Skip to main content
SpringerLink
Log in

Risks and Benefits of Taxanes in Breast and Ovarian Cancer

  • Review Article
  • Published:
Drug Safety Aims and scope Submit manuscript

Abstract

The taxanes are a unique class of agents with a broad spectrum of clinical activity. They act by binding to tubulin, producing unnaturally stable microtubules and subsequent cell death.

The distribution and elimination of paclitaxel depend on dose and administration rate. This nonlinearity is much less evident at lower infusion rates (24-hour infusions) and more evident at high plasma concentrations (3-hour infusions). The pharmacokinetics of docetaxel also suggest the presence of nonlinear pathways, but these appear to be clinically insignificant at the current doses utilised (60 to 100 mg/m2). Both agents undergo hepatic metabolism and biliary excretion and require dose adjustment in the setting of liver dysfunction. Drug interactions are quite common with these agents, some of which are sequence-dependent and clinically significant.

The optimal dose of paclitaxel is not known at this time, and controversy over possible dose- or schedule-related differences in efficacy still remain. Docetaxel is somewhat more consistent in its dose and scheduling information, but controversy remains regarding a dose-benefit relationship as well as scheduling differences (weekly vs every 3 weeks).

Toxicity profiles for these agents are somewhat different. Paclitaxel is more likely to be associated with peripheral neuropathy and myalgias/arthralgias than docetaxel. Docetaxel is more likely to be associated with a cumulative fluid retention syndrome that can be dose limiting.

Paclitaxel and docetaxel are both highly active agents against breast cancer, including tumours that are resistant to anthracyclines. Docetaxel tends to have higher response rates overall, but direct comparisons at maximally tolerated doses have not been completed. Combination regimens with many different agents are attempting to improve on the responses seen with single-agent taxanes.

The combination of paclitaxel and a platinum compound should be utilised as first-line therapy of advanced ovarian cancer. Controversy lies in the choice of the platinum compound and the dose and administration schedule of paclitaxel. Substitution of docetaxel for paclitaxel in these platinum-containing regimens is also being investigated. The taxanes also exhibit activity against ovarian cancer in patients previously exposed to platinum agents. These agents may also be administered intraperitoneally for local therapy of metastatic ovarian cancer.

Although docetaxel and paclitaxel are often considered similar in activity and tolerability, this review emphasises the fact that these agents are indeed different. Clinicians need to be familiar with the benefits and adverse events related to each agent in order to make informed, appropriate clinical decisions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Table III
Table IV
Table V
Table VI
Table VII

Similar content being viewed by others

References

  1. Wani MC, Taylor HL, Wall ME, et al. Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc 1971; 93: 2325–7

    PubMed  CAS  Google Scholar 

  2. Schiff PB, Fant J, Horowitz SB. Promotion of microtubule assembly in vitro by taxol. Nature 1979; 22: 665–7

    Google Scholar 

  3. Verweij J, Clavel M, Chevalier B. Paclitaxel (Taxol) and docetaxel (Taxotere): not simply two of a kind. Ann Oncol 1994; 5: 495–505

    PubMed  CAS  Google Scholar 

  4. Mangatal L, Adeline MT, Guenard D, et al. Application of the vicinal oxymination reaction with asymmetric induction to the hemisynthesis of taxol and analogues. Tetrahedron 1989; 45: 177–90

    Google Scholar 

  5. Stierle A, Strobel G, Stierle D. Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of pacific yew. Science 1993; 260: 214–6

    PubMed  CAS  Google Scholar 

  6. Jamis-Dow CA, Klecker RW, Katki AG, et al. Metabolism of taxol by human and rat liver in vitro: a screen for drug interactions and interspecies differences. Cancer Chemother Pharmacol 1995; 36: 107–14

    PubMed  CAS  Google Scholar 

  7. Woodcock DM, Jefferson S, Linsenmeyer ME, et al. Reversal of the multidrug resistance phenotype with Cremophor EL, a common vehicle for water-insoluble vitamins and drugs. Cancer Res 1990; 50: 4199–203

    PubMed  CAS  Google Scholar 

  8. Sharma A, Mayhew E, Bolcsak, et al. Activity of paclitaxel liposome formulations against human ovarian tumor xenografts. Int J Cancer 1997; 71: 103–7

    PubMed  CAS  Google Scholar 

  9. Cabanes A, Briggs KE, Gokhale PC, et al. Comparative in vivo studies with paclitaxel and liposome-encapsulated paclitaxel. Int J Cancer 1998; 12: 1035–40

    CAS  Google Scholar 

  10. Greenwald RB, Gilbert CW, Pendri A, et al. Drug delivery systems: water soluble taxol 2’-poly(ethylene glycol) ester prodrugs — design and in vivo effectiveness. J Med Chem 1996; 39: 424–31

    PubMed  CAS  Google Scholar 

  11. Zhang X, Burt HM, Mangold G, et al. Anti-tumor efficacy and biodistribution of intravenous polymeric micellar paclitaxel. Anti Cancer Drugs 1997; 8: 696–701

    PubMed  CAS  Google Scholar 

  12. Zhang X, Burt HM, VonHoff D, et al. An investigation of the antitumor activity and biodistribution of polymeric micellar paclitaxel. Cancer Chemother Pharmacol 1997; 40: 81–6

    PubMed  CAS  Google Scholar 

  13. Mamber SW, Mikkilineni AB, Pack EJ, et al. Tubulin polymerization by paclitaxel (Taxol) phosphate prodrugs after metabolic activation with alkaline phosphatase. J Pharmacol Exp Ther 1995; 274: 877–83

    PubMed  CAS  Google Scholar 

  14. Alder JD, Jarvis KP, Marsh KC, et al. Preclinical in vivo efficacy of two 9-dihydrotaxane analogues against human and murine tumours. Br J Cancer 1996; 73: 560–4

    PubMed  CAS  Google Scholar 

  15. Sparreboom A, van Asperen J, Mayer U, et al. Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by p-glycoprotein in the intestine. Proc Natl Acad Sci USA 1997; 94: 2031–5

    PubMed  CAS  Google Scholar 

  16. van Asperen J, van Tellingen O, Sparrebom A, et al. Enhanced oral bioavailability of paclitaxel in mice treated with the pglycoprotein blocker SDZ PSC 833. Br J Cancer 1997; 76 (9): 1181–3

    PubMed  Google Scholar 

  17. Malingre MM, Terwogt JM, Beijnen JH, et al. Phase I and pharmacokinetic study of oral paclitaxel. J Clin Oncol 2000; 18 (12): 2468–75

    PubMed  CAS  Google Scholar 

  18. Richel DJ, Malingre MM, ten Bokkel Huinink WW, et al. Cyclosporin a strongly enhances the oral bioavailability of docetaxel in cancer patients [meeting abstract]. Proc Annu Meet Am Soc Clin Oncol 1999; 18: A775

    Google Scholar 

  19. Extra JM, Rousseau F, Bruno R, et al. Phase I and pharmacokinetic study of Taxotere (RP 56976; NSC 628503) given as a short intravenous infusion. Cancer Res 1993; 53: 1037–42

    PubMed  CAS  Google Scholar 

  20. Burris H, Irvin R, Kuhn J, et al. Phase I clinical trial of Taxotere administered as either a 2-hour or 6-hour intravenous infusion. J Clin Oncol 1993; 11: 950–8

    PubMed  CAS  Google Scholar 

  21. Pazdur R, Newman RA, Newman BM, et al. Phase I trial of taxotere: five-day schedule. J Natl Cancer Inst 1992; 84: 1781–8

    PubMed  CAS  Google Scholar 

  22. Tomiak E, Piccart MJ, Kerger J, et al. Phase I study of docetaxel administered as a 1-hour intravenous infusion on a weekly basis. J Clin Oncol 1993; 12: 1458–67

    Google Scholar 

  23. Shelley WB, Talanin N, Shelley ED. Polysorbate 80 hypersensitivity. Lancet 1995; 345: 1312–3

    PubMed  CAS  Google Scholar 

  24. Gan Y, Wientjes MG, Lu J, et al. Cytostatic and apoptotic effects of paclitaxel in human breast tumors. Cancer Chemother Pharmacol 1998; 42 (3): 177–82

    PubMed  CAS  Google Scholar 

  25. Torres K, Horwitz SB. Mechanisms of Taxol-induced cell death are concentration dependent. Cancer Res 1998; 58 (16): 3620–6

    PubMed  CAS  Google Scholar 

  26. Rao S, Krauss NE, Heerding JM, et al. 3’-(p-azidobenzamido) taxol photolabels the N-terminal 31 amino acids of p-ttubulin. J Biol Chem 1994; 269: 3132–4

    PubMed  CAS  Google Scholar 

  27. Roberts JR, Rowinsky EK, Donehower RC. Demonstration of the cell cycle positions for taxol-induced ‘asters’ and ‘bundles’ by measurement of fluorescence, Feulgen-DNA content, and autoradiographic labeling of the same cells. J Histochem Cytochem 1989; 37: 1659–65

    PubMed  CAS  Google Scholar 

  28. Roberts JR, Allison DC, Donehower RC, et al. Development of polyploidization in taxol-resistant human leukemic cells in vitro. Cancer Res 1990; 50: 710–6

    PubMed  CAS  Google Scholar 

  29. Horwitz SB. Mechanism of action of taxol. Trends Pharmacol Sci 1992; 1: 134–6

    Google Scholar 

  30. Bhalla K, Ibrado AM, Tourkina E, et al. Taxol induces inter-nucleosomal DNA fragmentation associated with programmed cell death in human myeloid leukemia cells. Leukemia 1993; 7: 563–8

    PubMed  CAS  Google Scholar 

  31. Riou JF, Naudin A, Lavelle F. Effects of Taxotere on murine and human tumor cell lines. Biochem Biophys Res Commun 1992; 30: 444–50

    Google Scholar 

  32. Riou JF, Petitgenet O, Combeau C, et al. Cellular uptake and efflux of docetaxel (Taxotere®) and paclitaxel (Taxol®) in P388 cell line [abstract]. Proc Annu Meet Am Assoc Cancer Res 1994; 35: 385

    Google Scholar 

  33. Pazdur R, Kudelka AP, Kavanagh JJ, et al. The taxoids: paclitaxel (Taxol®) and docetaxel (Taxotere®). Cancer Treat Rev 1993; 19: 351–86

    PubMed  CAS  Google Scholar 

  34. Andreu JM, Diaz JF, Gil R, et al. Solution structure of taxotere-induced microtubules to 3-nm resolution: the change in protofilament number is linked to the binding of the taxol side chain. J Biol Chem 1994; 269 (50): 31785–92

    PubMed  CAS  Google Scholar 

  35. Fromes Y, Gounon P, Bissery MC, et al. Differential effects of Taxol or Taxotere on Tau and MAP2 containing microtubules [abstract]. Proc Am Assoc Cancer Res 1992; 33: 551

    Google Scholar 

  36. Hennequin C, Giocanti N, Favaudon V. S-phase specificity of cell killing by docetaxel (Taxotere) in synchronised HeLa cells. Br J Cancer 1995; 71: 1194–8

    PubMed  CAS  Google Scholar 

  37. Basu A, Haldar S. Microtubule-damaging drugs triggered bcl2 phosphorylation — requirement of phosphorylation on both serine-70 and serine-87 residues of bcl2 protein. Int J Oncol 1998; 13 (4): 659–64

    PubMed  CAS  Google Scholar 

  38. Klauber N, Parangi S, Flynn E, et al. Inhibition of angiogenesis and breast cancer in mice by the microtubule inhibitors 2-methoxyestradiol and taxol. Cancer Res 1997; 57 (1): 81–6

    PubMed  CAS  Google Scholar 

  39. Gupta RS. Taxol resistant mutants of chinese hamster ovary cells: genetic, biochemical, and cross-resistance studies. J Cell Physiol 1983; 114: 137–44

    PubMed  CAS  Google Scholar 

  40. Riou JF, Petitgenet O, Aynie I, et al. Establishment and characterization of docetaxel (Taxotere) resistant human breast carcinoma (Calc18/TXT) and murine leukemic (P388/TXT) cell lines [abstract #399]. Proc Am Assoc Cancer Res 1994; 35: 2021

    Google Scholar 

  41. Cabral F, Wible L, Brenner S, et al. Taxol-requiring mutant of Chinese hamster ovary cells with impaired mitotic spindle assembly. J Cell Biol 1983; 97: 30–9

    PubMed  CAS  Google Scholar 

  42. Kavallaris M, Kuo DYS, Burkhart CA, et al. Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific beta-tubulin isotypes. J Clin Invest 1997; 100 (5): 1282–93

    PubMed  CAS  Google Scholar 

  43. Valero V, Jones SF, Von Hoff DD, et al. A phase II study of docetaxel in patients with paclitaxel-resistant metastatic breast cancer. J Clin Oncol 1998; 16 (10): 3362–8

    PubMed  CAS  Google Scholar 

  44. Slamon DJ, Godolphin W, Jones LA, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 1989; 244: 707

    PubMed  CAS  Google Scholar 

  45. Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER2/neu oncogene. Science 1987; 235: 177–82

    PubMed  CAS  Google Scholar 

  46. Yu D, Liu B, Tan M, et al. Overexpression of c-erbB-2/neu in breast cancer cells confers increased resistance to Taxol via mdr-1-independent mechanisms. Oncogene 1996; 13 (6): 1359–65

    PubMed  CAS  Google Scholar 

  47. Yu D, Liu B, Jing T, et al. Overexpression of both p185c-erbB2 and p170mdr-1 renders breast cancer cells highly resistant to taxol. Oncogene 1998; 16 (16): 2087–94

    PubMed  CAS  Google Scholar 

  48. Product information: trastuzumab (Herceptin®). San Francisco: Genentech, Inc., September 1998

  49. Huizing MT, Keung ACF, Rosing H, et al. Pharmacokinetics of paclitaxel and metabolites in a randomized comparative study in platinum-pretreated ovarian cancer patients. J Clin Oncol 1993; 11 (11): 2127–35

    PubMed  CAS  Google Scholar 

  50. Brown T, Havlin K, Weiss G, et al. Aphase I trial of taxol given by 6-hour intravenous infusion. J Clin Oncol 1991; 9 (7): 1261–7

    PubMed  CAS  Google Scholar 

  51. Wilson WH, Berg S, Bryant G, et al. Paclitaxel in doxorubicin-refractory or mitoxantrone-refractory breast cancer: a phase I/II trial of 96-hour infusion. J Clin Oncol 1994; 12 (8): 1621–9

    PubMed  CAS  Google Scholar 

  52. 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 (1): 187–96

    PubMed  CAS  Google Scholar 

  53. Sonnichsen DS, Hurwitz CA, Pratt CB, et al. Saturable pharmacokinetics and paclitaxel pharmacodynamics in children with solid tumors. J Clin Oncol 1994; 12: 532–8

    PubMed  CAS  Google Scholar 

  54. Gianni L, Kearns CM, Giani A, et al. Nonlinear pharmacokinetics and metabolism of paclitaxel and its pharmacokinetic/pharmacodynamic relationships in humans. J Clin Oncol 1995; 13: 180–90

    PubMed  CAS  Google Scholar 

  55. Bissett D, Setanoians A, Cassidy J, et al. Phase I and pharmacokinetic study of Taxotere (RP 56976) administered as a 24-hour infusion. Cancer Res 1993; 53: 523–7

    PubMed  CAS  Google Scholar 

  56. McLeod HL, Kearns CM, Kuhn JG, et al. Evaluation of the linearity of docetaxel pharmacokinetics. Cancer Chemother Pharmacol 1998; 42: 155–9

    PubMed  CAS  Google Scholar 

  57. Sparreboom A, Tellingen O, van Nooijen WJ, et al. Nonlinear pharmacokinetics of paclitaxel in mice results from the pharmaceutical vehicle Cremophor EL. Cancer Res 1996; 56: 2112–5

    PubMed  CAS  Google Scholar 

  58. Royer I, Monsarrat B, Sonnier M, et al. Metabolism of docetaxel by human cytochrome P450: interactions with paclitaxel and other antineoplastic drugs. Cancer Res 1996; 56: 58–6

    PubMed  CAS  Google Scholar 

  59. Rowinsky EK, Gilbert MR, McGuire WP, et al. Sequences of taxol and cisplatin: a phase I and pharmacologic study. J Clin Oncol 1991; 9 (9): 1692–703

    PubMed  CAS  Google Scholar 

  60. Holmes FA, Madden T, Newman RA, et al. Sequence-dependent alteration of doxorubicin pharmacokinetics by paclitaxel in a phase I study of paclitaxel and doxorubicin in patients with metastatic breast cancer. J Clin Oncol 1996; 14 (10): 2713–21

    PubMed  CAS  Google Scholar 

  61. Gianni L, Vigano L, Locatelli A, et al. Human pharmacokinetic characterization and in vitro study of the interaction between doxorubicin and paclitaxel in patients with breast cancer. J Clin Oncol 1997; 15 (5): 1906–15

    PubMed  CAS  Google Scholar 

  62. Belani CP. Docetaxel in combination with platinums in patients with advanced non-small-cell lung cancer. Oncology 1997; 11 (8 Suppl.8): S42–S45

    Google Scholar 

  63. Dieras V. Review of docetaxel/doxorubicin combination in metastatic breast cancer. Oncology 1997; 11 (8 Suppl. 8): S31–S33

    Google Scholar 

  64. Ohtsu T, Sasaki Y, Tamura T, et al. Clinical pharmacokinetics and pharmacodynamics of paclitaxel: a 3-hour infusion versus a 24-hour infusion. Clin Cancer Res 1995; 1: 599–606

    PubMed  CAS  Google Scholar 

  65. Wiernik PH, Schwartz EL, Einzig A, et al. Phase I clinical and pharmacokinetic study of Taxol. Cancer Res 1987; 47: 2486–93

    PubMed  CAS  Google Scholar 

  66. Huizing MT, Vermorken JB, Rosing H, et al. Pharmacokinetics of paclitaxel and three major metabolites in patients with advanced breast carcinoma refractory to anthracycline therapy treated with a 3-hour paclitaxel infusion: a European Cancer Centre (ECC) trial. Ann Oncol 1995; 6: 699–704

    PubMed  CAS  Google Scholar 

  67. Product information: paclitaxel (Taxol®). Princeton: Bristol Myers-Squibb, Jan 2000

  68. Seidman AD, Hochhauser D, Gollub M, et al. Ninety-six-hour paclitaxel infusion after progression during short taxane exposure: a phase II pharmacokinetic and pharmacodynamic study in metastatic breast cancer. J Clin Oncol 1996; 14: 1877–84

    PubMed  CAS  Google Scholar 

  69. Smith RE, Brown AM, Mamounas E, et al. Randomized trial of 3-hour versus 24-hour infusion of high-dose paclitaxel in patients with metastatic or locally advanced breast cancer: National Surgical Adjuvant Breast and Bowel Project protocol B-26. J Clin Oncol 1999; 17 (11): 3403–11

    PubMed  CAS  Google Scholar 

  70. Holmes FA, Valero V, Buzdar A, et al. Final results: randomized phase III trial of paclitaxel by 3-hr versus 96-hr infusion in patients (PT) with metastatic breast cancer (MBC) [abstract #426]. Proc Annu Meet Am Soc Clin Oncol 1998; 17: 110a

    Google Scholar 

  71. Trissel LA, Xu Q, Martinez JF. Compounding an extended-stability admixture of paclitaxel for long-term infusion. Int J Pharmaceut Compounding 1997; 1 (1): 49–53

    Google Scholar 

  72. Horikoshi N, Inoue K, Aiba K, et al. Phase I study of paclitaxel [abstract]. Jpn J Cancer Chemother 1994; 21 (14): 2407–14

    CAS  Google Scholar 

  73. Winer E, Berry D, Duggan D, et al. Failure of higher dose paclitaxel to improve outcome in patient with metastatic breast cancer — results from CALGB 9342 [abstract #388]. Proc Annu Meet Am Soc Clin Oncol 1998; 17: 101a

    Google Scholar 

  74. Breier S, Lebedinsky C, Pelayes L, et al. Phase I/II weekly paclitaxel (P) 80 mg/m2 in pretreated patients (pts) with breast (BC) and ovarian cancer (OC) [abstract #568]. Proc Annu Meet Am Soc Clin Oncol 1997; 16: 163a

    Google Scholar 

  75. Seidman AD, Hudis CA, Albanel J, et al. Dose-dense therapy with weekly 1-hour paclitaxel infusions in the treatment of metastatic breast cancer. J Clin Oncol 1998; 16 (10): 3353–61

    PubMed  CAS  Google Scholar 

  76. Akerley W, Sikov WM, Cummings F, et al. Weekly high-dose paclitaxel in metastatic and locally advanced breast cancer: a preliminary report. Semin Oncol 1997; 24 (5 Suppl. 17): 87–90

    CAS  Google Scholar 

  77. Product information: docetaxel (Taxotere®). Rhone-Poulenc Rorer, July 1998

  78. Fulton G, Spencer CM. Docetaxel: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the management of metastatic breast cancer. Drugs 1996; 51 (6): 1075–92

    PubMed  CAS  Google Scholar 

  79. Valero V. Docetaxel as single-agent therapy in metastatic breast cancer: clinical efficacy. Semin Oncol 1997: 24 (4 Suppl. 13): 11–18

    Google Scholar 

  80. Valero V, Holmes FA, Walters RS, et al. Phase II trial of docetaxel: a new, highly effective antineoplastic agent in the management of patients with anthracycline-resistant metastatic breast cancer. J Clin Oncol 1995; 13: 2886–94

    PubMed  CAS  Google Scholar 

  81. 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: 2164–8

    PubMed  CAS  Google Scholar 

  82. 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 (5): 1811–9

    PubMed  CAS  Google Scholar 

  83. Markman M, Kennedy A, Webster K, et al. An effective and more convenient drug regimen for prophylaxis against paclitaxel-associated hypersensitivity reactions. J Cancer Res Clin Oncol 1999 Jul; 125 (7): 427–9

    PubMed  CAS  Google Scholar 

  84. Huang K, Vaughn DJ, Shaw LM, et al. A phase II trial and pharmacokinetic analysis of 96-hour infusional paclitaxel in patients with metastatic colorectal cancer. Am J Clin Oncol 1998; 21 (6): 548–52

    PubMed  CAS  Google Scholar 

  85. Riva A, Fumoleau P, Roche H, et al. Efficacy and safety of different corticosteroid (C) premedications (P) in breast cancer (BC) patients (pts) treated with Taxotere® (T) [abstract #660]. Proc Annu Meet Am Soc Clin Oncol 1997; 16: 188a

    Google Scholar 

  86. Holmes FA, Valero V, Walters RS, et al. The M.D. Anderson Cancer Center experience with taxol in metastatic breast cancer. Monogr Natl Cancer Inst 1993; 15: 161–9

    PubMed  Google Scholar 

  87. Seidman AD, Tiersten A, Hudis C, et al. Phase II trial of paclitaxel by 3-hour infusion as initial and salvage chemotherapy for metastatic breast cancer. J Clin Oncol 1995; 13: 2575–81

    PubMed  CAS  Google Scholar 

  88. Holmes FA, Valero V, Walters R, et al. Phase III trial of paclitaxel (P) administered over 3- or 96-HR for metastatic breast cancer (MBC) [abstract #91]. Proc Annu Meet Am Soc Clin Oncol 1996; 15: 106

    Google Scholar 

  89. Greco FA, Hainsworth JD. Paclitaxel (Taxol): Phase I/II trial comparing 1-hour infusion schedules. Semin Oncol 1994; 21 (5 Suppl. 8): S3–S8

    Google Scholar 

  90. American Society of Clinical Oncology. Update of recommendations for the use of hematopoietic colony-stimulating factors: evidenced-based clinical practice guidelines. J Clin Oncol 1996; 14 (6): 1957–60

    Google Scholar 

  91. Bishop JF, Dewar J, Toner GC, et al. Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer. J Clin Oncol 1999; 17 (8): 2355–64

    PubMed  CAS  Google Scholar 

  92. Fumoleau P, Chevallier B, Dieras V, et al. Safety evaluation of two doses of Taxotere (docetaxel) without routine premedication as first line in advanced breast cancer (ABC) — EORTC Clinical Screening Group (CSG) report [abstract #237]. Pro Annu Meet Am Soc Clin Oncol 1994; 13: 109

    Google Scholar 

  93. Engels EA, Lau J, Barza M. Efficacy of quinolone prophylaxis in neutropenic cancer patients: a meta-analysis. J Clin Oncol 1998; 16 (3): 1179–87

    PubMed  CAS  Google Scholar 

  94. Ravdin PM, Burris HA, Cook G, et al. Phase II trial of docetaxel in advanced anthracycline-resistant or anthracenedione-resistant breast cancer. J Clin Oncol 1995; 13 (12): 2879–85

    PubMed  CAS  Google Scholar 

  95. Bicher A, Levenback C, Burke TW, et al. Infusion site soft-tissue injury after paclitaxel administration. Cancer 1995; 76: 116–20

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  97. Ravdin P, Valero V, Nabholtz JM, et al. Efficacy of a 5-day corticosteroid premedication in ameliorating Taxotere induced fluid retention [abstract #124]. Proc Annu Meet Am Soc Clin Oncol 1996; 15: 115

    Google Scholar 

  98. Weiss RB, Donehower RC, Wiernik PH, et al. Hypersensitivity reactions from Taxol. J Clin Oncol 1990; 8 (7): 1263–8

    PubMed  CAS  Google Scholar 

  99. Peereboom DM, Donehower RC, Eisenhauer EA, et al. Successful re-treatment with Taxol after major hypersensitivity reactions. J Clin Oncol 1993; 11 (5): 885–90

    PubMed  CAS  Google Scholar 

  100. Laskin MS, Lucchesi KJ, Morgan M. Paclitaxel rechallenge failure after a major hypersensitivity reaction. J Clin Oncol 1993; 11 (12): 2456–8

    PubMed  CAS  Google Scholar 

  101. Rowinsky EK, McGuire WP, Guarnieri T, et al. Cardiac disturbances during the administration of taxol. J Clin Oncol 1991; 9: 1704–12

    PubMed  CAS  Google Scholar 

  102. Fisherman JS, Cowan KH, Noone M, et al. Phase I/II study of 72-hour infusional paclitaxel and doxorubicin with granulocyte colony-stimulating factor in patients with metastatic breast cancer. J Clin Oncol 1996; 14 (3): 774–82

    PubMed  CAS  Google Scholar 

  103. Pestalozzi BC, Sotos GA, Choyke PL, et al. Typhlitis resulting from treatment with taxol and doxorubicin in patients with metastatic breast cancer. Cancer 1993; 71: 1797–800

    PubMed  CAS  Google Scholar 

  104. Kennedy MJ, Zahurak ML, Donehower R, et al. Sequence-dependent hematologic toxicity associated with the 3-hour paclitaxel/cyclophosphamide doublet. Clin Cancer Res 1998; 4 (2): 349–56

    PubMed  CAS  Google Scholar 

  105. Cardenal F, Montes A, Llort G, et al. Typhlitis associated with docetaxel treatment. J Natl Cancer Inst 1996; 88 (15): 1078–9

    PubMed  CAS  Google Scholar 

  106. Seidman AD, Reichman BS, Crown JPA, et al. Paclitaxel as second and subsequent therapy for metastatic breast cancer: activity independent of prior anthracycline response. J Clin Oncol 1995; 13: 1152–9

    PubMed  CAS  Google Scholar 

  107. Gianni L, Capri G, Munzone E, et al. Paclitaxel efficacy in patients with advanced breast cancer resistant to anthracyclines. Semin Oncol 1994; 21Suppl. 8: S29–S33

    Google Scholar 

  108. Nabholtz JM, Gelmon K, Bontenbal M, et al. Multicenter, randomized comparative study of two doses of paclitaxel in patients with metastatic breast cancer. J Clin Oncol 1997; 14 (6): 1858–67

    Google Scholar 

  109. Eisenhauer EA, Vermorken JB. The taxoids: comparative clinical pharmacology and therapeutic potential. Drugs 1998; 55 (1): 5–30

    PubMed  CAS  Google Scholar 

  110. Paridaens R, Biganzoli L, Bruning P, et al. Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer: a European Organization for Research and Treatment of Cancer randomized study with cross-over. J Clin Oncol 2000; 18: 724–33

    PubMed  CAS  Google Scholar 

  111. Sledge GW, Neuberg D, Ingle J, et al. Phase III trial of doxorubicin (A) vs. paclitaxel (T) vs. doxorubicin + paclitaxel (A+T) as first-line therapy for metastatic breast cancer (MBC): an intergroup trial [abstract]. Proc Annu Meet Am Soc Clin Oncol 1997; 16: A2

    Google Scholar 

  112. Dieras V, Marty M, Tubiana N, et al. Phase II randomized study of paclitaxel versus mitomycin in advanced breast cancer. Semin Oncol 1995; 22 (4 Suppl. 8): S33–S39

    Google Scholar 

  113. Nabholtz JM, Senn HJ, Bezwoda WR, et al. Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. J Clin Oncol 1999; 17 (5): 1413–24

    PubMed  CAS  Google Scholar 

  114. Sjostrom J, Blomqvist C, Mouridsen H, et al. Docetaxel compared with sequential methotrexate and 5-fluorouracil in patients with advanced breast cancer after anthracycline failure: a randomised phase III study with crossover on progression by the Scandinavian Breast Group. Eur J Cancer 1999; 35 (8): 1194–201

    PubMed  CAS  Google Scholar 

  115. Chan S, Friedrichs K, Noel D, et al. Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. J Clin Oncol 1999; 17 (8): 2341–54

    PubMed  CAS  Google Scholar 

  116. Henderson IC, Berry D, Demetri G, et al. Improved disease-free (DFS) and overall survival (OS) from the addition of sequential paclitaxel (T) but not from the escalation of doxorubicin (A) dose level in the adjuvant chemotherapy of patients (PTS) with node-positive primary breast cancer (BC) [abstract #390A]. Proc Annu Meet Am Soc Clin Oncol 1998; 17: 101

    Google Scholar 

  117. Buzdar AU, Singletary SE, Theriault RL, et al. Prospective evaluation of paclitaxel versus combination chemotherapy with fluorouracil, doxorubicin, cyclophosphamide as neoadjuvant therapy in patients with operable breast cancer. J Clin Oncol 1999; 17 (11): 3412–7

    PubMed  CAS  Google Scholar 

  118. Holmes FA. Update: the M.D. Anderson Cancer Center experience with paclitaxel in the management of breast carcinoma. Semin Oncol 1995; 22Suppl. 8: S9–S15

    Google Scholar 

  119. O’Shaughnessy JA, Fisherman JS, Cowan KH. Combination paclitaxel (Taxol) and doxorubicin therapy for metastatic breast cancer (review). Semin Oncol 1994; 21Suppl. 8: S19–S23

    Google Scholar 

  120. Gianni L, Munzone E, Capri G, et al. Paclitaxel by 3-hour infusion in combination with bolus doxorubicin in women with untreated metastatic breast cancer: high antitumor efficacy and cardiac effects in a dose-finding and sequence-finding study. J Clin Oncol 1995; 13 (11): 2688–99

    PubMed  CAS  Google Scholar 

  121. Pouillart P, Fumoleau P, Romieu G, et al. Final results of a phase II randomized, parallel study of doxorubicin/cyclophosphamide (AC) and Doxorubicin/Taxol® (paclitaxel) (AT) as neoadjuvant treatment of local-regional breast cancer [abstract #275]. Proc Annu Meet Am Soc Clin Oncol 1999; 18: 73a

    Google Scholar 

  122. Penault-Liorca F, Sastre X, Fiche M, et al. Pathological response to neoadjuvant chemotherapy (CT): final results of a prospective randomized trial of 4AT vs 4AC as induction therapy in patients with operable breast cancer using Sataloff classification [abstract #248]. Breast Cancer Res Treat 1999; 57 (1): 67

    Google Scholar 

  123. Pluzanska A, Pienkowski T, Jelic S, et al. Phase III multicenter trial comparing taxol®/doxorubicin (AT) vs 5-fluorouracil/doxorubicin and cyclophosphamide (FAC) as a first line treatment for patients with metastatic breast cancer [abstract #21]. Breast Cancer Res Treat 1999; 57 (1): 30

    Google Scholar 

  124. Nabholtz JM, Falkson C, Campos D, et al. Doxorubicin and docetaxel (AT) is superior to standard doxorubicin and cyclophosphamide (AC) as 1st line CT for MBC: randomized phase III trial [abstract #330]. Breast Cancer Res Treat 1999; 57 (1): 84

    Google Scholar 

  125. Sparano JA, Speyer J, Gradishar WJ, et al. Phase I trial of escalating doses of paclitaxel plus doxorubicin and dexrazoxane in patients with advanced breast cancer. J Clin Oncol 1999; 17 (3): 880–6

    PubMed  CAS  Google Scholar 

  126. Dieras V. Docetaxel in combination with doxorubicin: a phase I dose-finding study. Oncology 1997; 11,6 Suppl. 6: S17–S20

    Google Scholar 

  127. Eisenhauer EA, ten Bokkel-Huinink WW, Swenerton KD, et al. European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: high-dose versus low-dose and long versus short infusion. J Clin Oncol 1994; 12: 2654–66

    PubMed  CAS  Google Scholar 

  128. 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

    PubMed  CAS  Google Scholar 

  129. Piccart MJ, Berthelson K, Stuart G, et al. Is cisplatin-paclitaxel (P-T) the standard in first-line treatment for advanced ovarian cancer (OVCA)? The EORTC-GCCG, NOCOVA, NCI-C and Scottish Intergroup experience [abstract #1258]. Proc Annu Meet Am Soc Clin Oncol 1997; 16: 352

    Google Scholar 

  130. Stuart G, Bertelsen K, Mangioni C, et al. Updated analysis shows a highly significant improved overall survival (OS) for cisplatin-paclitaxel as first line treatment of advanced ovarian cancer: mature results of the EORTC-GCCG, NOCOVA, NCIC CTG and Scottish Intergoup Trial [abstract]. Proc Annu Meet Am Soc Clin Oncol 1998; 17: 1394

    Google Scholar 

  131. du Bois A, Luck HJ, Bauknecht T, et al. Phase I/II study of the combination of carboplatin and paclitaxel as first-line chemotherapy in patients with advanced epithelial ovarian cancer. Ann Oncol 1997; 8: 355–61

    PubMed  Google Scholar 

  132. Bookmann MA, McGuire III WP, Kilpatrick D, et al. Carboplatin and paclitaxel in ovarian carcinoma: a phase I study of the Gynecologic Oncology Group. J Clin Oncol 1996; 14: 1895–902

    Google Scholar 

  133. Huizing MT, van Warmerdam LJC, Rosing H, et al. Phase I and pharmacologic study of the combination paclitaxel and carboplatin as first-line chemotherapy in stage III and IV ovarian cancer. J Clin Oncol 1997; 15: 1953–64

    PubMed  CAS  Google Scholar 

  134. ten Bokkel Huinink WW, van Warmerdam LJC, Helmerhorst TJ, et al. Phase II study of the combination carboplatin and paclitaxel in patients with ovarian cancer. Ann Oncol 1997; 8: 351–4

    PubMed  Google Scholar 

  135. Bolis G, Scarfone G, Zanaboni F, et al. A phase I-II trial of fixed-dose carboplatin and escalating paclitaxel in advanced ovarian cancer. Eur J Cancer 1997; 33: 592–5

    PubMed  CAS  Google Scholar 

  136. Siddiqui N, Boddy AV, Thomas HD, et al. A clinical and pharmacokinetic study of the combination of carboplatin and paclitaxel for epithelial ovarian cancer. Br J Cancer 1997; 75: 287–94

    PubMed  CAS  Google Scholar 

  137. Lhomme C, Kerbrat P, Lejeune C, et al. Carboplatin plus paclitaxel in the first-line treatment of advanced ovarian cancer: preliminary results of a phase I study. Semin Oncol 1996; 23Suppl. 12: S48–S54

    Google Scholar 

  138. Neijt JP, Hansen M, Hansen SW, et al. Randomized phase III study in previously untreated epithelial ovarian cancer FIGO stage IIB, IIC, III, IV, comparing paclitaxel-cisplatin and paclitaxel-carboplatin [abstract #1259]. Proc Annu Meet Am Soc Clin Oncol 1997; 16: 352a

    Google Scholar 

  139. du Bois A, Richter B, Warm M, et al. Cisplatin/paclitaxel vs carboplatin/paclitaxel as 1st-line treatment in ovarian cancer [abstract]. Proc Annu Meet Am Soc Clin Oncol 1998; 17: 1395

    Google Scholar 

  140. Muggia FM, Braly PS, Brady MF, et al. Phase III of cisplatin (P) or paclitaxel (T), versus their combination in suboptimal stage III and IV epithelial ovarian cancer (EOC): Gynecologic Oncology Group (GOG) study #132 [abstract #1257]. Proc Annu Meet Am Soc Clin Oncol 1997; 16: 352a

    Google Scholar 

  141. Guastalla JP, Ferrero JM, Dieras V, et al. Cisplatin-docetaxel (Taxotere) in first line treatment of advanced ovarian cancer (OC): a GINECO phase II trial [abstract #1448]. Proc Annu Meet Am Soc Clin Oncol 1999; 18: 375a

    Google Scholar 

  142. Jakobsen E, Bertelsen K, Madsen EL, et al. A phase II study in advanced ovarian cancer with Taxotere, cisplatinum & cyclophosphamide [abstract #1453]. Proc Annu Meet Am Soc Clin Oncol 1999; 18: 376a

    Google Scholar 

  143. Colombo N, Marzola M, Parma G, et al. Paclitaxel vs CAP (cyclophosphamide, Adriamycin, cisplatin) in recurrent platinum-sensitive ovarian cancer: a randomized phase II study [abstract #751]. Proc Annu Meet Am Soc Clin Oncol 1996; 15: 279

    Google Scholar 

  144. Ten Bokkel Huinink W, Gore M, Carmichael J, et al. Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer. J Clin Oncol 1997; 15: 2183–93

    PubMed  Google Scholar 

  145. Launois R, Reboul-Marty J, Henry B, et al. A cost-utility analysis of second-line chemotherapy in metastatic breast cancer: docetaxel versus paclitaxel versus vinorelbine. Pharmacoeconomics 1996; 10: 504–21

    PubMed  CAS  Google Scholar 

  146. Hutton J, Brown R, Borowitz M, et al. A new decision model for cost-utility comparisons of chemotherapy in recurrent metastatic breast cancer. Pharmacoeconomics 1996; 9Suppl. 2: S8–S22

    Google Scholar 

  147. Brown RE, Hutton J. Cost-utility model comparing docetaxel and paclitaxel in advanced breast cancer patients. Anticancer Drugs 1998; 9 (10): 899–907

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Breast Oncology, Division of Pharmacy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

    Laura Boehnke Michaud

  2. Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 56, Houston, Texas, 77030, USA

    Vicente Valero &  Gabriel Hortobagyi

Authors
  1. Laura Boehnke Michaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vicente Valero
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gabriel Hortobagyi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gabriel Hortobagyi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Michaud, L.B., Valero, V. & Hortobagyi, G. Risks and Benefits of Taxanes in Breast and Ovarian Cancer. Drug-Safety 23, 401–428 (2000). https://doi.org/10.2165/00002018-200023050-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-200023050-00005

Keywords

Search

Navigation