M, Takayama K, et al. Population pharmacokinetic-pharmacodynamic modeling and model-based prediction of docetaxel-induced neutropenia in Japanese patients with non-small cell lung cancer. Cancer Chemother Pharmacol. 2016;78(5):1013–23.CrossRefPubMed Fukae M, Shiraishi Y, Hirota T, Sasaki Y, Yamahashi M, Takayama K, et al. Population pharmacokinetic-pharmacodynamic modeling and model-based prediction of docetaxel-induced neutropenia in Japanese patients with non-small cell lung cancer. Cancer Chemother Pharmacol. 2016;78(5):1013–23.CrossRefPubMed
72.
go back to reference Huang K, Luo A, Li X, Li S, Wang S. Chemotherapy-induced neutropenia during adjuvant treatment for cervical cancer patients: development and validation of a prediction model. Int J Clin Exp Med. 2015;8(7):10835–44.PubMedPubMedCentral Huang K, Luo A, Li X, Li S, Wang S. Chemotherapy-induced neutropenia during adjuvant treatment for cervical cancer patients: development and validation of a prediction model. Int J Clin Exp Med. 2015;8(7):10835–44.PubMedPubMedCentral
73.
go back to reference Lyman GH, Lyman CH, Agboola O. Risk models for predicting chemotherapy-induced neutropenia. Oncologist. 2005;10(6):427–37.CrossRefPubMed Lyman GH, Lyman CH, Agboola O. Risk models for predicting chemotherapy-induced neutropenia. Oncologist. 2005;10(6):427–37.CrossRefPubMed
74.
go back to reference Nieuweboer AJ, Smid M, de Graan AM, Elbouazzaoui S, de Bruijn P, Eskens FA, et al. Role of genetic variation in docetaxel-induced neutropenia and pharmacokinetics. Pharmacogenom J. 2016;16(6):519–24.CrossRef Nieuweboer AJ, Smid M, de Graan AM, Elbouazzaoui S, de Bruijn P, Eskens FA, et al. Role of genetic variation in docetaxel-induced neutropenia and pharmacokinetics. Pharmacogenom J. 2016;16(6):519–24.CrossRef
75.
go back to reference Charehbili A, de Groot S, van der Straaten T, Swen JJ, Pijl H, Gelderblom H, et al. Exploratory analysis of candidate germline gene polymorphisms in breast cancer patients treated with neoadjuvant anthracycline-containing chemotherapy and associations with febrile neutropenia. Pharmacogenomics. 2015;16(11):1267–76.CrossRefPubMed Charehbili A, de Groot S, van der Straaten T, Swen JJ, Pijl H, Gelderblom H, et al. Exploratory analysis of candidate germline gene polymorphisms in breast cancer patients treated with neoadjuvant anthracycline-containing chemotherapy and associations with febrile neutropenia. Pharmacogenomics. 2015;16(11):1267–76.CrossRefPubMed
76.
go back to reference Wang L, Chen YZ, Shi D, Shi XY, Zou Z, Zhao JH. Incidence and risk of severe neutropenia in advanced cancer patients treated with cetuximab: a meta-analysis. Drugs R D. 2011;11(4):317–26.CrossRefPubMed Wang L, Chen YZ, Shi D, Shi XY, Zou Z, Zhao JH. Incidence and risk of severe neutropenia in advanced cancer patients treated with cetuximab: a meta-analysis. Drugs R D. 2011;11(4):317–26.CrossRefPubMed
77.
go back to reference Patel M, Palani S, Chakravarty A, Yang J, Shyu WC, Mettetal JT. Dose schedule optimization and the pharmacokinetic driver of neutropenia. PLoS One. 2014;9(10):e109892.CrossRefPubMedPubMedCentral Patel M, Palani S, Chakravarty A, Yang J, Shyu WC, Mettetal JT. Dose schedule optimization and the pharmacokinetic driver of neutropenia. PLoS One. 2014;9(10):e109892.CrossRefPubMedPubMedCentral
78.
go back to reference Kouranos V, Dimopoulos G, Vassias A, Syrigos KN. Chemotherapy-induced neutropenia in lung cancer patients: the role of antibiotic prophylaxis. Cancer Lett. 2011;313(1):9–14.CrossRefPubMed Kouranos V, Dimopoulos G, Vassias A, Syrigos KN. Chemotherapy-induced neutropenia in lung cancer patients: the role of antibiotic prophylaxis. Cancer Lett. 2011;313(1):9–14.CrossRefPubMed
Metadata
Title
Chemotherapy-Induced Neutropenia as a Prognostic and Predictive Marker of Outcomes in Solid-Tumor Patients
Authors
Pashtoon Murtaza Kasi
Axel Grothey
Publication date
01-05-2018
Publisher
Springer International Publishing
Published in
Drugs / Issue 7/2018
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI
https://doi.org/10.1007/s40265-018-0909-3

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