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Pharmacological Factors Influencing Anticancer Drug Selection in the Elderly

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Abstract

Persons over the age of 65 years are the fastest growing segment of the US population. In the next 30 years this segment will represent more than 20% of the population. Fifty percent of all cancers occur in this age group and therefore the total cancer burden is expected to rise. Data are becoming available that will better guide the use of chemotherapy in the older patient population. Studies are presented discussing pharmacokinetic data on a number of chemotherapeutic agents with an emphasis on those that have entered clinical practice over the past few years. Many of these agents seem to have a beneficial therapeutic index, particularly in regard to older patients.

Aging can affect the pharmacokinetics of chemotherapy in a number of ways. Absorption is only modified minimally by age. The greater concern with the use of oral drugs is patient compliance. Volume of distribution is affected by changes in body composition, anaemia and decreased plasma albumin concentration. There are many drugs in which renal excretion plays an important role. Decline in glomerular filtration is a consistent phenomenon with aging. Drug metabolism is primarily affected by changes in the P450 system and coadministration of drugs which also interact with this important enzyme system. The selection of chemotherapy in the elderly is frequently determined by degree of comorbidity and the patients’ functional status. These factors are critical and can often determine response and toxicity. This article discusses the changes that occur with antimetabolites, camptothecins, anthracyclines, taxanes, platinum compounds, epipodophyllotoxins and vinca alkaloids.

There has also been an increasing trend toward the use of oral chemotherapy. Factors that must be considered in selecting chemotherapeutic agents include limitations of saturability of absorption, patient compliance and the pharmacokinetic and pharmacodynamic changes that occur in older patients. Interpatient variability and age-related changes in drug metabolism are discussed. Careful attention to the physiological changes with age and dose adjustments necessary for end-organ dysfunction (renal, hepatic) are needed to ensure the safe administration of chemotherapy.

In this article specific diseases are discussed (breast, colon, ovarian and non-small lung cancers) with recommendations for drug selection in adjuvant chemotherapy and the treatment of metastatic disease. Future studies will need to incorporate these various factors to properly evaluate chemotherapy in older patients. Research and educational initiatives targeted to this population will need to be a priority.

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References

  1. Yancik R. Cancer burden in the aged: an epidemiologic and demographic overview. Cancer 1997; 80: 1273–83

    Article  CAS  PubMed  Google Scholar 

  2. Barry P, Katz PR. On cancer screening in the elderly [editorial]. J Am Geriatr Soc 1989; 37: 913–4

    CAS  PubMed  Google Scholar 

  3. Black JS, Kapoor W. Health promotion and disease prevention in older people: our current state of ignorance. J Am Geriatr Soc 1990; 38: 168–72

    CAS  PubMed  Google Scholar 

  4. Robie PW. Cancer screening in the elderly. J Am Geriatr Soc 1989; 37: 888–93

    CAS  PubMed  Google Scholar 

  5. Yancik R, Yates JW. Cancer in the elderly: approaches to diagnosis and treatment. New York (NY): Springer, 1989

    Google Scholar 

  6. Yancik R, Ries LG. Caring for elderly cancer patients: quality assurance considerations. Cancer 1989; 64 (1 Suppl.): 335–41

    Article  CAS  PubMed  Google Scholar 

  7. Hamerman D. Toward an understanding of frailty. Ann Intern Med 1999; 130: 945–50

    CAS  PubMed  Google Scholar 

  8. Morris LA, Grossman R, Barkdoll G, et al. Information search activities among elderly prescription drug users. J Health Care Mark 1987; 7: 5–15

    CAS  PubMed  Google Scholar 

  9. Schmucker DL. Drug disposition in the elderly: a review of the critical factors. J Am Geriatr Soc 1984; 32: 144–9

    CAS  PubMed  Google Scholar 

  10. Yuen GJ. Altered pharmacokinetics in the elderly. Clin Geriatr Med 1990; 6: 257–67

    CAS  PubMed  Google Scholar 

  11. Tumer N, Scarpace PJ, Lowenthal DT. Geriatric pharmacology: basic and clinical considerations. Annu Rev Pharmacol Toxicol 1992; 32: 271–302

    Article  CAS  PubMed  Google Scholar 

  12. Shock NW, Watkin DM, Yiengst BS, et al. Age differences in water content of the body as related to basal oxygen consumption in males. J Gerontol 1963; 18: 1–8

    Article  CAS  PubMed  Google Scholar 

  13. Forbes GB, Reina JC. Adult lean body mass declines with age: some longitudinal observations. Metabolism 1978; 19: 653–63

    Article  Google Scholar 

  14. Adelman LS, Liebman J. Anatomy of body water and electrolytes. Am J Med 1959; 27: 256–77

    Article  Google Scholar 

  15. Repetto L, Vercelli M, Simoni C, et al. Comorbidity among elderly patients with and without cancer [abstract]. Proc Am Soc Clin Oncol 1994; 13: 1625a

    Google Scholar 

  16. Satariano WA, Ragland DA. The effect of comorbidity on 3-year survival of women with primary breast cancer. Ann Intern Med 1994; 120: 104–10

    CAS  PubMed  Google Scholar 

  17. Baker SD, Grochow LB. Pharmacology of cancer chemotherapy in the older person. Clin Geriatr Med 1997; 13: 169–83

    CAS  PubMed  Google Scholar 

  18. Kastrissios H, Blaschke TF. Medication compliance as a feature in drug development. Annu Rev Pharmacol Toxicol 1997; 37: 451–75

    Article  CAS  PubMed  Google Scholar 

  19. Egorin MJ. Cancer pharmacology in the elderly. Semin Oncol 1993; 20: 43–9

    CAS  PubMed  Google Scholar 

  20. Rossman I. Clinical geriatrics. 2nd ed. Philadelphia (PA): Lippincott, 1979

    Google Scholar 

  21. 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: 963–8

    Article  CAS  PubMed  Google Scholar 

  22. Teicher BA, Ara G, Herbst R, et al. Peg-hemoglobin: effects on tumor oxygenation and response to chemotherapy. In Vivo 1997; 11: 301–11

    CAS  PubMed  Google Scholar 

  23. Schrijvers D, Highley M, De Bruyn E, et al. Role of red blood cells in pharmacokinetics of chemotherapeutic agents. Anticancer Drugs 1999; 10: 147–53

    Article  CAS  PubMed  Google Scholar 

  24. Rieseman C. Antidepressant drug interactions and the cytochrome p450 system: a critical appraisal. Pharmacotherapy 1995; 15 (6 Pt 2): 84S–99S

    Google Scholar 

  25. Michalets EL. Update: clinically significant cytochrome p-450 drug interactions. Pharmacotherapy 1998; 18: 84–112

    CAS  PubMed  Google Scholar 

  26. Evans W, Schentag J, Jusko W. Applied pharmacokinetics, principles of therapeutic drug monitoring. 3rd ed. Vancouver (WA): Applied Therapeutics, 1994

    Google Scholar 

  27. Flockhart D. Cytochrome p450 drug interaction table [online]. Available from URL: http://medicineiupuiedu/flockhart/ [Accessed 2002 Sep 18]

  28. 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: 331–9

    Article  CAS  PubMed  Google Scholar 

  29. Vestal RE. Aging and pharmacology. Cancer 1997; 80: 1302–10

    Article  CAS  PubMed  Google Scholar 

  30. Balducci L, Corcoran MB. Antineoplastic chemotherapy of the older cancer patient. Hematol Oncol Clin North Am 2000; 14: 193–212

    Article  CAS  PubMed  Google Scholar 

  31. 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: 652–9

    Article  CAS  PubMed  Google Scholar 

  32. Tauchi H, Tsuboi K, Okutoni J. Age changes in the human kidney of the different races. Gerontology 1971; 17: 87–97

    Article  CAS  Google Scholar 

  33. Evers BM, Townsend CMJ, Thompson JC. Organ physiology of aging. Surg Clin North Am 1994; 74: 23–39

    CAS  PubMed  Google Scholar 

  34. 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: 1404–13

    CAS  PubMed  Google Scholar 

  35. 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

    CAS  PubMed  Google Scholar 

  36. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31–41

    Article  CAS  PubMed  Google Scholar 

  37. Jelliffe RW. Estimation of creatinine clearance when urine cannot be collected. Lancet 1971; I: 975–6

    Article  Google Scholar 

  38. Marx GM, Steer CB, Galani E, et al. Evaluation of the Cockroft Gault, Jelliffe and Wright formulae in estimating renal function in elderly patients [abstract]. Proc Annu Meet Am Soc Clin Oncol 2002; 21: 1486a

    Google Scholar 

  39. Balducci L, Extermann M. Cancer chemotherapy in the older patient: what the medical oncologist needs to know. Cancer 1997; 80: 1317–22

    Article  CAS  PubMed  Google Scholar 

  40. Skirvin JA, Lichtman SM. Pharmacokinetic considerations of oral chemotherapy in elderly patients with cancer. Drugs Aging 2002; 19: 25–42

    Article  CAS  PubMed  Google Scholar 

  41. Kintzel PE, Dorr RT. Anticancer drug renal toxicity and elimination: dosing guidelines for altered renal function. Cancer Treat Rev 1995; 21: 33–64

    Article  CAS  PubMed  Google Scholar 

  42. Calvert AH, Newell DR, Gumbrell LA, et al. Carboplatin dosage: prospective evaluation of a simple formula based. J Clin Oncol 1989; 7: 1748–56

    CAS  PubMed  Google Scholar 

  43. 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: 573–80

    Article  CAS  PubMed  Google Scholar 

  44. Borkowski JM, Duerr M, Donehower RC, et al. Relation between age and clearance rate of nine investigational anticancer drugs from phase I pharmacokinetic data. Cancer Chemother Pharmacol 1994; 33: 493–6

    Article  CAS  PubMed  Google Scholar 

  45. 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: 373–83

    Article  CAS  PubMed  Google Scholar 

  46. 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: 2123–34

    Article  CAS  PubMed  Google Scholar 

  47. Extermann M, Overcash J, Lyman GH, et al. Comorbidity and functional status are independent in older cancer patients. J Clin Oncol 1998; 16: 1582–7

    CAS  PubMed  Google Scholar 

  48. Rockwood K, Stadnyk K, MacKnight C, et al. A brief clinical instrument to classify frailty in elderly people. Lancet 1999; 353: 205–6

    Article  CAS  PubMed  Google Scholar 

  49. Reuben DB, Rubenstein LV, Hirsch SH, et al. Value of functional status as a predictor of mortality: results of a prospective study. Am J Med1992; 93: 663–9

    Article  CAS  PubMed  Google Scholar 

  50. Burn PA Jr, Kelly K. New chemotherapeutic agents prolong survival and improve quality of life in non-small cell lung cancer: a review of the literature and future directions. Clin Cancer Res 1998; 4: 1087–100

    Google Scholar 

  51. Stadler WM, Kuzel T, Roth B, et al. Phase II study of singleagent gemcitabine in previously untreated patients with metastatic urothelial cancer. J Clin Oncol 1997; 15: 3394–8

    CAS  PubMed  Google Scholar 

  52. 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 (2 Suppl. 7): S50–5

    Google Scholar 

  53. Bass AJ, Gockerman JP, Hammett E, et al. Phase I evaluation of prolonged-infusion gemcitabine with irinotecan for relapsed or refractory leukemia or lymphoma. J Clin Oncol 2002; 20: 2995–3000

    Article  CAS  PubMed  Google Scholar 

  54. Dumontet C, Morschhauser F, Solal-Celigny P, et al. Gemcitabine as a single agent in the treatment of relapsed or refractory low-grade non-Hodgkin’s lymphoma. Br J Haematol 2001; 113: 772–8

    Article  CAS  PubMed  Google Scholar 

  55. Savage DG, Rule SA, Tighe M, et al. Gemcitabine for relapsed or resistant lymphoma. Ann Oncol 2000; 11: 595–7

    Article  CAS  PubMed  Google Scholar 

  56. 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(14): 2780–7

    CAS  PubMed  Google Scholar 

  57. 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: 1412–22

    CAS  PubMed  Google Scholar 

  58. Iyer L, Ratain MJ. 5-fluorouracil pharmacokinetics: causes for variability and strategies for modulation in cancer chemotherapy. Cancer Invest 1999; 17: 494–506

    Article  CAS  PubMed  Google Scholar 

  59. Diasio RB. Clinical implications of dihydropyrimidine dehydrogenase inhibition. Oncology (Huntingt) 1999; 13: 17–21

    CAS  Google Scholar 

  60. Diasio RB. The role of dihydropyrimidine dehydrogenase (dpd) modulation in 5-FU pharmacology. Oncology (Huntingt) 1998; 12: 23–7

    CAS  Google Scholar 

  61. Grem JL. 5-fluoropyrimidines. In: Chabner BA, Longo DL, editors. Cancer chemotherapy and biotherapy: principles and practice. 2nd ed. Philadelphia (PA): Lippincott-Raven, 1996: 149–211

    Google Scholar 

  62. Sloan JA, Goldberg RM, Sargent DJ, et al. Women experience greater toxicity with fluorouracil-based chemotherapy for colorectal cancer. J Clin Oncol 2002; 20: 1491–8

    Article  CAS  PubMed  Google Scholar 

  63. Macdonald JS. Vive la difference: sex and fluorouracil toxicity. J Clin Oncol 2002; 20: 1439–41

    PubMed  Google Scholar 

  64. 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: 11–7

    Article  CAS  PubMed  Google Scholar 

  65. 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: 2412–8

    CAS  PubMed  Google Scholar 

  66. 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: 336–40

    Article  CAS  PubMed  Google Scholar 

  67. 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: 1091–7

    Article  CAS  PubMed  Google Scholar 

  68. Sargent DJ, Niedzwiecki D, O’Connell MJ, et al. Recommendation for caution with irinotecan, fluorouracil, and leucovorin for colorectal cancer. N Engl J Med 2001; 345: 144–6

    Article  CAS  PubMed  Google Scholar 

  69. Adkins JC, Peters DH, Markham A. Fludarabine: an update of its pharmacology and use in the treatment of haematological malignancies. Drugs 1997; 53: 1005–37

    CAS  PubMed  Google Scholar 

  70. 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: 904–13

    Article  CAS  PubMed  Google Scholar 

  71. 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: 2473–29

    CAS  PubMed  Google Scholar 

  72. Relias V, Skirvin JA. Topoisomerase I inhibitors: 1. Topotecan. J Oncol Pharm Practice 1997; 3: 173–85

    Article  CAS  Google Scholar 

  73. O’Reilly S, Armstrong DK, Grochow LB. Life-threatening myelosuppressionin patients with occult renal impairment receiving topotecan [letter]. Gynecol Oncol 1997; 67: 329–30

    Article  PubMed  Google Scholar 

  74. 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: 1743–9

    Google Scholar 

  75. 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: 3389–93

    CAS  PubMed  Google Scholar 

  76. 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: 3967–75

    CAS  PubMed  Google Scholar 

  77. Friedman HS, Petros WP, Friedman AH, et al. Irinotecan therapy in adults with recurrent or progressive malignant glioma. J Clin Oncol 1999; 17: 1516–25

    CAS  PubMed  Google Scholar 

  78. 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) [abstract]. Proc Annu Meet Am Soc Clin Oncol 2000; 19: 938a

    Google Scholar 

  79. Saltz LB. Irinotecan in the first-line treatment of colorectal cancer. Oncology (Huntingt) 1998; 12: 54–8

    CAS  Google Scholar 

  80. 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 [published erratum appears in Lancet 1998 Nov 14; 352 (9140): 1634]. Lancet 1998; 352: 1407–12

    Article  CAS  PubMed  Google Scholar 

  81. 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: 1136–41

    CAS  PubMed  Google Scholar 

  82. Skirvin J, Relias V. Topoisomerase inhibitors: 2. Irinotecan. J Oncol Pharm Practice 1998; 4: 103–16

    Article  CAS  Google Scholar 

  83. 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: 786–95

    Article  CAS  PubMed  Google Scholar 

  84. Singal PK, Iliskovic N. Doxorubicin-induced cardiomyopathy. N Engl J Med 1998; 339: 900–5

    Article  CAS  PubMed  Google Scholar 

  85. Swain SM, Whaley FS, Gerber MC, et al. Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer. J Clin Oncol 1997; 15: 1318–32

    CAS  PubMed  Google Scholar 

  86. Doroshow JH. Anthracyclines and anthracenediones. In: Chabner BA, Longo DL, editors. Cancer chemotherapy and biotherapy: principles and practice. 2nd ed. Philadelphia (PA): Lippincott-Raven, 1996: 409–34

    Google Scholar 

  87. Doroshow JH. Doxorubicin-induced cardiac toxicity. N Engl J Med 1991; 324: 843–5

    Article  CAS  PubMed  Google Scholar 

  88. McEvoy GK. Ahfs 98: drug information. Bethesda (MD): American Society of Health System Pharmacists, 1998

    Google Scholar 

  89. Dorr RT, Von Hoff DD. Cancer chemotherapy handbook. 2nd ed. Norwalk (CT): Appleton & Lange, 1994

    Google Scholar 

  90. Ibrahim NK, Hortobagyi GN, Ewer M, et al. Doxorubicininduced 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: 471–8

    Article  CAS  PubMed  Google Scholar 

  91. 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: 882–8

    Article  CAS  PubMed  Google Scholar 

  92. 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: 1597–601

    Article  CAS  PubMed  Google Scholar 

  93. 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: 521–9

    Article  CAS  PubMed  Google Scholar 

  94. 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: 671–6

    Article  CAS  PubMed  Google Scholar 

  95. Robieux I, Spazzapan S, Fratino L, et al. Pharmacokinetics and safety of idarubicin containing infusion (civ) in elderly patients with aggressive lymphoma [abstract]. Proc Annu Meet Am Soc Clin Oncol 1998: 854a

    Google Scholar 

  96. Anderlini P, Benjamin RS, Wong FC, et al. Idarubicin cardiotoxicity: a retrospective study in acute myeloid leukemia and myelodysplasia. J Clin Oncol 1995; 13: 2827–34

    CAS  PubMed  Google Scholar 

  97. 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: 692–7

    Article  CAS  PubMed  Google Scholar 

  98. Italian multicentre breast study with epirubicin. Phase III randomized study of fluorouracil, epirubicin, and cyclophosphamide v fluorouracil, doxorubicin, and cyclophosphamide in advanced breast cancer: an Italian multicentre trial. J Clin Oncol 1988; 6: 976–82

    Google Scholar 

  99. Praga C, Trave F, Petroccione A, et al. Anthracycline-induced cardiotoxicity and its relevance in cancer treatment. In: Nimmo W, Tucker G, editors. Clinical measurement in drug evaluation. London: Wolfe Publishing, 1991: 131–42

    Google Scholar 

  100. Nicolella D, Grimaldi G, Colantuoni G, et al. Weekly low dose epirubicin in elderly cancer patients. Tumori 1996; 82: 369–71

    CAS  PubMed  Google Scholar 

  101. 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: 1029–33

    Article  CAS  PubMed  Google Scholar 

  102. Muggia FM. Clinical efficacy and prospects for use of pegylated liposomal doxorubicin in the treatment of ovarian and breast cancers. Drugs 1997; 54Suppl. 4: 22–9

    Article  CAS  PubMed  Google Scholar 

  103. Thomas X, Archimbaud E. Mitoxantrone in the treatment of acute myelogenous leukemia: a review. Hematol Cell Ther 1997; 39: 63–74

    Article  CAS  PubMed  Google Scholar 

  104. 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: 3185–91

    CAS  PubMed  Google Scholar 

  105. 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: 360–2

    Article  CAS  PubMed  Google Scholar 

  106. 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: 473–85

    Article  CAS  PubMed  Google Scholar 

  107. Small EJ. Prostate cancer. Curr Opin Oncol1997; 9: 277–86

    Article  CAS  PubMed  Google Scholar 

  108. Cortes JE, Pazdur R. Docetaxel. J Clin Oncol 1995; 13: 2643–55

    CAS  PubMed  Google Scholar 

  109. 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: 33–8

    Article  CAS  PubMed  Google Scholar 

  110. 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: 1811–9

    CAS  PubMed  Google Scholar 

  111. 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: 1693–8

    Article  CAS  PubMed  Google Scholar 

  112. Hainsworth JD, Burris III 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: 2164–8

    CAS  PubMed  Google Scholar 

  113. Hainsworth JD, Burris III 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: 328–33

    Article  CAS  PubMed  Google Scholar 

  114. 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: 4216–23

    CAS  PubMed  Google Scholar 

  115. 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: 85–8

    Article  CAS  PubMed  Google Scholar 

  116. Lichtman SM, Egorin M, Rosner G, et al. Clinical pharmacology of paclitaxel in relation to patient age: CALGB 9762 [abstract]. Proc Annu Meet Am Soc Clin Oncol 2001; 19: 265a

    Google Scholar 

  117. Akerley W, Glantz M, Choy H, et al. Phase I trial of weekly paclitaxel in advanced lung cancer. J Clin Oncol 1998; 16: 153–8

    CAS  PubMed  Google Scholar 

  118. Vahdat L, Papadopoulos K, Lange D, et al. Reduction of paclitaxel-induced peripheral neuropathy with glutamine. Clin Cancer Res 2001; 7: 1192–7

    CAS  PubMed  Google Scholar 

  119. Burris H. Optimal use of docetaxel (Taxotere):maximizing its potential. Anticancer Drugs 1996; 7Suppl. 2: 25–8

    CAS  PubMed  Google Scholar 

  120. 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: 187–96

    CAS  PubMed  Google Scholar 

  121. Reed E, Dabholkar M, Chabner BA. Platinum analogues. In: Chabner BA, Longo DL, editors. Cancer chemotherapy and biotherapy: principles and practice. 2nd ed. Philadelphia (PA): Lippincott-Raven, 1996: 357–78

    Google Scholar 

  122. Hesketh PJ. Treatment of chemotherapy-induced emesis in the 1990s: impact of the 5-HT3 receptor antagonists. Support Care Cancer 1994; 2: 286–92

    Article  CAS  PubMed  Google Scholar 

  123. 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: 2966–73

    CAS  PubMed  Google Scholar 

  124. Lichtman SM. Physiological aspects of aging: implications for the treatment of cancer. Drugs Aging 1995; 7: 212–25

    Article  CAS  PubMed  Google Scholar 

  125. Blanchley JD, Hill JB. Renal and electrolyte disturbances associated with cisplatin. Ann Intern Med 1981; 95: 628–32

    Google Scholar 

  126. Daugaard G, Abildgaard U. Cisplatin nephrotoxicity. Cancer Chemother Pharmacol 1988; 25: 1–9

    Article  Google Scholar 

  127. 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: 159–63

    Article  Google Scholar 

  128. Hrushesky WJM, Shimp W, Kennedy BJ. Lack of age-dependent cisplatin nephrotoxicity. Am J Med 1984; 76: 579–84

    Article  CAS  PubMed  Google Scholar 

  129. Thyss A, Saudes L, Otto J, et al. Renal tolerance of cisplatin in patients more than 80 years old. J Clin Oncol 1994; 12: 2121–5

    CAS  PubMed  Google Scholar 

  130. Lichtman SM, Buchholtz M, Marino J, et al. Use of cisplatin for elderly patients. Age Ageing 1992; 21: 202–4

    Article  CAS  PubMed  Google Scholar 

  131. Cubillo A, Cornide M, Lopez JL, et al. Renal tolerance to cisplatin in patients 70 years and older. Am J Clin Oncol 2001; 24: 192–7

    Article  CAS  PubMed  Google Scholar 

  132. 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: 2101–12

    CAS  PubMed  Google Scholar 

  133. 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

    Article  CAS  PubMed  Google Scholar 

  134. 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: 373–9

    Article  CAS  PubMed  Google Scholar 

  135. Calvert AH, Egorin MJ. Carboplatin dosing formulae: gender bias and the use of creatinine-based methodologies. Eur J Cancer 2002; 38: 11–6

    Article  CAS  PubMed  Google Scholar 

  136. 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: 2938–47

    PubMed  Google Scholar 

  137. Extra JM, Marty M, Brienza S, et al. Pharmacokinetics and safety profile of oxaliplatin. Semin Oncol 1998; 25: 13–22

    CAS  PubMed  Google Scholar 

  138. Piccart M, Green J, Lacave A, et al. Oxaliplatin or paclitaxel in patients with platinum-pretreated advanced ovarian cancer: a randomized phase II study of the European Organization for Research and Treatment of Cancer gynecology group. J Clin Oncol 2000; 18: 1193–202

    CAS  PubMed  Google Scholar 

  139. 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: 719–25

    CAS  PubMed  Google Scholar 

  140. 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

    Article  PubMed  Google Scholar 

  141. 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: 42–5

    Article  CAS  PubMed  Google Scholar 

  142. 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: 311–4

    Article  CAS  PubMed  Google Scholar 

  143. 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: 4755–8

    CAS  PubMed  Google Scholar 

  144. 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: 577–80

    Article  CAS  PubMed  Google Scholar 

  145. McEvoy G. AHFS 2000: drug information. Bethesda (MD): American Society of Health System Pharmacists, 2000

    Google Scholar 

  146. Aita P, Robieux I, Sorio R, et al. Pharmacokinetics of oral etoposide in patients with hepatocellular carcinoma. Cancer Chemother Pharmacol 1999; 43: 287–94

    Article  CAS  PubMed  Google Scholar 

  147. 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: 360–7

    CAS  Google Scholar 

  148. Burger RA, Burman S, White R, et al. Phase II trial of navelbine in advanced epithelial ovarian cancer [abstract]. Proc Annu Meet Am Soc Clin Oncol 1996; 15

    Google Scholar 

  149. Budman DR. Vinorelbine (navelbine): a third-generation vinca alkaloid. Cancer Invest 1997; 15: 475–90

    Article  CAS  PubMed  Google Scholar 

  150. 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: 2529–36

    CAS  PubMed  Google Scholar 

  151. 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: 301–3

    Article  CAS  PubMed  Google Scholar 

  152. 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: 2690–5

    CAS  PubMed  Google Scholar 

  153. Greco FA. Evolving role of oral chemotherapy for the treatment of patients with neoplasms. Oncology 1998; 12: 43–50

    CAS  PubMed  Google Scholar 

  154. DeMario MD, Ratain MJ. Oral chemotherapy: rationale and future directions. J Clin Oncol 1998; 16: 2557–67

    CAS  PubMed  Google Scholar 

  155. Liu G, Franssen E, Fitch MI, et al. Patient preferences for oral versus intravenous palliative chemotherapy. J Clin Oncol 1997; 15: 110–5

    CAS  PubMed  Google Scholar 

  156. Bonadonna G, Valagussa P. Dose-response effect of adjuvant chemotherapy in breast cancer. N Engl J Med 1981; 304: 101–5

    Article  Google Scholar 

  157. Lebovits AH, Strain JJ, Schleifer SJ, et al. Patient noncompliance with self-administered chemotherapy. Cancer 1990; 65: 17–22

    Article  CAS  PubMed  Google Scholar 

  158. Col N, Fanale JE, Kronholm P. The role of medication noncompliance and adverse drug reactions in hospitalizations of the elderly. Arch Intern Med 1990; 150: 841–5

    Article  CAS  PubMed  Google Scholar 

  159. Cramer JA. Enhancing patient compliance in the elderly: role of packaging aids and monitoring. Drugs Aging 1998; 12: 7–15

    Article  CAS  PubMed  Google Scholar 

  160. Richardson JL, Shelton DR, Krailo M, et al. The effect of compliance with treatment on survival among patients with hematologic malignancies. J Clin Oncol 1990; 8: 356–64

    CAS  PubMed  Google Scholar 

  161. Levine AM, Richardson JL, Marks G, et al. Compliance with oral drug therapy in patients with hematologic malignancy. J Clin Oncol 1987; 5: 1469–76

    CAS  PubMed  Google Scholar 

  162. Richardson JL, Marks G, Levine A. The influence of symptoms of disease and side effects of treatment on compliance with cancer therapy. J Clin Oncol 1988; 6: 1746–52

    CAS  PubMed  Google Scholar 

  163. Lee CR, Nicholson PW, Souhami RL, et al. Patient compliance with prolonged low-dose oral etoposide for small cell lung cancer. Br J Cancer 1993; 67: 630–4

    Article  CAS  PubMed  Google Scholar 

  164. Urquhart J. Patient compliance with crucial drug regimens: implications for prostate cancer. Eur Urol 1996; 29: 124–31

    PubMed  Google Scholar 

  165. Partridge AH, Avorn J, Wang PS, et al. Adherence to therapy with oral antineoplastic agents. J Natl Cancer Inst 2002; 94: 652–61

    Article  PubMed  Google Scholar 

  166. Corcoran ME. Polypharmacy in the older patient with cancer. Cancer Control 1997; 4: 419–28

    PubMed  Google Scholar 

  167. 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: 523–30

    Article  CAS  PubMed  Google Scholar 

  168. King RS. Drug interactions with cancer chemotherapy. Cancer Pract 1995; 3: 57–9

    CAS  PubMed  Google Scholar 

  169. Cloutier AO. Advanced breast cancer: recent developments in hormonal therapy. Semin Oncol Nurs 2000; 16: 206–13

    Article  CAS  PubMed  Google Scholar 

  170. Crucitta E, Lorusso V, Attolico M, et al. New aromatase inhibitors in the treatment of advanced breast cancer [review]. Int J Oncol 2000; 17: 1037–41

    CAS  PubMed  Google Scholar 

  171. 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: 1337–45

    PubMed  Google Scholar 

  172. 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 [abstract]. Proc Annu Meet Am Soc Clin Oncol 1998: 398a

    Google Scholar 

  173. 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: 453–60

    Article  CAS  PubMed  Google Scholar 

  174. 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: 1696–702

    CAS  PubMed  Google Scholar 

  175. O’Shaughnessy JA. Potential of capecitabine as first-line therapy for metastatic breast cancer: dosing recommendations in patients with diminished renal function [letter]. Ann Oncol 2002; 13: 983

    Article  PubMed  Google Scholar 

  176. 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: 941–8

    CAS  PubMed  Google Scholar 

  177. 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: 158–66

    CAS  PubMed  Google Scholar 

  178. 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: 2236–41

    Article  CAS  PubMed  Google Scholar 

  179. 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: 940–2

    Article  PubMed  Google Scholar 

  180. 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: 2762–71

    CAS  PubMed  Google Scholar 

  181. Jen JF, Cutler DL, Pai SM, et al. Population pharmacokinetics of temozolomide in cancer patients. Pharm Res 2000; 17: 1284–9

    Article  CAS  PubMed  Google Scholar 

  182. 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: 1022–30

    Article  CAS  PubMed  Google Scholar 

  183. D’Amato RJ, Loughnan MS, Flynn E, et al. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci U S A 1994; 91: 4082–5

    Article  PubMed  Google Scholar 

  184. Burton E, Prados M. New chemotherapy options for the treatment of malignant gliomas. Curr Opin Oncol 1999; 11: 157–61

    Article  CAS  PubMed  Google Scholar 

  185. Singhal S, Mehta J, Desikan R, et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999; 341: 1565–71

    Article  CAS  PubMed  Google Scholar 

  186. 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: 708–15

    CAS  PubMed  Google Scholar 

  187. Chabner BA, Longo DL. Cancer chemotherapy and biotherapy: principles and practice. Philadelphia (PA): Lippincott-Raven, 1996

    Google Scholar 

  188. Rodriguez GI, Kuhn JG, Weiss GR, et al. A bioavailability and pharmacokinetic study of oral and intravenous hydroxyurea. Blood 1998; 91: 1533–41

    CAS  PubMed  Google Scholar 

  189. Tew KD, Colvin M, Chabner BA. Alkylating agents. In: Chabner BA, Longo DL, editors. Cancer chemotherapy and biotherapy: principles and practice. 2nd ed. Philadelphia (PA): Lippincott-Raven, 1996: 297–332

    Google Scholar 

  190. Jacobson JS, Workman SB, Kronenberg F. Research on complementary and alternative therapies for cancer: issues and methodological considerations. J Am Med Womens Assoc 1999; 54: 177–180, 3

    CAS  PubMed  Google Scholar 

  191. Ernst E, Cassileth BR. The prevalence of complementary/alternative medicine in cancer: a systematic review. Cancer 1998; 83: 777–82

    Article  CAS  PubMed  Google Scholar 

  192. Mathijssen RHJ, Verweij J, de Bruijn P, et al. Effects of St John’s wort on irinotecan metabolism. J Natl Cancer Inst 2002; 94: 1247–9

    Article  CAS  PubMed  Google Scholar 

  193. Mansky PJ, Straus SE. St John’s wort: more implications for cancer patients. J Natl Cancer Inst 2002; 94: 1187–8

    Article  CAS  PubMed  Google Scholar 

  194. Johne A, Brockmoller J, Bauer S, et al. Pharmacokinetic interaction of digoxin with an herbal extract from St John’s wort (Hypericum perforatum). Clin Pharmacol Ther 1999; 66: 338–45

    Article  CAS  PubMed  Google Scholar 

  195. Ernst E. Second thoughts about safety of St John’s wort. Lancet 1999; 354: 2014–6

    Article  CAS  PubMed  Google Scholar 

  196. Piscitelli SC, Burstein AH, Chaitt D, et al. Indinavir concentrations and St John’s wort [letter]. Lancet 2000; 355: 547–8

    Article  CAS  PubMed  Google Scholar 

  197. Ruschitzka F, Meier PJ, Turina M, et al. Acute heart transplant rejection due to Saint John’s wort [letter]. Lancet 2000; 355: 548–9

    Article  CAS  PubMed  Google Scholar 

  198. Dresser GK, Spence JD, Bailey DG. Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome p450 3a4 inhibition. Clin Pharmacokinet 2000; 38: 41–57

    Article  CAS  PubMed  Google Scholar 

  199. Yue QY, Bergquist C, Gerden B. Safety of St John’s wort (Hypericum perforatum) [letter]. Lancet 2000; 355: 576–7

    Article  CAS  PubMed  Google Scholar 

  200. International Breast Cancer Study Group (IBCSG). Endocrine responsiveness and tailoring adjuvant therapy for postmenopausal lymph node-negative breast cancer: a randomized trial. J Natl Cancer Inst 2002; 94: 1054–65

    Article  Google Scholar 

  201. Buzdar AU, Singletary SE, Valero V, et al. Evaluation of paclitaxel in adjuvant chemotherapy for patients with operable breast cancer: preliminary data of a prospective randomized trial. Clin Cancer Res 2002; 8: 1073–9

    CAS  PubMed  Google Scholar 

  202. Thomssen C. Trials of new combinations of herceptin in metastatic breast cancer. Anticancer Drugs 2001; 12Suppl. 4: S19–25

    Article  PubMed  Google Scholar 

  203. Burstein H, Kuter I, Campos S, et al. Clinical activity of trastuzumab and vinorelbine in women with her2-overexpres-sing metastatic breast cancer. J Clin Oncol 2001; 19: 2722–30

    CAS  PubMed  Google Scholar 

  204. Sundararajan V, Mitra N, Jacobson JS, et al. Survival associated with 5-fluorouracil: based adjuvant chemotherapy among elderly patients with node-positive colon cancer. Ann Intern Med 2002; 136: 349–57

    CAS  PubMed  Google Scholar 

  205. Mamounas E, Wieand S, Wolmark N, et al. Comparative efficacy of adjuvant chemotherapy in patients with Dukes’ B versus Dukes’ C colon cancer: results from four national surgical adjuvant breast and bowel project adjuvant studies (c-01, c-02,c-03, and c-04). J Clin Oncol 1999; 17: 1349–55

    CAS  PubMed  Google Scholar 

  206. Schrag D, Cramer LD, Bach PB, et al. Age and adjuvant chemotherapy use after surgery for stage III colon cancer. J Natl Cancer Inst 2001; 93: 850–7

    Article  CAS  PubMed  Google Scholar 

  207. Potosky AL, Harlan LC, Kaplan RS, et al. Age, sex, and racial differences in the use of standard adjuvant therapy for colorectal cancer. J Clin Oncol 2002; 20: 1192–202

    Article  PubMed  Google Scholar 

  208. Pazdur R, Zinner R, Rothernberg ML, et al. Age as a risk factor in irinotecan treatment of 5-FU-refractory colorectal cancer [abstract]. Proc Annu Meet Am Soc Clin Oncol 1997, 921a

    Google Scholar 

  209. Schaaf L, Ichhpurani N, Elfring G, et al. Influence of age on the pharmacokinetics of irinotecan and its metabolites, SN-38 and SN-38 glucuronide, in patients with previously treated colorectal cancer [abstract]. Proc Annu Meet Am Soc Clin Oncol 1997; 16: 202

    Google Scholar 

  210. Camptosar® [prescribing information]. Kalamazoo (MI): Pharmacia & Upjohn Co., 2002

  211. Kehrer DFS, Mathijssen RHJ, Verweij J, et al. Modulation of irinotecan metabolism by ketoconazole. J Clin Oncol 2002; 20: 3122–9

    Article  CAS  PubMed  Google Scholar 

  212. Govindarajan R, Heaton KM, Broadwater R, et al. Effect of thalidomide on gastrointestinal toxic effects of irinotecan. Lancet 2000; 356: 566–7

    Article  CAS  PubMed  Google Scholar 

  213. Saltz LB, Cox JV, Blanke C, et al. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer: Irinotecan Study Group. N Engl J Med 2000; 343: 905–14

    Article  CAS  PubMed  Google Scholar 

  214. Van Cutsem E, Twelves C, Cassidy J, et al. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol 2001; 19: 4097–106

    PubMed  Google Scholar 

  215. Hoff PM, Ansari R, Batist G, et al. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol 2001; 19: 2282–92

    CAS  PubMed  Google Scholar 

  216. Sundararajan V, Hershman D, Grann VR, et al. Variations in the use of chemotherapy for elderly patients with advanced ovarian cancer: a population-based study. J Clin Oncol 2002; 20: 173–8

    Article  PubMed  Google Scholar 

  217. McGuire WP, Hoskins WJ, Brady MF, et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med 1996; 334: 1–6

    Article  CAS  PubMed  Google Scholar 

  218. Neijt JP, Engelholm SA, Tuxen MK, et al. Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carboplatin in advanced ovarian cancer. J Clin Oncol 2000; 18: 3084–92

    CAS  PubMed  Google Scholar 

  219. 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: 173–81

    Article  PubMed  Google Scholar 

  220. Ozols RF. Optimum chemotherapy for ovarian cancer. Int J Gynecol Cancer 2000; 10: 33–7

    Article  PubMed  Google Scholar 

  221. Gronlund B, Hogdall C, Hansen HH, et al. Performance status rather than age is the key prognostic factor in second-line treatment of elderly patients with epithelial ovarian carcinoma. Cancer 2002; 94: 1961–7

    Article  CAS  PubMed  Google Scholar 

  222. Dizon DS, Hensley ML, Poynor EA, et al. Retrospective analysis of carboplatin and paclitaxel as initial second-line therapy for recurrent epithelial ovarian carcinoma: application toward a dynamic disease state model of ovarian cancer. J Clin Oncol 2002; 20: 1238–47

    Article  CAS  PubMed  Google Scholar 

  223. Ozols RF. Recurrent ovarian cancer: evidence-based treatment. J Clin Oncol 2002; 20: 1161–3

    PubMed  Google Scholar 

  224. Homesley HD, Hall DJ, Martin DA, et al. A dose-escalating study of weekly bolus topotecan in previously treated ovarian cancer patients. Gynecol Oncol 2001; 83: 394–9

    Article  CAS  PubMed  Google Scholar 

  225. Seymour MT, Mansi JL, Gallagher CJ, et al. Protracted oral etoposide in epithelial ovarian cancer: a phase II study in patients with relapsed or platinum-resistant disease. Br J Cancer 1994; 69: 191–5

    Article  CAS  PubMed  Google Scholar 

  226. Clinical practice guidelines for the treatment of unresectable non-small-cell lung cancer. J Clin Oncol 1997; 15: 2996–3018

  227. Evans WK, Will BP, Berthelot JM, et al. The economics of lung cancer management in Canada. Lung Cancer 1996; 14: 19–29

    Article  CAS  PubMed  Google Scholar 

  228. Cullen MH, Billingham LJ, Woodroffe CM, et al. Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life. J Clin Oncol 1999; 17: 3188–94

    CAS  PubMed  Google Scholar 

  229. Non-small Cell Lung Cancer Collaborative Group. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. BMJ 1995; 311: 899–909

    Article  Google Scholar 

  230. Bunn PA Jr. Chemotherapy for advanced non-small-cell lung cancer: who, what, when, why? J Clin Oncol 2002; 20(18s): 23s–33s

    CAS  PubMed  Google Scholar 

  231. Elderly Lung Cancer Vinorelbine Italian Study Group. Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small-cell lung cancer. J Natl Cancer Inst 1999; 91: 66–72

    Article  Google Scholar 

  232. Lilenbaum RC, Herndon J, List M, et al. Single-agent (sa) versus combination chemotherapy (cc) in advanced non-small cell lung cancer (NSCLC): a CALGB randomized trial of efficacy, quality of life (QOL), and cost-effectiveness [abstract]. Proc Annu Meet Am Soc Clin Oncol 2002; 21: 2a

    Google Scholar 

  233. Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002; 346: 92–8

    Article  CAS  PubMed  Google Scholar 

  234. Trimble EL, Carter CL, Cain D, et al. Representation of older patients in cancer treatment trials. Cancer 1994; 74: 2208–14

    Article  CAS  PubMed  Google Scholar 

  235. Lichtman SM. Integration of geriatrics in oncology training: the relationship between the academic center and the community. Crit Rev Oncol Hematol 2000; 33: 57–9

    Article  CAS  PubMed  Google Scholar 

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  1. Don Monti Division of Medical Oncology, North Shore University Hospital, NYU School of Medicine, Manhasset, New York, USA

    Veena John, Sandeep Mashru &  Stuart M. Lichtman

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John, V., Mashru, S. & Lichtman, S.M. Pharmacological Factors Influencing Anticancer Drug Selection in the Elderly. Drugs Aging 20, 737–759 (2003). https://doi.org/10.2165/00002512-200320100-00003

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