163
Views
28
CrossRef citations to date
0
Altmetric
Commentary

Optimising antiemetic therapy: what are the problems and how can they be overcome?

Pages 885-897 | Accepted 20 Apr 2005, Published online: 10 May 2005

References

  • Gralla RJ, Osoba D, Kris MG, et al. Recommendations for the use of antiemetics: evidence-based, clinical practice guidelines [American Society of Clinical Oncology]. J Clin Oncol 1999;17:2971–94
  • SHP therapeutic guidelines on the pharmacologic management of nausea and vomiting in adult and pediatric patients receiving chemotherapy or radiation therapy or undergoing surgery. Am J Health Syst Pharm 1999;56:729–64
  • Kris MG, Hesketh PJ, Herrstedt J, et al. Consensus proposals for the prevention of acute and delayed vomiting and nausea following high-emetic-risk chemotherapy. Supportive Care Cancer 2005;13(2):85–96
  • National Comprehensive Cancer Network©. NCCN clinical practice guidelines in oncology™: antiemesis. Version 1. 2004. www.nccn.org
  • Koeller JM, Aapro MS, Gralla RJ, et al. Antiemetic guidelines: creating a more practical treatment approach. Supportive Care Cancer 2002;10:519–22
  • Rittenberg CN. A new class of antiemetic agents on the horizon. Clin J Oncol Nurs 2002;6:103–4
  • Bender CM, McDaniel RW, Murphy-Ende K, et al. Chemotherapy-induced nausea and vomiting. Clin J Oncol Nurs 2002;6:94–102
  • Feyer PC, Stewart AL, Titlbach OJ. Aetiology and prevention of emesis induced by radiotherapy. Supportive Care Cancer 1998;6:253–60
  • Watcha MF, White PF. Postoperative nausea and vomiting. Its etiology, treatment, and prevention. Anesthesiology 1992;77: 162–84
  • Doherty KM. Closing the gap in prophylactic antiemetic therapy: patient factors in calculating the emetogenic potential of chemotherapy. Clin J Oncol Nurs 1999;3:113–9
  • Ritter Jr HL, Gralla RJ, Hall SW, et al. Efficacy of intravenous granisetron to control nausea and vomiting during multiple cycles of cisplatin-based chemotherapy. Cancer Invest 1998; 16:87–93
  • Laszlo J. Emesis as limiting toxicity in cancer chemotherapy. In: Laszlo J, editor. Antiemetics and cancer therapy. Baltimore/ London: Williams & Wilkins; 1983. p. 1–5
  • Henriksson R, Lomberg H, Israelsson G, Zackrisson B, Franzen L. The effect of ondansetron on radiation-induced emesis and diarrhoea. Acta Oncol 1992;31:767–9
  • Lindley C, Blower P. Oral serotonin type 3-receptor antagonists for prevention of chemotherapy-induced emesis. Am J Health-Syst Pharm 2000;57:1685–97
  • Andrews PLR, Davis CJ. The mechanism of emesis induced by anti-cancer agent therapies. In: Andrews PLR, Sanger GJ, editors. Emesis in anti-cancer therapy. London: Chapman and Hall; 1993. p. 113–61
  • DeVane CL. Substance P: a new era, a new role. Pharmacotherapy 2001;21:1061–9
  • Grelot L, Dapzol J, Esteve E, et al. Potent inhibition of both the acute and delayed emetic responses to cisplatin in piglets treated with GR205171, a novel highly selective tachykinin NK1 receptor antagonist. Br J Pharmacol 1998;124:1643–50
  • Matsumoto S, Kawasaki Y, Mikami M, et al. Relationship between cancer chemotherapeutic drug-induced delayed emesis and plasma levels of substance P in two patients with small cell lung cancer. Gan To Kagaku Ryoho 1999;26:535–8
  • Hesketh PJ. Comparative review of 5-HT3 receptor antagonists in the treatment of acute chemotherapy-induced nausea and vomiting. Cancer Invest 2000;18:163–73
  • Yalcin S, Tekuzman G, Baltali E, Ozisik Y, Barista I. Serotonin receptor antagonists in prophylaxis of acute and delayed emesis induced by moderately emetogenic, single-day chemotherapy: a randomized study. Am J Clin Oncol 1999;22:94–6
  • Constenla M. 5-HT3 receptor antagonists for prevention of late acute-onset emesis. Ann Pharmacother 2004;38(10):1683–91
  • Martin M. The severity and pattern of emesis following different cytotoxic agents. Oncology 1996;53(Suppl 1):26–31
  • Feyer P. Nausea und emesis in der Strahlentherapie. Im Focus Onkologie 2002;8:64–8
  • Aapro M. Methodological issues in antiemetic studies. Invest New Drugs 1993;11:243–53
  • Hesketh PJ, Kris MG, Grunberg SM, et al. Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol 1997;15:103–9
  • Roila F, Boschetti E, Tonato M, et al. Predictive factors of delayed emesis in cisplatin-treated patients and antiemetic activity and tolerability of metoclopramide or dexamethasone. A randomized single-blind study. Am J Clin Oncol 1991;14:238–42
  • Italian Group for Antiemetic Research. Ondansetron + dexamethasone vs metoclopramide + dexamethasone + diphenhydramine in prevention of cisplatin-induced emesis. Lancet 1992;340:96–9
  • Roila F. Ondansetron plus dexamethasone compared to the ‘standard’ metoclopramide combination. Oncology 1993;50:163–7
  • Aapro MS, Thuerlimann B, Sessa C, De Pree C, Bernhard J, Maibach R. A randomized double-blind trial to compare the clinical efficacy of granisetron with metoclopramide, both combined with dexamethasone in the prophylaxis of chemotherapy-induced delayed emesis. Ann Oncol 2003;14:291–7
  • Schnell FM. Chemotherapy-induced nausea and vomiting: the importance of acute antiemetic control. Oncologist 2003;8:187–98
  • Roila F, Del Favero A. Ondansetron clinical pharmacokinetics. Clin Pharmacokinet 1995;29:95–109
  • Carmichael J, Cantwell BM, Edwards CM, et al. A pharmacokinetic study of granisetron (BRL 43694A), a selective 5-HT3 receptor antagonist: correlation with anti-emetic response. Cancer Chemother Pharmacol 1989;24:45–9
  • Anzemet® (dolasetron mesylate). Aventis Pharmaceuticals Inc., Kansas City, MO, USA; 2000: Prescribing Information
  • Navoban® (tropisetron hydrochloride). Novartis New Zealand Ltd, Avondale, Auckland, New Zealand; 2001: Prescribing Information
  • Piraccini G, Stoltz R, Tei M, et al. Pharmacokinetic features of a novel 5-HT3-receptor antagonist: palonosetron (RS-25259–197). Proc Am Soc Clin Oncol 2001 [abstract 1595]
  • Kytril® tablets (granisetron hydrochloride) Prescribing Information. Nutley NJ, Roche Laboratories Inc 2000
  • Zofran® (ondansetron hydrochloride). North Chicago, IL, USA, Glaxo Wellcome 2000: Prescribing Information
  • Piraccini G, Gallagher SC, Macchiocchi A, et al. Palonosetron: a phase II dose ranging study to assess, over a 7-day period, the single-dose pharmacokinetic profile of palonosetron in patients receiving highly emetogenic chemotherapy. Proc Am Soc Clin Oncol 2002;21 [abstract 449]
  • Newberry NR, Watkins CJ, Sprosen TS, Blackburn TP, Grahame-Smith DG, Leslie RA. BRL 46470 potently antagonizes neural responses activated by 5-HT3 receptors. Neuropharmacology 1993;32: 729–35
  • Eisenberg P, MacKintosh F, Ritch P, Cornett P, Macciocchi A. Efficacy, safety and pharmacokinetics of palonosetron in patients receiving highly emetogenic cisplatin-based chemotherapy: a dose-ranging clinical study. Ann Oncol 2004;15:330–7
  • Gralla R, Lichinitser M, Van Der Vegt S, et al. Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol 2003;14:1570–7
  • Eisenberg P, Figueroa-Vadillo J, Zamora R, et al. Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist: results of a phase III, single-dose trial versus dolasetron. Cancer 2003;98:2473–82
  • Cohen L, de Moor C, Eisenberg P, et al. Delayed chemotherapy-induced nausea and vomiting remains a problem and significantly interferes with daily function in patients receiving emetogenic chemotherapy in the United States. Proc Am Soc Clin Oncol 2003;22:739 [abstract 2972]
  • Hesketh PJ, Van Belle S, Aapro M, et al. Differential involvement of neurotransmitters through the time course of cisplatin-induced emesis as revealed by therapy with specific receptor antagonists. Eur J Cancer 2003;39:1074–80
  • Navari R, Madajewicz S, Anderson N, et al. Oral ondansetron for the control of cisplatin-induced delayed emesis: a large, multicenter, double-blind randomized comparative trial of ondansetron versus placebo. J Clin Oncol 1995;13:2408–16
  • Tanihata S, Oda S, Kakuta S, Uchiyama T. Antiemetic effect of a tachykinin NK1 receptor antagonist GR205171 on cisplatin-induced early and delayed emesis in the pigeon. Eur J Pharmacol 2003;461:197–206
  • Campos D, Pereira JR, Reinhardt RR, et al. Prevention of cisplatin-induced emesis by the oral neurokinin-1 antagonist, MK-869, in combination with granisetron and dexamethasone or with dexamethasone alone. J Clin Oncol 2001;19:1759–67
  • Van Belle S, Lichinitser MR, Navari RM, et al. Prevention of cisplatin-induced acute and delayed emesis by the selective neurokinin-1 antagonists, L-758,298 and MK-869. Cancer 2002;94:3032–41
  • Warr D, Gralla R, Hesketh P, et al. The oral NK1 antagonist aprepitant for the prevention of chemotherapy induced nausea and vomiting: 2 randomized, double-blind, placebo controlled trials. Proc Am Soc Clin Oncol 2003;22:726 [abstract 2919]
  • de Wit R, Herrstedt J, Rapoport B, et al. The oral NK(1) antagonist, aprepitant, given with standard antiemetics provides protection against nausea and vomiting over multiple cycles of cisplatin-based chemotherapy: a combined analysis of two randomised, placebo-controlled phase III clinical trials. Eur J Cancer 2004;40:403–10
  • Warr DG, Eisenberg P, Hesketh PJ, et al. Phase III, double-blind study to assess an aprepitant-containing regimen for the prevention of nausea and vomiting due to moderately emetogenic chemotherapy. Proc Am Soc Clin Oncol 2004; [late-breaking abstract 8007]
  • Sanchez LA, Holdsworth M, Bartel SB. Stratified administration of serotonin 5-HT3 receptor antagonists (setrons) for chemotherapy-induced emesis. Economic implications. Pharmacoeconomics 2000;18: 533–56
  • Bubalo J, Seelig F, Karbowicz S, Maziarz RT. Randomized open-label trial of dolasetron for the control of nausea and vomiting associated with high-dose chemotherapy with hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2001;7:439–45
  • Grote TH, Pineda LF, Figlin RA, et al. Oral dolasetron mesylate in patients receiving moderately emetogenic platinum-containing chemotherapy [Oral Dolasetron Dose Response Study Group]. Cancer J Sci Am 1997;3:45–51
  • Mantovani G, Maccio A, Bianchi A, et al. Comparison of granisetron, ondansetron, and tropisetron in the prophylaxis of acute nausea and vomiting induced by cisplatin for the treatment of head and neck cancer: a randomized controlled trial. Cancer 1996;77:941–8
  • Marty M, Kleisbauer JP, Fournel P, et al. Is Navoban (tropisetron) as effective as Zofran (ondansetron) in cisplatin-induced emesis? [The French Navoban Study Group]. Anticancer Drugs 1995;6(Suppl 1):15–21
  • Chua DT, Sham JS, Kwong DL, et al. Comparative efficacy of three 5-HT3 antagonists (granisetron, ondansetron, and tropisetron) plus dexamethasone for the prevention of cisplatin-induced acute emesis: a randomized crossover study. Am J Clin Oncol 2000;23:185–91
  • Ruff P, Paska W, Goedhals L, et al. Ondansetron compared with granisetron in the prophylaxis of cisplatin-induced acute emesis: a multicentre double-blind, randomised, parallel-group study [The Ondansetron and Granisetron Emesis Study Group]. Oncology 1994;51:113–8
  • Italian Group for Antiemetic Research. Ondansetron versus granisetron, both combined with dexamethasone, in the prevention of cisplatin-induced emesis. Ann Oncol 1995; 6:805–10
  • Beck TM, Hesketh PJ, Madajewicz S, et al. Stratified, randomized, double-blind comparison of intravenous ondansetron administered as a multiple-dose regimen versus two single-dose regimens in the prevention of cisplatin-induced nausea and vomiting. J Clin Oncol 1992;10:1969–75
  • Jantunen IT, Muhonen TT, Kataja VV, Flander MK, Teerenhovi L. 5-HT3 receptor antagonists in the prophylaxis of acute vomiting induced by moderately emetogenic chemotherapy – a randomised study. Eur J Cancer 1993;29A:1669–72
  • Dempsey CL, Coop AJ, Shillington A, et al. Antiemetic effectiveness of ondansetron and granisetron in patients with breast cancer treated with cyclophosphamide. Am J Health-Syst Pharm 2004;61:781–6
  • Jordan K, Hinke A, Grothey A, et al. A meta-analysis comparing the efficacy of five 5-HT3-receptor antagonists (5-HT3-RAs) for acute chemotherapy-induced emesis. Proc Am Soc Clin Oncol 2004;23:737 [abstract 8048]
  • Abenhardt W, Hitz H, Völkl S, et al. Comparison of ondansetron 8mg (OND8) vs. granisetron 1 mg (GRA1) vs. granisetron 3 mg (GRA3) in the daily oncological practice. Supportive Care Cancer 2004;12:370 [abstract A–16]
  • Italian Group for Antiemetic Research. Randomized, double-blind, dose-finding study of dexamethasone in preventing acute emesis induced by anthracyclines, carboplatin, or cyclophosphamide. J Clin Oncol 2004;22:725–9
  • Italian Group for Antiemetic Research. Double-blind, dose-finding study of four intravenous doses of dexamethasone in the prevention of cisplatin-induced acute emesis. J Clin Oncol 1998;16:2937–42
  • Goldsmith B. Antiemetic patterns of care for radiotherapy-induced nausea and vomiting. Proc Am Soc Clin Oncol 2003;22:740 [abstract 2975]
  • Feyer P, Seegenschmiedt MH. Antiemetic patterns of care for radiotherapy-induced nausea and vomiting. Presented at the European Congress of Clinical Oncologists Annual Meeting, 2003. Abstract 929
  • Goodin S, Cunningham R. 5-HT(3)-receptor antagonists for the treatment of nausea and vomiting: a reappraisal of their side-effect profile. Oncologist 2002;7:424–36
  • Wood M. Pharmacokinetic drug interactions in anaesthetic practice. Clin Pharmacokinet 1991;21:285–307
  • Davis MP, Homsi J. The importance of cytochrome P450 monooxygenase CYP2D6 in palliative medicine. Supportive Care Cancer 2001;9:442–51
  • May FE, Stewart RB, Cluff LE. Drug interactions and multiple drug administration. Clin Pharmacol Ther 1977;22:322–8
  • Karas Jr S. The potential for drug interactions. Ann Emerg Med 1981;10:627–30
  • Riechelmann RP, Smaletz Ó, Saad ED. Drug interactions in cancer inpatients. Proc Am Soc Clin Oncol 2004 [abstract 8146]
  • Tucker GT. Advances in understanding drug metabolism and its contribution to variability in patient response. Ther Drug Monit 2000;22:110–3
  • Dixon CM, Colthup PV, Serabjit-Singh CJ, et al. Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. Drug Metab Dispos 1995;23: 1225–30
  • Firkusny L, Kroemer HK, Eichelbaum M. In vitro characterization of cytochrome P450 catalysed metabolism of the antiemetic tropisetron. Biochem Pharmacol 1995;49: 1777–84
  • Sanwald P, David M, Dow J. Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of dolasetron. Comparison with other indole-containing 5-HT3 antagonists. Drug Metab Dispos 1996;24: 602–9
  • Bloomer JC, Baldwin SJ, Smith GJ, Ayrton AD, Clarke SE, Chenery RJ. Characterisation of the cytochrome P450 enzymes involved in the in vitro metabolism of granisetron. Br J Clin Pharmacol 1994;38:557–66
  • Aloxi™ (palonosetron HCL injection) Prescribing Information. Cardinal Health, Albuquerque, NM, USA. Helsinn Birex Pharmaceuticals, Dublin, Ireland. Distributed by MGI Pharma Inc, Bloomington, MN, USA. July 2003
  • Herrstedt J. The development of a new 5-HT3 receptor antagonist: from pharmacology to clinics. Presented at the Multinational Association for Supportive Care in Cancer meeting, 18–21 June 2003, Berlin, Germany
  • Cagnoni PJ, Matthes S, Day TC, Bearman SI, Shpall EJ, Jones RB. Modification of the pharmacokinetics of high-dose cyclophosphamide and cisplatin by antiemetics. Bone Marrow Transplant 1999;24:1–4
  • Gilbert CJ, Petros WP, Vredenburgh J, et al. Pharmacokinetic interaction between ondansetron and cyclophosphamide during high-dose chemotherapy for breast cancer. Cancer Chemother Pharmacol 1998;42:497–503
  • Koriech OM. Fluoxetine treatment comprises the antiemetic efficacy of ondansetron in cancer patients. Clin Oncol (R Coll Radiol) 1995;7:371–2
  • Stanford BJ, Stanford SC. Postoperative delirium indicating an adverse drug interaction involving the selective serotonin reuptake inhibitor, paroxetine? J Psychopharmacol 1999;13:313–7
  • De Witte JL, Schoenmaekers B, Sessler DI, Deloof T. The analgesic efficacy of tramadol is impaired by concurrent administration of ondansetron. Anesth Analg 2001;92:1319–21
  • Kaiser R, Sezer O, Papies A, et al. Patient-tailored antiemetic treatment with 5-Hydroxytryptamine type 3 receptor antagonists according to cytochrome P-450 2D6 genotypes. J Clin Oncol 2002;20:2805–11
  • Emend® Merck & Co., Inc., Whitehouse Station, New Jersey, 2003. Prescribing information
  • Aprepitant FDA Advisory Committee Background Package, March 6, 2003. BG1037.doc Version 3.0 approved, January 31, 2003. Available from: www.fda.gov/ohrms/dockets/ac/03/ briefing/3928B1_01_Merck%20Backgrounder.pdf [accessed 21 June 2004)]
  • Chawla SP, Grunberg SM, Gralla RJ, et al. Establishing the dose of the oral NK1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting. Cancer 2003;97:2290–300
  • Blum RA, Majumdar A, McCrea J, et al. Effects of aprepitant on the pharmacokinetics of ondansetron and granisetron in healthy subjects. Clin Ther 2003;25:1407–19
  • Blower PR. 5-HT3-receptor antagonists and the cytochrome P450 system: clinical implications. Cancer J 2002;8:405–14
  • Gridelli C, Rossi A, Maione P. Polypharmacy in the elderly cancer patient – is there a risk? Presented at the 7th International Society of Geriatric Oncology Annual Meeting, 27–28 September 2002, Boston, MA, USA
  • Gridelli C, Perrone F, Gallo C, et al. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst 2003;95:362–72
  • Keefe DL. The cardiotoxic potential of the 5-HT(3) receptor antagonist antiemetics: is there cause for concern? Oncologist 2002;7:65–72
  • Lowenthal RM, Eaton K. Toxicity of chemotherapy. Hematol Oncol Clin North Am 1996;10:967–90
  • Adams MJ, Hardenbergh PH, Constine LS, Lipshultz SE. Radiation-associated cardiovascular disease. Crit Rev Oncol Hematol 2003;45:55–75
  • Algra A, Tijssen JG, Roelandt JR, Pool J, Lubsen J. QTc prolongation measured by standard 12-lead electrocardiography is an independent risk factor for sudden death due to cardiac arrest. Circulation 1991;83: 1888–94
  • Hunt TL, Cramer M, Shah A, Stewart W, Benedict CR, Hahne WF. A double-blind, placebo-controlled, dose-ranging safety evaluation of single-dose intravenous dolasetron in healthy male volunteers. J Clin Pharmacol 1995;35:705–12
  • Benedict CR, Arbogast R, Martin L, Patton L, Morrill B, Hahne W. Single-blind study of the effects of intravenous dolasetron mesylate versus ondansetron on electrocardiographic parameters in normal volunteers. J Cardiovasc Pharmacol 1996;28:53–9
  • Goodin S, Cunningham R. In reply: evidence for equivalent cardiotoxicity of the 5-HT3-receptor antagonists. Oncologist 2003;8:219–21
  • Boike SC, Ilson B, Zariffa N, Jorkasky DK. Cardiovascular effects of i.v. granisetron at two administration rates and of ondansetron in healthy adults. Am J Health-Syst Pharm 1997;54:1172–6
  • Upward JW, Arnold BD, Link C, Pierce DM, Allen A, Tasker TC. The clinical pharmacology of granisetron (BRL 43694), a novel specific 5-HT3 antagonist. Eur J Cancer 1990;26(Suppl 1): S12–5
  • Carmichael J, Harris AL. The cardiovascular safety of high-dose intravenous granisetron in cancer patients receiving highly emetogenic chemotherapy. Cancer Chemother Pharmacol 2004;53:123–8
  • Carmichael J, Harris AL. High-dose i.v. granisetron for the prevention of chemotherapy-induced emesis: cardiac safety and tolerability. Anticancer Drugs 2003;14:739–44
  • Aapro M, Bourke JP. Rapid intravenous administration of granisetron prior to chemotherapy is not arrythmogenic: results of a pilot study. Eur J Cancer 2003;39:927–31
  • Ashkanani F, Heys SD, Eremin O. The management of cancer in the elderly. J R Coll Surg Edinburgh 1999;44:2–10
  • Yancik R. Cancer burden in the aged: an epidemiologic and demographic overview. Cancer 1997;80:1273–83
  • Aapro M. 5-HT3 receptor antagonists and cardiovascular safety, an obvious issue in the elderly. Presented at the 7th International Society of Geriatric Oncology Annual Meeting, 27–28 September 2002, Boston, MA, USA
  • Orr WC, Chen CL. Aging and neural control of the GI tract: IV. Clinical and physiological aspects of gastrointestinal motility and aging. Am J Physiol Gastrointest Liver Physiol 2002;283: G1226–31
  • Schroder J, Kratz B, Pantel J, Minnemann E, Lehr U, Sauer H. Prevalence of mild cognitive impairment in an elderly community sample. J Neural Transm Suppl 1998;54:51–9
  • Yee KW, Pater JL, Pho L, Zee B, Siu LL. Enrollment of older patients in cancer treatment trials in Canada: why is age a barrier? J Clin Oncol 2003;21:1618–23
  • Aapro MS. How do we manage patients with refractory or breakthrough emesis? Supportive Care Cancer 2002; 10:106–9
  • Terrey J-P, Aapro MS. The activity of granisetron in patients who had previously failed ondansetron antiemetic therapy. Eur J Clin Res 1996;8:281–8
  • Carmichael J, Keizer HJ, Cupissol D, Milliez J, Scheidel P, Schindler AE. Use of granisetron in patients refractory to previous treatment with antiemetics. Anticancer Drugs 1998;9:381–5
  • de Wit R, de Boer AC, vd Linden GH, Stoter G, Sparreboom A, Verweij J. Effective cross-over to granisetron after failure to ondansetron, a randomized double blind study in patients failing ondansetron plus dexamethasone during the first 24 hours following highly emetogenic chemotherapy. Br J Cancer 2001;85:1099–101
  • de Wit R. Current position of 5HT3 antagonists and the additional value of NK1 antagonists; a new class of antiemetics. Br J Cancer 2003;88:1823–7
  • Blower P, Aapro M. Granisetron vs ondansetron: is it a question of duration of 5-HT3 receptor blockade? Br J Cancer 2002;86: 1662–3

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.