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Achieving Full-Dose, On-Schedule Administration of ACE Chemotherapy Every 14 Days for the Treatment of Patients with Extensive Small-Cell Lung Cancer

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Abstract

Extensive small-cell lung cancer (SCLC) is commonly treated with multiple cycles of chemotherapy. Reducing the time interval between cycles of chemotherapy (dose-dense chemotherapy) may improve outcomes in the treatment of extensive SCLC, as it has in other chemosensitive malignancies. To evaluate the feasibility of dose-dense chemotherapy in patients with extensive SCLC, this study evaluates a dose-dense doxorubicin/cyclophosphamide/etoposide (ACE) regimen, supported by the once-per-cycle administration of the hematopoietic growth factor pegfilgrastim. Patients received up to six 14-day cycles of ACE chemotherapy (doxorubicin 40 mg/m,2 cyclophosphamide 1000 mg/m2, etoposide 120 mg/m2 on day 1 IV, plus oral etoposide 240 mg/m2 daily on days 2–3). On day 4 of each cycle, patients received pegfilgrastim 6 mg by subcutaneous injection. Of 30 patients enrolled, 27 started chemotherapy and received pegfilgrastim. Full-dose, on-schedule chemotherapy was given to all 22 patients starting cycle 2, and in 107 (88%) of 121 cycles. Eighteen of the 27 patients (67%) received full-dose, on-schedule chemotherapy for all 6 cycles. The overall response rate was 17/27 (63%). Nine patients (33%) experienced hematologic toxicities that investigators considered severe or life-threatening. Four patients (15%) had febrile neutropenia. Full-dose, on-schedule dose-dense ACE chemotherapy is feasible with once-per-cycle pegfilgrastim support in extensive SCLC.

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References

  1. Ardizzoni A, Tjan-Heijnen VCG, Postmus PE, et al. (2002) Standard versus intensified chemotherapy with granylocyte colony-stimulating factor support in small-cell lung cancer: a prospective European Organization for Research and Treatment of Cancer—Lung Cancer Group Phase III Trial 08923. J Clin Oncol 20:3947–3955

    Article  PubMed  CAS  Google Scholar 

  2. Bentley MP, Norvath N, Lewis ID, et al. (2003) Single dose per cycle pegfilgrastim successfully supports full dose intensity CHOP-14 in patients over 60 years with non-Hodgldn’s lymphoma (NHL) and successfully mobilizes peripheral blood progenitor cells (PBPC). Blood 102:abstract 2348

    Google Scholar 

  3. Bonadonna G, Valagussa P, Moliterni A, Zambetti M, Brambilla C (1995) Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up. N Engl J Med 332:901–906

    Article  PubMed  CAS  Google Scholar 

  4. Budman DR, Berry DA, Cirrincione CT, et al. (1998) Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer. The Cancer and Leukemia Group B. J Natl Cancer Inst 90:1205–1211

    Article  PubMed  CAS  Google Scholar 

  5. Citron ML, Berry DA, Cirrincione C, et al. (2003) Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol 21:1431–1439

    Article  PubMed  CAS  Google Scholar 

  6. Crawford J, Ozer H, Stoller R, et al. (1991) Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. N Engl J Med 325:164–170

    Article  PubMed  CAS  Google Scholar 

  7. Dunlop DJ, Eatock MM, Paul J, et al. (1998) Randomized multicentre trial of filgrastim as an adjunct to combination chemotherapy for Hodgkin’s disease. West of Scotland Lymphoma Group. Clin Oncol (R Coll Radiol) 10:107–114

    CAS  Google Scholar 

  8. Epelbaum R, Faraggi D, Ben-Arie Y, et al. (1990) Survival of diffuse large cell lymphoma: a muitivariate analysis including dose intensity variables. Cancer 66:1124–1129

    Article  PubMed  CAS  Google Scholar 

  9. Green MD, Koelbl H, Baselga J, et al. (2003) A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy. Ann Oncol 14:29–35

    Article  PubMed  CAS  Google Scholar 

  10. Grigg A, Solal–Celigny P, Hoskin P, et al. (2003) Open-label, randomized study of pegfilgrastim vs. daily filgrastim as an adjunct to chemotherapy in elderly patients with non-Hodgkin’s lymphoma. Leuk Lymphoma 44:1503–1508

    Article  PubMed  CAS  Google Scholar 

  11. Holmes FA, Jones SE, O’Shaughnessy J, et al. (2002) Comparable efficacy and safety profiles of once-per-cycle pegfilgrastim and daily injection filgrastim in chemotherapy-induced neutropenia: a multicenter dose-finding study in women with breast cancer. Ann Oncol 13:903–909

    Article  PubMed  CAS  Google Scholar 

  12. Ihde DC (1995) Small cell lung cancer. State-of-the-art therapy 1994. Chest 107:243S–248S

    PubMed  CAS  Google Scholar 

  13. Ihde DC, Mulshine JL, Kramer BS, et al. (1994) Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer. J Clin Oncol 12:2022–2034

    PubMed  CAS  Google Scholar 

  14. Johnson DH, Einhorn LH, Birch R, et al. (1987) A randomized comparison of high-dose versus conventional-dose cyclophosphamide, doxorubicin, and vincristine for extensive-stage small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol 5:1731–1738

    PubMed  CAS  Google Scholar 

  15. Johnston E, Crawford J, Blackwell S, et al. (2000) Randomized, dose-escalation study of SD/01 compared with daily filgrastim in patients receiving chemotherapy. J Clin Oncol 18:2522–2528

    PubMed  CAS  Google Scholar 

  16. Kwak LW, Halpern J, Olshen RA, Horning SJ (1990) Prognostic significance of actual dose intensity in diffuse large-cell lymphoma: results of a tree-structured survival analysis. J Clin Oncol 8:963–977

    PubMed  CAS  Google Scholar 

  17. Lepage E, Gisselbrecht C, Haioun C, et al. (1993) Prognostic significance of received relative dose intensity in non-Hodgkin’s lymphoma patients: Application to LNH-87 protocol. Ann Oncol 4:651–656

    PubMed  CAS  Google Scholar 

  18. Lyman GH, Morrison VA, Dale DC, et al. (2003) Risk of febrile neutropenia among patients with intermediate-grade non-Hodgkin’s lymphoma receiving CHOP chemotherapy. Leuk Lymphoma 44:2069–2076

    Article  PubMed  CAS  Google Scholar 

  19. Lyman GH, Dale DC, Friedberg J, Crawford J, Fisher RI (2004) Incidence and predictors of low chemotherapy dose-intensity in aggressive non-Hodgkin’s lymphoma: a nationwide study. J Clin Oncol 22:4302–4311

    Article  PubMed  CAS  Google Scholar 

  20. Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer 47:207–214

    Article  PubMed  CAS  Google Scholar 

  21. Moore TD, Patel T, Segal ML, et al. (2003) A single pegfilgrastim dose per cycle supports dose-dense (q14d) CHOP-R in patients with non-Hodgkin’s lymphoma. Blood 102:abstract 2365

    Google Scholar 

  22. National Cancer Institute (2003) Small Cell Lung Cancer Treatment, vol 2004. US National Institutes of Health, Washington, DC

    Google Scholar 

  23. Noda K, Nishiwaki Y, Kawahara M, et al. (2002) Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med 346:85–91

    Article  PubMed  CAS  Google Scholar 

  24. Pfreundschuh M, Truemper L, Kloess M, et al. (2004) 2-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood 104:634–641

    Article  PubMed  CAS  Google Scholar 

  25. Steward WP, von Pawel J, Gatzemeier U, et al. (1998) Effects of granulocyte–macrophage colony-stimulating factor and dose intensification of V-ICE chemotherapy in small-cell lung cancer: a prospective randomized study of 300 patients. J Clin Oncol 16:642–650

    PubMed  CAS  Google Scholar 

  26. Thatcher N, Anderson H, Bleehen NM, et al. (1995) The feasibility of using glycosylated recombinant human granulocyte colony-stimulating factor (G-CSF) to increase the planned dose intensity of doxorubicin, cyclophosphamide and etoposide (ACE) in the treatment of small cell lung cancer. Medical Research Council Lung Cancer Working Party. Eur J Cancer 31A:152–156

    Article  PubMed  CAS  Google Scholar 

  27. Thatcher N, Clark PI, Smith DB, et al. (1995) Increasing and planned dose intensity of doxorubicin, cyclophosphamide and etoposide (ACE) by adding recombinant human methionyl granulocyte colony-stimulating factor (G-CSF; filgrastim) in the treatment of small cell lung cancer (SCLC). Medical Research Council Lung Cancer Working Party. Clin Oncol (R Coll Radiol) 7:293–299

    CAS  Google Scholar 

  28. Thatcher N, Girling DJ, Hopwood P, et al. (2000) Improving survival without reducing quality of life in small-cell lung cancer patients by increasing the dose-intensity of chemotherapy with granulocyte colony-stimulating factor support: results of a British Medical Research Council Multicenter Randomized Trial. Medical Research Council Lung Cancer Working Party. J Clin Oncol 18:395–404

    PubMed  CAS  Google Scholar 

  29. Therasse P, Arbuck SG, Eisenhauer EA, et al. (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216

    Article  PubMed  CAS  Google Scholar 

  30. Trillet-Lenoir V, Green J, Manegold C, et al. (1993) Recombinant granulocyte colony stimulating factor reduces the infectious complications of cytotoxic chemotherapy. Eur J Cancer 29A:319–324

    Article  PubMed  CAS  Google Scholar 

  31. Vose JM, Crump M, Lazarus H, et al. (2003) Randomized, multicenter, open-label study of pegfilgrastim compared with daily filgrastim after chemotherapy for lymphoma. J Clin Oncol 21:514–519

    Article  PubMed  CAS  Google Scholar 

  32. Woll PJ, Hodgetts J, Lomax L et al. (1995) Can cytotoxic dose-intensity be increased by using granulocyte colony-stimulating factor? A randomized controlled trial of lenograstim in small-cell lung cancer. J Clin Oncol 13:652–659

    PubMed  CAS  Google Scholar 

  33. Younes A, Fayad L, Romaguera J, et al. (2003) Single administration of a fixed dose pegfilgrastim (Neulasta) in inducing neutrophil count recovery after 170 consecutive doses of ABVD chemotherapy in patients with Hodgkin lymphoma: safety of pegfilgrastim with q14-day chemotherapy regimens. Blood 102:637a

    Google Scholar 

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Acknowledgments

The authors thank their coinvestigators and study nurses, particularly, Wilma Minar, RN, Dr. Christine Gomar–Höss, and Dr. Michael Shuhmacher. They also acknowledge the site and study management assistance of Thomas Horak and Felicity Norman, and the medical writing assistance of Joan O’Byrne and Sue Hudson

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Correspondence to R. Pirker MD.

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Pirker, R., Ulsperger, E., Messner, J. et al. Achieving Full-Dose, On-Schedule Administration of ACE Chemotherapy Every 14 Days for the Treatment of Patients with Extensive Small-Cell Lung Cancer. Lung 184, 279–285 (2006). https://doi.org/10.1007/s00408-005-2594-8

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  • DOI: https://doi.org/10.1007/s00408-005-2594-8

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