Abstract
Purpose
Myelosuppression induced by concurrent chemotherapy and radiotherapy can be a significant problem in patients with non-small cell lung cancer (NSCLC), but its risk factors remain largely unknown. The objective of this study was to retrospectively evaluate clinical data obtained before chemoradiotherapy (CRT) to identify the risk factors for myelosuppression in patients with advanced NSCLC.
Methods
Between January 2007 and January 2012, 141 patients with advanced NSCLC were treated with curative intent according to the CRT protocol (50–70 Gy at 2 Gy/day with paclitaxel 135–175 mg/m2 and carboplatin 100 mg/m2 on days 1, 22, and 43). The endpoint of this survey was the occurrence of grade 3 or higher myelosuppression (neutropenia, leukopenia, thrombocytopenia, or anemia). Risk factors significantly related to myelosuppression were extracted using logistic regression analysis.
Results
Grade 3 or higher neutropenia, leukopenia, thrombocytopenia, or anemia occurred in 19.9, 16.3, 14.9, and 0 % of the patients, respectively. According to the multivariate analysis, the risk factors included age, albumin, and body surface area (BSA) for neutropenia; performance status and bone metastases for leukopenia; and age, gender, and serum creatinine concentration for thrombocytopenia (p < 0.05).
Conclusions
It was found that age, BSA, creatinine level, and female gender were the most important factors for CRT-induced myelosuppression in advanced NSCLC. By identifying these risk factors, medical staff can improve application of appropriate medical care to reduce the myelosuppression in advanced NSCLC patients treated by CRT.
References
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T et al (2008) Cancer statistics, 2008. CA Cancer J Clin 58:71–96
Dillman RO, Herndon J, Seagren SL, Eaton WJ, Green MR (1996) Improved survival in stage III non-small-cell lung cancer: seven-year follow-up of cancer and leukemia group B (CALGB) 8433 trial. J Natl Cancer Inst 88:1210–1215
Fournel P, Robinet G, Thomas P, Souquet PJ, Lena H, Vergnenegre A et al (2005) Randomized phase III trial of sequential chemoradiotherapy compared with concurrent chemoradiotherapy in locally advanced non-small-cell lung cancer: Groupe Lyon-Saint-Etienne d'Oncologie Thoracique-Groupe Francais de Pneumo-Cancerologie NPC 95-01 Study. J Clin Oncol 23:5910–5917
Rakovitch E, Tsao M, Ung Y, Pignol JP, Cheung P, Chow E (2004) Comparison of the efficacy and acute toxicity of weekly versus daily chemoradiotherapy for non-small-cell lung cancer: a meta-analysis. Int J Radiat Oncol Biol Phys 58:196–203
Pritchard RS, Anthony SP (1996) Chemotherapy plus radiotherapy compared with radiotherapy alone in the treatment of locally advanced, unresectable, non-small-cell lung cancer: a meta-analysis. Ann Intern Med 125:723–729
Zatloukal P, Petruzelka L, Zemanova M, Havel L, Janku F, Judas L et al (2004) Concurrent versus sequential chemoradiotherapy with cisplatin and vinorelbine in locally advanced non-small cell lung cancer: a randomized study. Lung Cancer 46:87–98
Li J, Dai CH, Shi SB, Bao QL, Yu LC, Wu JR (2010) Induction concurrent chemoradiotherapy compared with induction radiotherapy for superior sulcus non-small cell lung cancer: a retrospective study. Asia Pac J Clin Oncol 6:57–65
Abdelwahab S, Abdulla H, Azmy A, Abdelfatah A, Abdel-Aziz H, Margerges M et al (2009) Integration of irinotecan and cisplatin with early concurrent conventional radiotherapy for limited-disease SCLC (LD-SCLC). Int J Clin Oncol 14:230–236
Sunpaweravong P, Magree L, Rabinovitch R, Bunn P, Kelly K (2006) A phase I/II study of docetaxel, etoposide, and carboplatin before concurrent chemoradiotherapy with cisplatin and etoposide in limited-stage small cell lung cancer. Invest New Drugs 24:213–221
Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, Curran WJ (2005) Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol 23:5883–5891
Cox JD, Pajak TF, Asbell S, Russell AH, Pederson J, Byhardt RW et al (1993) Interruptions of high-dose radiation therapy decrease long-term survival of favorable patients with unresectable non-small cell carcinoma of the lung: analysis of 1244 cases from 3 Radiation Therapy Oncology Group (RTOG) trials. Int J Radiat Oncol Biol Phys 27:493–498
Herrmann T (1994) Interruptions of high-dose radiation therapy decrease the long-term survival of favorable patients with unresectable non-small-cell carcinoma of the lung. Analysis of 1244 cases from radio-oncology (RTOG) studies. Radiation Therapy Oncology Group. Strahlenther Onkol 170:551–552
Choi CW, Sung HJ, Park KH, Yoon SY, Kim SJ, Oh SC et al (2003) Early lymphopenia as a risk factor for chemotherapy-induced febrile neutropenia. Am J Hematol 73:263–266
Kuderer NM, Dale DC, Crawford J, Cosler LE, Lyman GH (2006) Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer 106:2258–2266
Hui EP, Leung LK, Poon TC, Mo F, Chan VT, Ma AT et al (2011) Prediction of outcome in cancer patients with febrile neutropenia: a prospective validation of the Multinational Association for Supportive Care in Cancer risk index in a Chinese population and comparison with the Talcott model and artificial neural network. Support Care Cancer 19:1625–1635
Morrison VMV, Picozzi VPV, Scott SSS, Pohlman BPB, Dickman EDE, Lee MLM et al (2001) The impact of age on delivered dose intensity and hospitalizations for febrile neutropenia in patients with intermediate-grade non-Hodgkin's lymphoma receiving initial CHOP chemotherapy: a risk factor analysis. Clin Lymphoma 2:47–56
Lyman GLG, Lyman CLC, Agboola OAO (2005) Risk models for predicting chemotherapy-induced neutropenia. Oncologist 10:427–437
Arrieta O, Michel OR, Villanueva-Rodriguez G, Serna-Thome MG, Flores-Estrada D, Diaz-Romero C et al (2010) Association of nutritional status and serum albumin levels with development of toxicity in patients with advanced non-small cell lung cancer treated with paclitaxel-cisplatin chemotherapy: a prospective study. BMC Cancer 10:1–7
Ishizuka M, Fujimoto Y, Itoh Y, Kitagawa K, Sano M, Miyagawa Y et al (2011) Relationship between hematotoxicity and serum albumin level in the treatment of head and neck cancers with concurrent chemoradiotherapy using cisplatin. Jpn J Clin Oncol 41:973–979
Alexandre J, Gross-Goupil M, Falissard B, Nguyen ML, Gornet JM, Misset JL et al (2003) Evaluation of the nutritional and inflammatory status in cancer patients for the risk assessment of severe haematological toxicity following chemotherapy. Ann Oncol 14:36–41
Intragumtornchai TIT, Sutheesophon JSJ, Sutcharitchan PSP, Swasdikul DSD (2000) A predictive model for life-threatening neutropenia and febrile neutropenia after the first course of CHOP chemotherapy in patients with aggressive non-Hodgkin's lymphoma. Leuk Lymphoma 37:351–360
Kratz F, Ehling G, Kauffmann HM, Unger C (2007) Acute and repeat-dose toxicity studies of the (6-maleimidocaproyl)hydrazone derivative of doxorubicin (DOXO-EMCH), an albumin-binding prodrug of the anticancer agent doxorubicin. Hum Exp Toxicol 26:19–35
Singh S, Parulekar W, Murray N, Feld R, Evans WK, Tu D et al (2005) Influence of sex on toxicity and treatment outcome in small-cell lung cancer. J Clin Oncol 23:850–856
Bruno RBR, Hille DHD, Riva ARA, Vivier NVN, Huinnink WHW et al (1998) Population pharmacokinetics/pharmacodynamics of docetaxel in phase II studies in patients with cancer. J Clin Oncol 16:187–196
Lambert LA, Armstrong TS, Lee JJ, Liu S, Katz MH, Eng C et al (2009) Incidence, risk factors, and impact of severe neutropenia after hyperthermic intraperitoneal mitomycin C. Ann Surg Oncol 16:2181–2187
Kantarjian H, Giles F, List A, Lyons R, Sekeres MA, Pierce S et al (2007) The incidence and impact of thrombocytopenia in myelodysplastic syndromes. Cancer 109(9):1705–1714
Liou SY, Stephens JM, Carpiuc KT, Feng W, Botteman MF, Hay JW (2007) Economic burden of haematological adverse effects in cancer patients: a systematic review. Clin Drug Investig 27:381–396
Stinchcombe TE, Choi J, Schell MJ, Mears A, Jones PE, Nachtsheim RV et al (2006) Carboplatin-based chemotherapy in patients with advanced non-small cell lung cancer and a poor performance status. Lung Cancer 2:237–243
Gridelli C, Ardizzoni A, Le Chevalier T, Manegold C, Perrone F, Thatcher N et al (2004) Treatment of advanced non-small-cell lung cancer patients with ECOG performance status 2: results of an European Experts Panel. Ann Oncol 15:419–426
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET et al (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649–655
Armstrong TS, Cao Y, Scheurer ME, Vera-Bolanos E, Manning R, Okcu MF et al (2009) Risk analysis of severe myelotoxicity with temozolomide: the effects of clinical and genetic factors. Neuro Oncol 11:825–832
Kogo M, Watahiki M, Sunaga T, Kaneko K, Yoneyama K, Imawari M et al (2011) Analysis of the risk factors for myelosuppression after chemoradiotherapy involving 5-fluorouracil and platinum for patients with esophageal cancer. Hepatogastroenterology 58:802–808
Holoye PY, Kalbfleisch J (1984) The influence of myelosuppression on the response to chemotherapy in small cell bronchogenic carcinoma. Cancer 54:411–415
Nalesnik JG, Mysliwiec AG, Canby-Hagino E (2004) Anemia in men with advanced prostate cancer: incidence, etiology, and treatment. Rev Urol 6:1–4
Khafagy R, Shackley D, Samuel J, O’Flynn K, Betts C, Clarke N (2007) Complications arising in the final year of life in men dying from advanced prostate cancer. J Palliat Med 10:705–711
Elting LS, Rubenstein EB, Martin CG, Kurtin D, Rodriguez S, Laiho E et al (2001) Incidence, cost, and outcomes of bleeding and chemotherapy dose modification among solid tumor patients with chemotherapy-induced thrombocytopenia. J Clin Oncol 19:1137–1146
Mac MM, Lamborn K, Khan W, Varghese A, Graef L, Knox S (1997) Radiotherapy-associated neutropenia and thrombocytopenia: analysis of risk factors and development of a predictive model. Blood 89:2303–2310
Hefti FF, Bales R (2006) Regulatory issues in aging pharmacology. Aging Cell 5:3–8
Massacesi C, Marcucci F, Rocchi MB, Mazzanti P, Pilone A, Bonsignori M (2004) Factors predicting docetaxel-related toxicity: experience at a single institution. J Chemother 16:86–93
Matsui K, Masuda N, Uchida Y, Fukuoka M, Negoro S, Yana T et al (1996) Determinants of myelosuppression in the treatment of non-small cell lung cancer with cisplatin-containing chemotherapy. Jpn J Cancer Res 87:781–786
Sloan JA, Goldberg RM, Sargent DJ, Vargas-Chanes D, Nair S, Cha SS et al (2002) Women experience greater toxicity with fluorouracil-based chemotherapy for colorectal cancer. J Clin Oncol 20:1491–1498
Armstrong TS, Cao Y, Scheurer ME, Vera-Bolanos E, Manning R, Okcu MF et al (2009) Risk analysis of severe myelotoxicity with temozolomide: the effects of clinical and genetic factors. Neuro Oncol 11:825–832
Anderson GD (2008) Gender differences in pharmacological response. Int Rev Neurobiol 83:1–10
Kloft C, Wallin J, Henningsson A, Chatelut E, Karlsson MO (2006) Population pharmacokinetic pharmacodynamic model for neutropenia with patient subgroup identification: comparison across anticancer drugs. Clin Cancer Res 12:5481–5490
Hurria A, Hurria A, Brogan K, Panageas KS, Pearce C, Norton L et al (2005) Effect of creatinine clearance on patterns of toxicity in older patients receiving adjuvant chemotherapy for breast cancer. Drugs Aging 22:785–791
Acknowledgments
We express our thanks to the staff of the Radiotherapy Department and Medical Record Room of Tianjin Medical University Cancer Hospital for their support in data collection. This study was funded by Tianjin Medical University Graduated Research.
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The authors declare no conflict of interest.
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Jiang, N., Chen, XC. & Zhao, Y. Analysis of the risk factors for myelosuppression after concurrent chemoradiotherapy for patients with advanced non-small cell lung cancer. Support Care Cancer 21, 785–791 (2013). https://doi.org/10.1007/s00520-012-1580-y
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DOI: https://doi.org/10.1007/s00520-012-1580-y