Incidence of Hematologic Toxicity in Older Adults Treated with Gemcitabine or a Gemcitabine-Containing Regimen in Routine Clinical Practice: A Multicenter Retrospective Cohort Study

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• 作者：Marie-Rose B. S. Crombag ; Aurelia H. M. de Vries Schultink…
• 刊名：Drugs & Aging
• 出版年：2014
• 出版时间：October 2014
• 年：2014
• 卷：31
• 期：10
• 页码：737-747
• 全文大小：755 KB
• 参考文献：1. Clegg A, Young J, Iliffe S, et al. Frailty in elderly people. Lancet. 2013;381(752-76):2.
  2. Kusagaya H, Inui N, Karayama M, et al. Biweekly combination therapy with gemcitabine and carboplatin compared with gemcitabine monotherapy in elderly patients with advanced non-small-cell lung cancer: a randomized, phase-II study. Lung Cancer. 2012;77:550-. <a class="external" href="http://dx.doi.org/10.1016/j.lungcan.2012.05.106" target="_blank" title="It opens in new window">CrossRefa>
  3. Lewis JH, Kilgore ML, Goldman DP, et al. Participation of patients 65 years of age or older in cancer clinical trials. J Clin Oncol. 2003;21:1383-. <a class="external" href="http://dx.doi.org/10.1200/JCO.2003.08.010" target="_blank" title="It opens in new window">CrossRefa>
  4. Repetto L. Great risk of chemotherapy toxicity in elderly patients with cancer. J Support Oncol. 2003;1:18-4.
  5. Hurria A, Togawa K, Mohile SG, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011;29:3457-5. <a class="external" href="http://dx.doi.org/10.1200/JCO.2011.34.7625" target="_blank" title="It opens in new window">CrossRefa>
  6. Murthy VH, Krumholz HM, Gross CP. Participation in cancer clinical trials: race-, sex-, and age-based disparities. JAMA. 2004;291(22):2720-. <a class="external" href="http://dx.doi.org/10.1001/jama.291.22.2720" target="_blank" title="It opens in new window">CrossRefa>
  7. Villella J, Chalas E. Optimising treatment of elderly patients with ovarian cancer: improving their enrollment in clinical trials. Drugs Aging. 2005;22(2):95-00. <a class="external" href="http://dx.doi.org/10.2165/00002512-200522020-00001" target="_blank" title="It opens in new window">CrossRefa>
  8. US Food and Drug Administration. Official label Gemzar (gemcitabine), NDA 020509 2011. Available at: <a href="http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020509s069lbl.pdf" class="a-plus-plus">http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020509s069lbl.pdfa>.
  9. US Food and Drugs Administration. Official label Paraplatin (carboplatin), NDA 020542 2004. Available at: <a href="http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/20452scs001_paraplatin.lbl.pdf" class="a-plus-plus">http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/20452scs001_paraplatin.lbl.pdfa>.
  10. US Food and Drugs Administration. Official label Platinol (cisplatin), NDA 018057 2011. Available at: <a href="http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018057s081lbl.pdf" class="a-plus-plus">http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018057s081lbl.pdfa>.
  11. Ferrucci L, Guralnik JM, Cavazzini C, et al. The frailty syndrome: a critical issue in geriatric oncology. Crit Rev Oncol Hematol. 2003;46:127-7. <a class="external" href="http://dx.doi.org/10.1016/S1040-8428(02)00177-4" target="_blank" title="It opens in new window">CrossRefa>
  12. Hurria A, Lichtman SM. Pharmacokinetics of chemotherapy in the older patient. Cancer Control. 2007;14:32-3.
  13. Repetto L, Venturino A, Fratino L, et al. Geriatric oncology: a clinical approach to the older patient with cancer. Eur J Cancer. 2003;39:870-0. <a class="external" href="http://dx.doi.org/10.1016/S0959-8049(03)00062-5" target="_blank" title="It opens in new window">CrossRefa>
  14. Seufferlein T, Bachet JB, Van Cutsem E, Rougier P, ESMO Guidelines Working Group. Pancreatic adenocarcinoma: ESMO-ESDO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(Suppl 7):vii33-0. <a class="external" href="http://dx.doi.org/10.1093/annonc/mds224" target="_blank" title="It opens in new window">CrossRefa>
  15. Tempero MA, Arnoletti JP, Behrman SW, Ben-Josef E, Benson AB 3rd, Casper ES, et al. Pancreatic adenocarcinoma, version 2.2012: featured updates to the NCCN Guidelines. J Natl Compr Canc Netw. 2012;10(6):703-3.
  16. Goffin J, Coakley N, Lacchetti C, et al. First-line systemic chemotherapy in the treatment of advanced non-small cell lung cancer. Toronto: Cancer Care Ontario, 2010. (Evidence based series report).
  17. Azzoli CG, Temin S, Aliff T, Baker S Jr, Brahmer J, Johnson DH, et al. 2011 focused update of 2009 American Society of Clinical Oncology clinical practice guideline update on chemotherapy for stage IV non-small-cell lung cancer. J Clin Oncol. 2011;29(28):3825-1. <a class="external" href="http://dx.doi.org/10.1200/JCO.2010.34.2774" target="_blank" title="It opens in new window">CrossRefa>
  18. Peters S, Adjei AA, Gridelli C, Reck M, Kerr K, Felip E, et al. Metastatic non-small-cell lung cancer (NSCLC): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(Suppl 7):vii56-4. <a class="external" href="http://dx.doi.org/10.1093/annonc/mds226" target="_blank" title="It opens in new window">CrossRefa>
  19. de Marinis F, Rossi A, Di Maio M, Ricciardi S, Gridelli C, Italian Association of Thoracic Oncology. Treatment of advanced non-small-cell lung cancer: Italian Association of Thoracic Oncology (AIOT) clinical practice guidelines. Lung Cancer. 2011;73(1):1-0. <a class="external" href="http://dx.doi.org/10.1016/j.lungcan.2011.02.022" target="_blank" title="It opens in new window">CrossRefa>
  20. Babjuk M, Oosterlinck W, Sylvester R, Kaasinen E, Bohle A, Palou-Redorta J, et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder. Eur Urol. 2008;54(2):303-4. <a class="external" href="http://dx.doi.org/10.1016/j.eururo.2008.04.051" target="_blank" title="It opens in new window">CrossRefa>
  21. Jones GRD, Lim E. The national kidney foundation guideline on estimation of the glomerular filtration rate. Clin Biochem Rev. 2003;25:95-.
  22. Hryniuk WM, Goodyear M. The calculation of received dose intensity. J Clin Oncol. 1990;8:1935-.
  23. Park JH, Lee SW, Kim HS, Kang SG, Ko YH, Kim ST, et al. Combination of gemcitabine and carboplatin as first line treatment in elderly patients or those unfit for cisplatin-based chemotherapy with advanced transitional cell carcinoma of the urinary tract. Cancer Chemother Pharmacol. 2013;71(4):1033-. <a class="external" href="http://dx.doi.org/10.1007/s00280-013-2098-9" target="_blank" title="It opens in new window">CrossRefa>
  24. Kurata T, Hirashima T, Iwamoto Y, Kawaguchi T, Ikeda N, Tsuboi M, et al. A phase I/II study of carboplatin plus gemcitabine for elderly patients with advanced non-small cell lung cancer: West Japan Thoracic Oncology Group Trial (WJTOG) 2905. Lung Cancer. 2012;77(1):110-. <a class="external" href="http://dx.doi.org/10.1016/j.lungcan.2011.12.016" target="_blank" title="It opens in new window">CrossRefa>
  25. Genestreti G, Giovannini N, Frizziero M, Maglie M, Sanna S, Cingarlini S, et al. Carboplatin and gemcitabine in first-line treatment of elderly patients with advanced non-small cell lung cancer: data from a retrospective study. J Chemother. 2011;23(4):232-. <a class="external" href="http://dx.doi.org/10.1179/joc.2011.23.4.232" target="_blank" title="It opens in new window">CrossRefa>
  26. Kuriyama H, Kawana K, Taniguchi R, Jono F, Sakai E, Ohubo H, et al. Single-agent gemcitabine in elderly patients with unresectable biliary tract cancer. Hepatogastroenterology. 2011;58(106):270-.
  27. Tibaldi C, Camerini A, D’Incecco A, Vasile E, Fabbri A, Amoroso D, et al. First-line chemotherapy with planned sequential administration of cisplatin/gemcitabine followed by docetaxel in elderly ‘unfrail-patients with advanced non-small-cell lung cancer: a multicenter phase II study. J Cancer Res Clin Oncol. 2012;138(12):2003-. <a class="external" href="http://dx.doi.org/10.1007/s00432-012-1280-5" target="_blank" title="It opens in new window">CrossRefa>
  28. Quoix E. Optimal pharmacotherapeutic strategies for elderly patients with advanced non-small cell lung cancer. Drugs Aging. 2011;28(11):885-4. <a class="external" href="http://dx.doi.org/10.2165/11595100-000000000-00000" target="_blank" title="It opens in new window">CrossRefa>
  29. Inal A, Kaplan MA, Kucukoner M, Urakci Z, Karakus A, Isikdogan A. Cisplatin-based therapy for the treatment of elderly patients with non-small-cell lung cancer: a retrospective analysis of a single institution. Asian Pac J Cancer Prev. 2012;13(5):1837-0. <a class="external" href="http://dx.doi.org/10.7314/APJCP.2012.13.5.1837" target="_blank" title="It opens in new window">CrossRefa>
  30. Joerger M, Burgers JA, Baas P, Doodeman VD, Smits PH, Jansen RS, et al. Gene polymorphisms, pharmacokinetics, and hematological toxicity in advanced non-small-cell lung cancer patients receiving cisplatin/gemcitabine. Cancer Chemother Pharmacol. 2012;69(1):25-3. <a class="external" href="http://dx.doi.org/10.1007/s00280-011-1670-4" target="_blank" title="It opens in new window">CrossRefa>
  31. US Food and Drugs Administration. Official Label Halcion (triazolam), NDA 017892, 2008. Available at: <a href="http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/017892s038lbl.pdf" class="a-plus-plus">http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/017892s038lbl.pdfa>.
  32. Greenblatt DJ, Harmatz JS, Shapiro L, Engelhardt N, Gouthro TA, Shader RI. Sensitivity to triazolam in the elderly. N Engl J Med. 1991;324(24):1691-. <a class="external" href="http://dx.doi.org/10.1056/NEJM199106133242403" target="_blank" title="It opens in new window">CrossRefa>
  33. US Food and Drugs Administration. Official Label Subutex (buprenorphine), NDA 0202732, 2011. Available at: <a href="http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020732s006s007lbl.pdf" class="a-plus-plus">http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020732s006s007lbl.pdfa>.
  34. US Food and Drugs Administration. Official Label Pravachol (pravastatin), NDA 019898, 2001. Available at: <a href="http://www.accessdata.fda.gov/drugsatfda_docs/label/2001/19898s46lbl.pdf" class="a-plus-plus">http://www.accessdata.fda.gov/drugsatfda_docs/label/2001/19898s46lbl.pdfa>.
  35. von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008;61(4):344-. <a class="external" href="http://dx.doi.org/10.1016/j.jclinepi.2007.11.008" target="_blank" title="It opens in new window">CrossRefa>
  36. Gridelli C, Rossi A, Di Maio M, Leo S, Filipazzi V, Favaretto AG. Rationale and design of MILES-3 and MILES-4 studies: two randomized phase 3 trials comparing single-agent chemotherapy versus cisplatin-based doublets in elderly patients with advanced non-small-cell lung cancer. Clin Lung Cancer. 2014;15(2):166-0. <a class="external" href="http://dx.doi.org/10.1016/j.cllc.2013.11.011" target="_blank" title="It opens in new window">CrossRefa>
  37. Pallis AG, Gridelli C. Is age a negative prognostic factor for the treatment of advanced/metastatic non-small-cell lung cancer? Cancer Treat Rev. 2010;36:436-1. <a class="external" href="http://dx.doi.org/10.1016/j.ctrv.2009.12.013" target="_blank" title="It opens in new window">CrossRefa>
  38. Balducci L, Extermann M. Management of cancer in the older person: a practical approach. Oncologist. 2000;5:224-7. <a class="external" href="http://dx.doi.org/10.1634/theoncologist.5-3-224" target="_blank" title="It opens in new window">CrossRefa>
  
• 作者单位：Marie-Rose B. S. Crombag (1) (2)
  Aurelia H. M. de Vries Schultink (3)
  Jan H. M. Schellens (2) (3) (4)
  Jos H. Beijnen (1) (2) (3)
  Alwin D. R. Huitema (1) (2)
  
  1. Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1006 BK, Amsterdam, The Netherlands
  2. Department of Clinical Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
  3. Division of Pharmacoepidemiology and Clinical Pharmacology, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
  4. Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
  
• ISSN：1179-1969

文摘

Purpose Older adults receiving cytotoxic agents may be more susceptible to hematologic toxicities because of progressive reduction in organ functions and multiple co-morbidities. Because older adults are under-represented in clinical trials, this retrospective study aims to evaluate hematologic toxicity of gemcitabine-based regimens in older patients compared with their younger counterparts in clinical practice. Patients and Methods A total of 494 patients routinely treated with gemcitabine, either alone or in combination with platinum-based drugs, in the Slotervaart Hospital or The Netherlands Cancer Institute between January 2003 and January 2013 were enrolled. Patient characteristics, underlying malignancy, treatment regimen, administered doses of gemcitabine, and laboratory values were retrospectively collected from electronic patient records. The relative dose intensity achieved in older patients and their younger counterparts was evaluated using the Wilcoxon rank sum test. Incidence of hematologic toxicity in older adults (age ?0?years) and their younger counterparts (age Results Patient characteristics and baseline laboratory values were equally distributed among the two age groups, except for the estimated glomerular filtration rate being significantly lower in the older patients. Reduction of the first administered dose of gemcitabine was significantly more frequently applied in the older patients (p?=?0.03). However, no significant difference in the gemcitabine relative dose intensity over the median number of four treatment cycles was observed (65?% in the older patients group vs. 67?% in the younger control group). Incidence of severe hematologic toxicity (Grade ?) was not significantly higher in the older patients. A subset analysis of nadir blood counts showed a trend towards an increased incidence of Grade ? hematologic toxicity for the older patients in the gemcitabine-cisplatin treatment group. Moreover, the relative risk for developing Grade 3 or 4 leukocytopenia in the older patients was increased fivefold (p?=?0.007) for combination therapy with gemcitabine and cisplatin. Blood transfusions were administered nearly twofold more frequently in the older patients, but this difference did not reach statistical significance. Conclusion Treatment with gemcitabine or a gemcitabine-containing regimen appeared to be feasible and well tolerated in the older patients who were selected to receive chemotherapy. Overall, patients ?0?years of age did not incur a higher incidence of severe or life-threatening hematologic toxicity nor did they undergo more frequent or larger dose adjustments. These data support additional treatment-specific prospective studies and clinical trials in older cancer patients to optimize treatment benefit and risk in this heterogeneous older patient population.