Medical Oncology

, Volume 20, Issue 3, pp 237–245 | Cite as

Protective effect of amifostine against toxicity of paclitaxel and carboplatin in non-small cell lung cancer

A single center randomized study
  • Ozkan KanatEmail author
  • Turkkan Evrensel
  • Ibrahim Baran
  • Hakan Coskun
  • Mehmet Zarifoglu
  • Omer Faruk Turan
  • Ender Kurt
  • Mutlu Demiray
  • Guzin Gonullu
  • Osman Manavoglu
Original Article


Aim: In this study we determined the protective role of amifostine against the side effects of the combination of paclitaxel and carboplatin in patients with non-small cell lung cancer (NSCLC).

Patients and Methods: Chemo-naive patients with NSCLC were eligible. Thirty-eight patients were randomized to receive paclitaxel 175 mg/m2 and carboplatin AUC=6 with amifostine 910 mg/m2 (group B) or chemotherapy alone (group A). The occurrences of hematologic, neurologic, cardiologic toxicities, and ototoxicity were evaluated.

Results: All patients completed the six scheduled cycles of therapy. A total of 114 cycles of chemotherapy was given in both groups. Neutropenia grade 3–4 was observed in 11 cycles (9.6%) in group A and 19 cycles (16.6%) in group B (p=0.16). Paresthesia grade 1 or 2 was observed in 18 of 19 patients of group A and in 8 of 19 patients of group B, following the sixth cycle of chemotherapy (p=0.018). Two patients of group B and nine patients of group A suffered from sensory motor impairment grade 2 (p=0.029). There was no clinical evidence in any patient for deterioration in cardiac function. Asymptomatic and transient sinus bradycardia or ventricular premature beats developed in four patients. None of the patients reported vertigo, tinnitus, or hearing loss.

Conclusion: The addition of the amifostine to the combination of paclitaxel and carboplatin may prevent or reduce the incidence of neurotoxicity in the treatment of NSCLC. Amifostine does not appear to have a preventive role in neutropenia.

Key Words

Amifostine paclitaxel carboplatin 


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  1. 1.
    Capizzi RL. Clinical status and optimal use of amifostine. Oncology 1999; 13:47–59.PubMedGoogle Scholar
  2. 2.
    Santini V, Giles F. The potential of amifostine: from cytoprotectant to therapeutic agent. Haemotologica 1999; 84:1035–1042.Google Scholar
  3. 3.
    Castiglione F, Porcile G, Gridelli C. The potential role of amifostine in the treatment of non-small cell lung cancer. Lung Cancer 2000; 39:57–66.CrossRefGoogle Scholar
  4. 4.
    Kemp G, et al. Amifostine pretreatment for protection against cyclophosphamide-induced and cisplatin-induced toxicities: results of a randomized control trial in patients with advanced ovarian cancer. J Clin Oncol 1996; 14:2101–2112.PubMedGoogle Scholar
  5. 5.
    Orditura M, et al. Amifostine: a selective cytoprotective agent of normal tissues from chemo-radiotherapy induced toxicity. Oncol Rep 1999; 6:1357–1362.PubMedGoogle Scholar
  6. 6.
    Griggs JJ. Reducing the toxicity of anticancer therapy: new strategies. Leukemia Research 1998; 22:27–33.CrossRefGoogle Scholar
  7. 7.
    Langer CJ, et al. Paclitaxel and carboplatin in combination in the treatment of advanced non-small cell lung cancer: A phase II toxicity, response, and survival analysis. J Clin Oncol 1995; 13:1860–1870.PubMedGoogle Scholar
  8. 8.
    Johnson DH, Paul DM, Hande KR, DeVore R. Paclitaxel plus carboplatin in the treatment of patients with advanced lung cancer: A Vanderbilt University Cancer Center phase II trial (LUN-46). Semin Oncol 1996; 23 (suppl 16):42–46.PubMedGoogle Scholar
  9. 9.
    Belani CP. Paclitaxel and docetaxel combinations in nonsmall lung cancer. Chest 2000; 117:144–151.CrossRefGoogle Scholar
  10. 10.
    Kosmidis P, et al. Paclitaxel and carboplatin in nonoperable non-small cell lung cancer. Semin Oncol 1996; 23 (suppl 15):16–18.PubMedGoogle Scholar
  11. 11.
    Kelly K, Pan Z, Murphy J, Huffman DH, Bunn PA, Jr. A phase I trial of paclitaxel plus carboplatin in untreated patients with advanced non-small cell lung cancer. Clin Cancer Res 1997; 3:1117–1123.PubMedGoogle Scholar
  12. 12.
    Belani CP. Incorporation of paclitaxel and carboplatin in combined-modality therapy for localy advanced non-small cell lung cancer. Semin Oncol 1999; 26 (suppl 2):44–54.PubMedGoogle Scholar
  13. 13.
    Greco FA, Hainsworth JD. Paclitaxel (1-hour infusion) plus carboplatin in the treatment of advanced non-small cell lung cancer: results of a multicenter phase II trial. Semin Oncol 1997; 24 (suppl 12):14–17.Google Scholar
  14. 14.
    Rowinsky EK, et al. Cardiac disturbances during the administration of Taxol. J Clin Oncol 1991; 9:1704–1712.PubMedGoogle Scholar
  15. 15.
    Shek TW, Luk IS, Ma L, Choung KL. Paclitaxel-induced cardiotoxicity. Arch Pathol Lab Med 1996; 120:89–91.PubMedGoogle Scholar
  16. 16.
    Jekunen A, Heikkila P, Maiche A, Pyrhonen S. Paclitaxel-induced myocardial damage detected by electron microscopy. Lancet 1994; 343:727–728. Letter.PubMedCrossRefGoogle Scholar
  17. 17.
    McGuire WP, et al. Taxol: A unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasmd. Ann Intern Med 1989; 111:273–279.PubMedGoogle Scholar
  18. 18.
    Ekholm EM, et al. Impairment of heart rate variability during paclitaxel therapy. Cancer 2000; 88:2149–2153.PubMedCrossRefGoogle Scholar
  19. 19.
    Laher S, Karp SJ. Acute myocardial infarction following paclitaxel administration for ovarian carcinoma. Clin Oncol 1997; 9:124–126.CrossRefGoogle Scholar
  20. 20.
    Kennedy IC, Fitzharris BM, Colls BM, Atkinson CH. Carboplatin is ototoxic. Cancer Chemother Pharmacol 1990; 26:232–234.PubMedCrossRefGoogle Scholar
  21. 21.
    Bauer FP, Westhoten M, Kehrl W. The ototoxicity of the cytostatic drug carboplatin in patients with head-neck tumors. Laryngorhinootologie 1992; 71:412–415.PubMedGoogle Scholar
  22. 22.
    Takeno S, Harrison RY, Mount RJ, Wake M, Harada Y. Induction of selective inner hair cell damage by carboplatin. Scanning Microsc 1994; 8:97–106.PubMedGoogle Scholar
  23. 23.
    Calvert AH, et al. Carboplatin dosage: prospect of evaluation of a simple formula based on renal function. J Clin Oncol 1989; 7:1748.PubMedGoogle Scholar
  24. 24.
    van der Vijgh WJ, Korst AE. Amifostine (Ethyol): pharmacokinetic and pharmacodynamic effects in vivo. Eur J Cancer 1996; 32:26–30.CrossRefGoogle Scholar
  25. 25.
    Buntzel J, Kuttner K, Frohlich D, Glatzel M. Selective cytoprotection with amifostine in concurrent radiochemotherapy for head and neck cancer. Ann Oncol 1998; 9:505–509.PubMedCrossRefGoogle Scholar
  26. 26.
    Schiller JH, et al. Amifostine, cisplatin and vinblastine in metastatic non small cell lung cancer: a report of high response rates and prolonged survival. J Clin Oncol 1996; 14:1913–1921.PubMedGoogle Scholar
  27. 27.
    Betticher DC, et al. Carboplatin combined with amifostine, a bone marrow protectant, in the treatment of non-small-cell lung cancer: a randomized phase II trial. Br J Cancer 1995; 72:1551–1555.PubMedGoogle Scholar
  28. 28.
    Gridelli C, et al. Amifostine plus cisplatin plus vinorelbine in the treatment of advanced non small cell lung cancer: a multicenter phase II study. Lung Cancer 2000; 28:237–244.PubMedCrossRefGoogle Scholar
  29. 29.
    Wozniak AJ, et al. Randomized trial comparing cisplatin with cisplatin plus vinorelbine in the treatment of advanced non-small-cell lung cancer: a Southwest Oncology Group study. J Clin Oncol 1998; 16:2459–2465.PubMedGoogle Scholar
  30. 30.
    DeVore III RF, Jagasia M, Johnson DH. Paclitaxel by either 1-hour or 24-hour infusion in combination with carboplatin in advanced non-small cell lung cancer: preliminary results comparing sequential phase II trials. Semin Oncol 1997; 24 (suppl 12):27–29.Google Scholar
  31. 31.
    Bunn PA. Combination paclitaxel and platinum in the treatment of lung cancer: US experience. Semin Oncol 1996; 23 (suppl 15):9–15.PubMedGoogle Scholar
  32. 32.
    Postma TJ, Vermorken JB, Liefting AJ, Pinedo HM, Heimans JJ. Paclitaxel-induced neuropathy. Ann Oncol 1995; 6:489–494.PubMedGoogle Scholar
  33. 33.
    DiPaola RS, et al. Amifostine and dose intense paclitaxel in patients with advanced malignancies. Cancer Ther 1998; 1:11–17.Google Scholar
  34. 34.
    Gelmon K, et al. Randomized phase II study of high-dose paclitaxel with or without amifostine in patients with metastatic breast cancer. J Clin Oncol 1999; 17:3038–3043.PubMedGoogle Scholar
  35. 35.
    Mitchell RB, Campbell WW, Jr. A phase II trial to ameliorate the neurotoxicity of carboplatin/paclitaxel for advanced non-small-cell lung cancer. Proc Am Soc Clin Oncol 1999; A2322.Google Scholar
  36. 36.
    Socinski MA, Tynan M, Natoli S, Steagall A. Gillenwater H. Phase II trial of paclitaxel and carboplatin and amifostine in stage IV non-small cell lung cancer (NSCLC). Proc Am Soc Clin Oncol 1999; A2015.Google Scholar
  37. 37.
    Fishman DA, Colhoun E, Golub R. Cost-utility assesment of amifostine in first-line therapy for ovarian cancer. Proc Am Soc Clin Oncol 1998; A417.Google Scholar

Copyright information

© Humana Press Inc 2003

Authors and Affiliations

  • Ozkan Kanat
    • 1
    Email author
  • Turkkan Evrensel
    • 1
  • Ibrahim Baran
    • 2
  • Hakan Coskun
    • 3
  • Mehmet Zarifoglu
    • 4
  • Omer Faruk Turan
    • 4
  • Ender Kurt
    • 1
  • Mutlu Demiray
    • 1
  • Guzin Gonullu
    • 1
  • Osman Manavoglu
    • 1
  1. 1.Uludag University Faculty of Medicine Department of Medical OncologyGorukle, BursaTurkey
  2. 2.Uludag University Faculty of Medicine Department of CardiologyGorukle, BursaTurkey
  3. 3.Uludag University Faculty of Medicine Department of OtorhinolaryngologyGorukle, BursaTurkey
  4. 4.Uludag University Faculty of Medicine Department of NeurologyGorukle, BursaTurkey

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