Seminars in Oncology
Volume 31, Issue 2 , Pages 160-174 , April 2004

Chemotherapy in the elderly

  • Stuart M Lichtman

      Affiliations

    • Don Monti Division of Oncology, North Shore University Hospital, Manhasset, NY, USA
    • Corresponding Author InformationAddress reprint requests to Stuart M. Lichtman, MD, FACP, Director, Geriatric Oncology, Don Monti Division of Medical Oncology, North Shore University Hospital, 300 Community Dr, Manhasset, NY 11030 USA

References 

  1. Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990–2020 (Global Burden of Disease Study). Lancet. 1997;349:1498–1504
  2. Franceschi S, La Vecchia C. Cancer epidemiology in the elderly. Crit Rev Oncol Hematol. 2001;39:219–226
  3. Balducci L, Extermann M. Cancer and aging. An evolving panorama. Hematol Oncol Clin North Am. 2000;14:1–16
  4. Yancik R, Ries LA. Aging and cancer in America. Demographic and epidemiologic perspectives. Hematol Oncol Clin North Am. 2000;14:17–23
  5. Hamerman D. Toward an understanding of frailty. Ann Intern Med. 1999;130:945–950
  6. Morris LA, Grossman R, Barkdoll G, et al.  Information search activities among elderly prescription drug users. J Health Care Mark. 1987;7:5–15
  7. Schmucker DL. Drug disposition in the elderly (a review of the critical factors). J Am Geriatr Soc. 1984;32:144–149
  8. Yuen GJ. Altered pharmacokinetics in the elderly. Clin Geriatr Med. 1990;6:257–267
  9. Baker SD, Grochow LB. Pharmacology of cancer chemotherapy in the older person. Clin Geriatr Med. 1997;13:169–183
  10. Kastrissios H, Blaschke TF. Medication compliance as a feature in drug development. Annu Rev Pharmacol Toxicol. 1997;37:451–475
  11. Egorin MJ. Cancer pharmacology in the elderly. Semin Oncol. 1993;20:43–49
  12. Rossman I. Clinical Geriatrics. (ed 2).. Philadelphia, PA: Lippincott; 1979;
  13. Eisenhauer EA, Vermorken JB, van Glabbeke M. Predictors of response to subsequent chemotherapy in platinum pretreated ovarian cancer (A multivariate analysis of 704 patients). Ann Oncol. 1997;8:963–968
  14. Teicher BA, Ara G, Herbst R, et al.  PEG-hemoglobin (effects on tumor oxygenation and response to chemotherapy). In Vivo. 1997;11:301–311
  15. Schrijvers D, Highley M, De Bruyn E, et al.  Role of red blood cells in pharmacokinetics of chemotherapeutic agents. Anticancer Drugs. 1999;10:147–153
  16. Rieseman C. Antidepressant drug interactions and the cytochrome P450 system (A critical appraisal). Pharmacotherapy. 1995;15:84S–99S
  17. Michalets EL. Update (Clinically significant cytochrome P-450 drug interactions). Pharmacotherapy. 1998;18:84–112
  18. Evans W, Schentag J, Jusko W. Applied Pharmacokinetics, Principles of Therapeutic Drug Monitoring. (ed 3).. Vancouver, WA: Applied Therapeutics, Inc; 1994;
  19. Flockhart D. Cytochrome P450 drug interaction table. 2002; Available at: http://medicine.iupui.edu/flockhart/. Accessed Sept 18
  20. Sotaniemi EA, Arranto AJ, Pelkonen O, et al.  Age and cytochrome P450-linked drug metabolism in humans (An analysis of 226 subjects with equal histopathologic conditions). Clin Pharmacol Ther. 1997;61:331–339
  21. Vestal RE. Aging and pharmacology. Cancer. 1997;80:1302–1310
  22. Balducci L, Corcoran MB. Antineoplastic chemotherapy of the older cancer patient. Hematol Oncol Clin North Am. 2000;14:193–212
  23. Brenner BM, Meyer GW, Hostetter TH. Dietary protein intake and the progressive nature of kidney disease (The role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease). N Engl J Med. 1982;307:652–659
  24. Tauchi H, Tsuboi K, Okutoni J. Age changes in the human kidney of the different races. Gerontology. 1971;17:87–97
  25. Evers BM, Townsend CMJ, Thompson JC. Organ physiology of aging. Surg Clin North Am. 1994;74:23–39
  26. Gelman RS, Taylor SGT. Cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy in women more than 65 years old with advanced breast cancer (The elimination of age trends in toxicity by using doses based on creatinine clearance). J Clin Oncol. 1984;2:1404–1413
  27. Swedko PJ, Clark HD, Paramsothy K, et al.  Serum creatinine is an inadequate screening test for renal failure in elderly patients. Arch Intern Med. 2003;163:356–360
  28. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31–41
  29. Jelliffe RW. Estimation of creatinine clearance when urine cannot be collected. Lancet. 1971;1:975–976
  30. Smythe M, Hoffman J, Kizy K, et al.  Estimating creatinine clearance in elderly patients with low serum creatinine concentrations. Am J Hosp Pharm. 1994;51:198–204
  31. Marx GM, Steer CB, Galani E, et al.  Evaluation of the Cockroft Gault, Jelliffe and Wright formulae in estimating renal function in elderly patients. Proc Am Soc Clin Oncol. 2002;21:1486a; (abstr)
  32. Burkhardt H, Bojarsky G, Gretz N, et al.  Creatinine clearance, Cockcroft-Gault formula and cystatin C (Estimators of true glomerular filtration rate in the elderly?). Gerontology. 2002;48:140–146
  33. Balducci L, Extermann M. Cancer chemotherapy in the older patient (What the medical oncologist needs to know). Cancer. 1997;80:1317–1322
  34. Skirvin JA, Lichtman SM. Pharmacokinetic considerations of oral chemotherapy in elderly patients with cancer. Drugs Aging. 2002;19:25–42
  35. Calvert AH, Newell DR, Gumbrell LA, et al.  Carboplatin dosage (Prospective evaluation of a simple formula based on renal function). J Clin Oncol. 1989;7:1748–1756
  36. Chatelut E, Canal P, Brunner V, et al.  Prediction of carboplatin clearance from standard morphological and biological patient characteristics. J Natl Cancer Inst. 1995;87:573–580
  37. Kintzel PE, Dorr RT. Anticancer drug renal toxicity and elimination (Dosing guidelines for altered renal function). Cancer Treat Rev. 1995;21:33–64
  38. Charlson ME, Pompei P, Ales KL, et al.  A new method of classifying prognostic comorbidity in longitudinal studies (development and validation). J Chronic Dis. 1987;40:373–383
  39. Satariano WA, Ragland DA. The effect of comorbidity on 3-year survival of women with primary breast cancer. Ann Intern Med. 1994;120:104–110
  40. Yancik R, Wesley MN, Ries LA, et al.  Comorbidity and age as predictors of risk for early mortality of male and female colon carcinoma patients (A population-based study). Cancer. 1998;82:2123–2134
  41. Extermann M, Overcash J, Lyman GH, et al.  Comorbidity and functional status are independent in older cancer patients. J Clin Oncol. 1998;16:1582–1587
  42. Rockwood K, Stadnyk K, MacKnight C, et al.  A brief clinical instrument to classify frailty in elderly people. Lancet. 1999;353:205–206
  43. Reuben DB, Rubenstein LV, Hirsch SH, et al.  Value of functional status as a predictor of mortality (Results of a prospective study). Am J Med. 1992;93:663–669
  44. Repetto L, Vercelli M, Simoni C, et al.  Comorbidity among elderly patients with and without cancer. Proc Am Soc Clin Oncol. 1994;13:1625a; (abstr)
  45. Venook AP, Egorin MJ, Rosner GL, et al.  Phase I and pharmacokinetic trial of gemcitabine in patients with hepatic or renal dysfunction (Cancer and Leukemia Group B 9565). J Clin Oncol. 2000;18:2780–2787
  46. Shepherd FA, Abratt RP, Anderson H, et al.  Gemcitabine in the treatment of elderly patients with advanced non-small cell lung cancer. Semin Oncol. 1997;24(suppl 7):S50–S55
  47. Crivellari D, Bonetti M, Castiglione-Gertsch M, et al.  Burdens and benefits of adjuvant cyclophosphamide, methotrexate, and fluorouracil and tamoxifen for elderly patients with breast cancer (The International Breast Cancer Study Group Trial VII). J Clin Oncol. 2000;18:1412–1422
  48. Iyer L, Ratain MJ. 5-Fluorouracil pharmacokinetics (Causes for variability and strategies for modulation in cancer chemotherapy). Cancer Invest. 1999;17:494–506
  49. Diasio RB. Clinical implications of dihydropyrimidine dehydrogenase inhibition. Oncology (Huntingt). 1999;13:17–21
  50. Diasio RB. The role of dihydropyrimidine dehydrogenase (DPD) modulation in 5-FU pharmacology. Oncology (Huntingt). 1998;12:23–27
  51. Grem JL. 5-Fluoropyrimidines: Cancer Chemotherapy and Biotherapy: Principles and Practice. In:  Chabner BA,  Longo DL editor. ed 2.. Philadelphia, PA: Lippincott-Raven; 1996;p. 149–211
  52. Sloan JA, Goldberg RM, Sargent DJ, et al.  Women experience greater toxicity with fluorouracil-based chemotherapy for colorectal cancer. J Clin Oncol. 2002;20:1491–1498
  53. Macdonald JS. Vive la difference (Sex and fluorouracil toxicity). J Clin Oncol. 2002;20:1439–1441
  54. Stein BN, Petrelli NJ, Douglass HO, et al.  Age and sex are independent predictors of 5-fluorouracil toxicity. Analysis of a large scale phase III trial. Cancer. 1995;75:11–17
  55. Popescu RA, Norman A, Ross PJ, et al.  Adjuvant or palliative chemotherapy for colorectal cancer in patients 70 years or older. J Clin Oncol. 1999;17:2412–2418
  56. Chiara S, Nobile M, Vincenti M, et al.  Advanced colorectal cancer in the elderly (Results of consecutive trials with 5-fluorouracil-based chemotherapy). Cancer Chemother Pharmacol. 1998;42:336–340
  57. Sargent DJ, Goldberg RM, Jacobson SD, et al.  A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med. 2001;345:1091–1097
  58. Adkins JC, Peters DH, Markham A. Fludarabine. An update of its pharmacology and use in the treatment of haematological malignancies. Drugs. 1997;53:1005–1037
  59. Lichtman SM, Etcubanas E, Budman DR, et al.  The pharmacokinetics and pharmacodynamics of fludarabine phosphate in patients with renal impairment (A prospective dose adjustment study). Cancer Invest. 2002;20:904–913
  60. Beran M, Kantarjian H, O’Brien S, et al.  Topotecan, a topoisomerase I inhibitor, is active in the treatment of myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood. 1996;88:2473–2479
  61. Relias V, Skirvin JA. Topoisomerase I inhibitors (1. Topotecan). J Oncol Pharm Pract. 1997;3:173–185
  62. O’Reilly S, Armstrong DK, Grochow LB. Life-threatening myelosuppression in patients with occult renal impairment receiving topotecan. Gynecol Oncol. 1997;67:329–330 (letter)
  63. von Pawel J, Gatzemeier U, Pujol J, et al.  Phase II comparator study of oral versus intravenous topotecan in patients with chemosensitive small-cell lung cancer. J Clin Oncol. 2001;19:1743–1749
  64. Tardi P, Choice E, Masin D, et al.  Liposomal encapsulation of topotecan enhances anticancer efficacy in murine and human xenograft models. Cancer Res. 2000;60:3389–4493
  65. Clarke-Pearson D, Van LL, Iveson T, et al.  Oral topotecan as single-agent second-line chemotherapy in patients with advanced ovarian cancer. J Clin Oncol. 2001;19:3967–3975
  66. Friedman HS, Petros WP, Friedman AH, et al.  Irinotecan therapy in adults with recurrent or progressive malignant glioma. J Clin Oncol. 1999;17:1516–1525
  67. Saltz LB, Douillard J-Y, Pirotta N, et al.  Combined analysis of two phase 3 randomized trials comparing irinotecan (C), fluorouracil (F), leucovorin (L) vs F alone as first-line therapy of previously untreated metastatic colorectal cancer (MCRC). Proc Am Soc Clin Oncol. 2000;19:938a; (abstr)
  68. Saltz LB. Irinotecan in the first-line treatment of colorectal cancer. Oncology (Huntingt). 1998;12:54–58
  69. Rougier P, Van Cutsem E, Bajetta E, et al.  Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer. Lancet. 1998;352:1407–1412 [published erratum appears in Lancet 352:1634, 1998]
  70. Fuchs CS, Moore MR, Harker G, et al.  Phase III comparison of two irinotecan dosing regimens in second-line therapy of metastatic colorectal cancer. J Clin Oncol. 2003;21:807–814
  71. Mick R, Gupta E, Vokes EE, et al.  Limited-sampling models for irinotecan pharmacokinetics-pharmacodynamics (Prediction of biliary index and intestinal toxicity). J Clin Oncol. 1996;14:2012–2019
  72. Skirvin J, Relias V. Topoisomerase inhibitors (2. Irinotecan). J Oncol Pharm Pract. 1998;4:103–116
  73. Rothenberg ML, Cox JV, DeVore RF, et al.  A multicenter, phase II trial of weekly irinotecan (CPT-11) in patients with previously treated colorectal carcinoma. Cancer. 1999;85:786–795
  74. Kehrer DF, Sparreboom A, Verweij J, et al.  Modulation of irinotecan-induced diarrhea by cotreatment with neomycin in cancer patients. Clin Cancer Res. 2001;7:1136–1141
  75. Govindarajan R, Heaton KM, Broadwater R, et al.  Effect of thalidomide on gastrointestinal toxic effects of irinotecan. Lancet. 2000;356:566–567
  76. Lin EH, Morris J, Chau NK, et al.  Celecoxib attenuated capecitabine induced hand-and-foot syndrome (HFS) and diarrhea and improved time to tumor progression in metastatic colorectal cancer (MCRC). Proc Am Soc Clin Oncol. 2002;21:2362; (abstr)
  77. Singal PK, Iliskovic N. Doxorubicin-induced cardiomyopathy. N Engl J Med. 1998;339:900–905
  78. Swain SM, Whaley FS, Gerber MC, et al.  Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer. J Clin Oncol. 1997;15:1318–1332
  79. Doroshow JH. Anthracyclines and anthracenediones. In:  Chabner BA,  Longo DL editor. Cancer Chemotherapy and Biotherapy (Principles and Practice). (ed 2).. Philadelphia, PA: Lippincott-Raven; 1996;p. 409–434
  80. Doroshow JH. Doxorubicin-induced cardiac toxicity. N Engl J Med. 1991;324:843–845
  81. McEvoy GK. AHFS 98 (Drug Information). Bethesda, MD: American Society of Health System Pharmacists; 1998;
  82. Dorr RT, Von Hoff DD:. Cancer Chemotherapy Handbook. (ed 2).. Norwalk, CT: Appleton & Lange; 1994;
  83. Ibrahim NK, Hortobagyi GN, Ewer M, et al.  Doxorubicin-induced congestive heart failure in elderly patients with metastatic breast cancer, with long-term follow-up (The M.D. Anderson experience). Cancer Chemother Pharmacol. 1999;43:471–478
  84. Ibrahim NK, Frye DK, Buzdar AU, et al.  Doxorubicin-based chemotherapy in elderly patients with metastatic breast cancer. Tolerance and outcome. Arch Intern Med. 1996;156:882–888
  85. Ibrahim NK, Buzdar AU, Asmar L, et al.  Doxorubicin-based adjuvant chemotherapy in elderly breast cancer patients (The M.D). Anderson experience, with long-term follow-up. Ann Oncol. 2000;11:1597–1601
  86. Dees EC, O’Reilly S, Goodman SN, et al.  A prospective pharmacologic evaluation of age-related toxicity of adjuvant chemotherapy in women with breast cancer. Cancer Invest. 2000;18:521–529
  87. Platel D, Pouna P, Bonoron-Adele S, et al.  Comparative cardiotoxicity of idarubicin and doxorubicin using the isolated perfused rat heart model. Anticancer Drugs. 1999;10:671–676
  88. Robieux I, Spazzapan S, Fratino L, et al.  Pharmacokinetics and safety of idarubicin containing infusion (CIV) in elderly patients with aggressive lymphoma. Proc Am Soc Clin Oncol. 1998;17:854a; (abstr)
  89. Anderlini P, Benjamin RS, Wong FC, et al.  Idarubicin cardiotoxicity (A retrospective study in acute myeloid leukemia and myelodysplasia). J Clin Oncol. 1995;13:2827–2834
  90. Spielmann M, Tubiana-Hulin M, Namer M, et al.  Sequential or alternating administration of docetaxel (Taxotere) combined with FEC in metastatic breast cancer (A randomised phase II trial). Br J Cancer. 2002;86:692–697
  91. Phase III randomized study of fluorouracil, epirubicin, and cyclophosphamide v fluorouracil, doxorubicin, and cyclophosphamide in advanced breast cancer: An Italian multicentre trial. Italian Multicentre Breast Study with Epirubicin. J Clin Oncol. 1988;6:976–982
  92. Praga C, Trave F, Petroccione A, et al.  Anthracycline-induced cardiotoxicity and its relevance in cancer treatment. In:  Nimmo W,  Tucker G editor. Clinical Measurement in Drug Evaluation. London, UK: Wolfe Publishing; 1991;p. 131–142
  93. Nicolella D, Grimaldi G, Colantuoni G, et al.  Weekly low dose epirubicin in elderly cancer patients. Tumori. 1996;82:369–371
  94. Safra T, Muggia F, Jeffers S, et al.  Pegylated liposomal doxorubicin (doxil) (Reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg/m2). Ann Oncol. 2000;11:1029–1033
  95. Muggia FM. Clinical efficacy and prospects for use of pegylated liposomal doxorubicin in the treatment of ovarian and breast cancers. Drugs. 1997;54(suppl 4):22–29
  96. Thomas X, Archimbaud E. Mitoxantrone in the treatment of acute myelogenous leukemia (a review). Hematol Cell Ther. 1997;39:63–74
  97. Ranson MR, Carmichael J, O’Byrne K, et al.  Treatment of advanced breast cancer with sterically stabilized liposomal doxorubicin (results of a multicenter phase II trial). J Clin Oncol. 1997;15:3185–3191
  98. Lichtman SM, Kolitz J, Budman DR, et al.  Treatment of aggressive non-Hodgkin’s lymphoma in elderly patients with thiotepa, novantrone (mitoxantrone), vincristine, prednisone (TNOP). Am J Clin Oncol. 2001;24:360–362
  99. Wiseman LR, Spencer CM. Mitoxantrone. A review of its pharmacology and clinical efficacy in the management of hormone-resistant advanced prostate cancer. Drugs Aging. 1997;10:473–485
  100. Small EJ. Prostate cancer. Curr Opin Oncol. 1997;9:277–286
  101. Cortes JE, Pazdur R. Docetaxel. J Clin Oncol. 1995;13:2643–2655
  102. Kreis W, Budman DR, Fetten J, et al.  Phase I trial of the combination of daily estramustine phosphate and intermittent docetaxel in patients with metastatic hormone refractory prostate carcinoma. Ann Oncol. 1999;10:33–38
  103. Venook AP, Egorin MJ, Rosner GL, et al.  Phase I and pharmacokinetic trial of paclitaxel in patients with hepatic dysfunction (Cancer and Leukemia Group B 9264). J Clin Oncol. 1998;16:1811–1819
  104. Taylor CW, Wang LM, List AF, et al.  Amifostine protects normal tissues from paclitaxel toxicity while cytotoxicity against tumour cells is maintained. Eur J Cancer. 1997;33:1693–1698
  105. Hainsworth JD, Burris HA, Erland JB, et al.  Phase I trial of docetaxel administered by weekly infusion in patients with advanced refractory cancer. J Clin Oncol. 1998;16:2164–2168
  106. Hainsworth JD, Burris HA, Litchy S, et al.  Weekly docetaxel in the treatment of elderly patients with advanced nonsmall cell lung carcinoma. A Minnie Pearl Cancer Research Network phase II trial. Cancer. 2000;89:328–333
  107. Perez EA, Vogel CL, Irwin DH, et al.  Multicenter phase II trial of weekly paclitaxel in women with metastatic breast cancer. J Clin Oncol. 2001;19:4216–4223
  108. Perez EA, Vogel CL, Irwin DH, et al.  Weekly paclitaxel in women age 65 and above with metastatic breast cancer. Breast Cancer Res Treat. 2002;73:85–88
  109. Lichtman SM, Egorin M, Rosner G, et al.  Clinical pharmacology of paclitaxel in relation to patient age (CALGB 9762). Proc Am Soc Clin Oncol. 2001;19:265a; (abstr)
  110. Akerley W, Glantz M, Choy H, et al.  Phase I trial of weekly paclitaxel in advanced lung cancer. J Clin Oncol. 1998;16:153–158
  111. Vahdat L, Papadopoulos K, Lange D, et al.  Reduction of paclitaxel-induced peripheral neuropathy with glutamine. Clin Cancer Res. 2001;7:1192–1197
  112. Burris H. Optimal use of docetaxel (Taxotere) (Maximizing its potential). Anticancer Drugs. 1996;7(suppl 2):25–28
  113. Bruno R, Hille D, Riva A, et al.  Population pharmacokinetics/pharmacodynamics of docetaxel in phase II studies in patients with cancer. J Clin Oncol. 1998;16:187–196
  114. Reed E, Dabholkar M, Chabner BA. Platinum analogues. In:  Chabner BA,  Longo DL editor. Cancer Chemotherapy and Biotherapy (Principles and Practice). (ed 2).. Philadelphia, PA: Lippincott-Raven; 1996;p. 357–378
  115. Hesketh PJ. Treatment of chemotherapy-induced emesis in the 1990s (Impact of the 5-HT3 receptor antagonists). Support Care Cancer. 1994;2:286–292
  116. Lofters W, Pater J, Zee B, et al.  Phase III double-blind comparison of dolasetron mesylate and ondansetron and an evaluation of the additive role of dexamethasone in the prevention of acute and delayed nausea and vomiting due to moderately emetogenic chemotherapy. J Clin Oncol. 1997;15:2966–2973
  117. Blanchley JD, Hill JB. Renal and electrolyte disturbances associated with Cisplatin. Ann Intern Med. 1981;95:628–632
  118. Daugaard G, Abildgaard U. Cisplatin nephrotoxicity. Cancer Chemother Pharmacol. 1988;25:1–9
  119. Becouarn Y, Nguyen B, Brunet R, et al.  Cancer chemotherapy in the elderly (A series of 51 patients aged >70 years). Cancer Chemother Pharmacol. 1992;29:159–163
  120. Hrushesky WJM, Shimp W, Kennedy BJ. Lack of age-dependent cisplatin nephrotoxicity. Am J Med. 1984;76:579–584
  121. Thyss A, Saudes L, Otto J, et al.  Renal tolerance of cisplatin in patients more than 80 years old. J Clin Oncol. 1994;12:2121–2125
  122. Lichtman SM, Buchholtz M, Marino J, et al.  Use of cisplatin for elderly patients. Age Ageing. 1992;21:202–204
  123. Cubillo A, Cornide M, Lopez JL, et al.  Renal tolerance to cisplatin in patients 70 years and older. Am J Clin Oncol. 2001;24:192–197
  124. Langer CJ, Manola J, Bernardo P, et al.  Cisplatin-based therapy for elderly patients with advanced non-small-cell lung cancer (Implications of Eastern Cooperative Oncology Group 5592, a randomized trial). J Natl Cancer Inst. 2002;94:173–181
  125. Lichtman SM. Physiologic aspects of aging. Implications for the treatment of cancer. Drugs Aging. 1995;7:212–225
  126. Kemp G, Rose P, Lurain J, et al.  Amifostine pretreatment for protection against cyclophosphamide-induced and cisplatin-induced toxicities (Results of a randomized control trial in patients with advanced ovarian cancer). J Clin Oncol. 1996;14:2101–2112
  127. Dooley MJ, Poole SG, Rischin D, et al.  Carboplatin dosing (gender bias and inaccurate estimates of glomerular filtration rate). Eur J Cancer. 2002;38:44–51
  128. Donahue A, McCune JS, Faucette S, et al.  Measured versus estimated glomerular filtration rate in the Calvert equation (Influence on carboplatin dosing). Cancer Chemother Pharmacol. 2001;47:373–379
  129. Calvert AH, Egorin MJ. Carboplatin dosing formulae (gender bias and the use of creatinine- based methodologies). Eur J Cancer. 2002;38:11–16
  130. de Gramont A, Figer A, Seymour M, et al.  Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000;18:2938–2947
  131. Tabah-Fisch I, Maindrault-Goebel F, Benavides M, et al.  Oxaliplatin/5FU/LV is feasible, safe and active in elderly colorectal cancer (CRC) patients. Proc Am Soc Clin Oncol. 2002;21:556a; (abstr)
  132. Miller AA, Rosner GL, Ratain MJ, et al.  Pharmacology of 21-day oral etoposide given in combination with i.v. cisplatin in patients with extensive-stage small cell lung cancer (A Cancer and Leukemia Group B study (CALGB 9062)). Clin Cancer Res. 1997;3:719–725
  133. de Jong RS, Hofstra LS, Willemse PH, et al.  Effect of low-dose oral etoposide on serum CA-125 in patients with advanced epithelial ovarian cancer. Gynecol Oncol. 1997;66:197–201
  134. Fleming GF, Waggoner SE, Rotmensch J, et al.  Phase II study of 96-hr continuous-infusion etoposide and doxorubicin with bolus cyclophosphamide in refractory epithelial ovarian cancer. Gynecol Oncol. 1997;65:42–45
  135. Niitsu N, Umeda M. Evaluation of long-term daily administration of oral low-dose etoposide in elderly patients with relapsing or refractory non-Hodgkin’s lymphoma. Am J Clin Oncol. 1997;20:311–314
  136. Gridelli C, Rossi A, Scognamiglio F, et al.  Carboplatin plus oral etoposide in elderly patients with advanced non small cell lung cancer. A phase II study. Anticancer Res. 1997;17:4755–4758
  137. Souhami RL, Spiro SG, Rudd RM, et al.  Five-day oral etoposide treatment for advanced small-cell lung cancer (Randomized comparison with intravenous chemotherapy). J Natl Cancer Inst. 1997;89:577–580
  138. McEvoy G:. AHFS 2000. Drug Information. Bethesda, MD: American Society of Health System Pharmacists; 2000;
  139. Aita P, Robieux I, Sorio R, et al.  Pharmacokinetics of oral etoposide in patients with hepatocellular carcinoma. Cancer Chemother Pharmacol. 1999;43:287–294
  140. LeChevalier T, Brisgand D, Douilland J-Y, et al.  Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer (Results of a European multicenter trial including 612 patients). J Clin Oncol. 1994;12:360–367
  141. Burger RA, DiSaia PJ, Roberts JA, et al.  Phase II trial of vinorelbine in recurrent and progressive epithelial ovarian cancer. E Gynecol Oncol. 1999;72:148–153
  142. Budman DR. Vinorelbine (Navelbine) (A third-generation vinca alkaloid). Cancer Invest. 1997;15:475–490
  143. Frasci G, Lorusso V, Panza N, et al.  Gemcitabine plus vinorelbine versus vinorelbine alone in elderly patients with advanced non-small-cell lung cancer. J Clin Oncol. 2000;18:2529–2536
  144. Sorio R, Robieux I, Galligioni E, et al.  Pharmacokinetics and tolerance of vinorelbine in elderly patients with metastatic breast cancer. Eur J Cancer. 1997;33:301–303
  145. Gauvin A, Pinguet F, Culine S, et al.  Bayesian estimate of vinorelbine pharmacokinetic parameters in elderly patients with advanced metastatic cancer. Clin Cancer Res. 2000;6:2690–2695
  146. Greco FA. Evolving role of oral chemotherapy for the treatment of patients with neoplasms. Oncology. 1998;12:43–50
  147. Liu G, Franssen E, Fitch MI, et al.  Patient preferences for oral versus intravenous palliative chemotherapy. J Clin Oncol. 1997;15:110–115
  148. DeMario MD, Ratain MJ. Oral chemotherapy (rationale and future directions). J Clin Oncol. 1998;16:2557–2567
  149. Bonadonna G, Valagussa P. Dose-response effect of adjuvant chemotherapy in breast cancer. N Engl J Med. 1981;304:101–105
  150. Lebovits AH, Strain JJ, Schleifer SJ, et al.  Patient noncompliance with self-administered chemotherapy. Cancer. 1990;65:17–22
  151. Partridge AH, Avorn J, Wang PS, et al.  Adherence to therapy with oral antineoplastic agents. J Natl Cancer Inst. 2002;94:652–661
  152. Cramer JA. Enhancing patient compliance in the elderly. Role of packaging aids and monitoring. Drugs Aging. 1998;12:7–15
  153. Corcoran ME. Polypharmacy in the older patient with cancer. Cancer Control. 1997;4:419–428
  154. Kivisto KT, Kroemer HK, Eichelbaum M. The role of human cytochrome P450 enzymes in the metabolism of anticancer agents (Implications for drug interactions). Br J Clin Pharmacol. 1995;40:523–530
  155. King RS. Drug interactions with cancer chemotherapy. Cancer Pract. 1995;3:57–59
  156. Cloutier AO. Advanced breast cancer (recent developments in hormonal therapy). Semin Oncol Nurs. 2000;16:206–213
  157. Crucitta E, Lorusso V, Attolico M, et al.  New aromatase inhibitors in the treatment of advanced breast cancer. Int J Oncol. 2000;17:1037–1041
  158. Van Cutsem E, Findlay M, Osterwalder B, et al.  Capecitabine, an oral fluoropyrimidine carbamate with substantial activity in advanced colorectal cancer (Results of a randomized phase II study). J Clin Oncol. 2000;18:1337–1345
  159. O’Shaughnessy J, Moiseyenko V, Bell DV, et al.  A randomized phase II study of Xeloda (capecitabine) vs CMF as first line chemotherapy of breast cancer in women aged 55 years. Proc Am Soc Clin Oncol. 1998;17:398a
  160. Cassidy J, Twelves C, Cameron D, et al.  Bioequivalence of two tablet formulations of capecitabine and exploration of age, gender, body surface area, and creatinine clearance as factors influencing systemic exposure in cancer patients. Cancer Chemother Pharmacol. 1999;44:453–460
  161. Twelves C, Glynne-Jones R, Cassidy J, et al.  Effect of hepatic dysfunction due to liver metastases on the pharmacokinetics of capecitabine and its metabolites. Clin Cancer Res. 1999;5:1696–1702
  162. O’Shaughnessy JA. Potential of capecitabine as first-line therapy for metastatic breast cancer (Dosing recommendations in patients with diminished renal function). Ann Oncol. 2002;13:983; (letter)
  163. Reigner B, Verweij J, Dirix L, et al.  Effect of food on the pharmacokinetics of capecitabine and its metabolites following oral administration in cancer patients. Clin Cancer Res. 1998;4:941–948
  164. Middleton MR, Grob JJ, Aaronson N, et al.  Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol. 2000;18:158–166
  165. Newlands ES, O’Reilly SM, Glaser MG, et al.  The Charing Cross Hospital experience with temozolomide in patients with gliomas. Eur J Cancer. 1996;32A:2236–2241
  166. O’Reilly SM, Newlands ES, Glaser MG, et al.  Temozolomide (a new oral cytotoxic chemotherapeutic agent with promising activity against primary brain tumours). Eur J Cancer. 1993;29A:940–942
  167. Yung WK, Prados MD, Yaya-Tur R, et al.  Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group. J Clin Oncol. 1999;17:2762–2771
  168. Jen JF, Cutler DL, Pai SM, et al.  Population pharmacokinetics of temozolomide in cancer patients. Pharm Res. 2000;17:1284–1289
  169. Brada M, Judson I, Beale P, et al.  Phase I dose-escalation and pharmacokinetic study of temozolomide (SCH 52365) for refractory or relapsing malignancies. Br J Cancer. 1999;81:1022–1030
  170. D’Amato RJ, Loughnan MS, Flynn E, et al.  Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci U S A. 1994;91:4082–4085
  171. Burton E, Prados M. New chemotherapy options for the treatment of malignant gliomas. Curr Opin Oncol. 1999;11:157–161
  172. Singhal S, Mehta J, Desikan R, et al.  Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med. 1999;341:1565–1571
  173. Fine HA, Figg WD, Jaeckle K, et al.  Phase II trial of the antiangiogenic agent thalidomide in patients with recurrent high-grade gliomas. J Clin Oncol. 2000;18:708–715
  174. Chabner BA, Longo DL:. Cancer Chemotherapy and Biotherapy. Principles and Practice. Philadelphia, PA: Lippincott-Raven; 1996;
  175. Rodriguez GI, Kuhn JG, Weiss GR, et al.  A bioavailability and pharmacokinetic study of oral and intravenous hydroxyurea. Blood. 1998;91:1533–1541
  176. Tew KD, Colvin M, Chabner BA. Alkylating agents. In:  Chabner BA,  Longo DL editor. Cancer Chemotherapy and Biotherapy (Principles and Practice). (ed 2).. Philadelphia, PA: Lippincott-Raven; 1996;p. 297–332
  177. Trimble EL, Carter CL, Cain D, et al.  Representation of older patients in cancer treatment trials. Cancer. 1994;74:2208–2214
  178. Lichtman SM. Integration of geriatrics in oncology training-The relationship between the academic center and the community. Crit Rev Oncol Hematol. 2000;33:57–59

PII: S0093-7754(03)00665-1

doi: 10.1053/j.seminoncol.2003.12.027

Seminars in Oncology
Volume 31, Issue 2 , Pages 160-174 , April 2004

Article Tools