Skip to main content
Top
Published in: Lung 5/2006

01-10-2006

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

Authors: R. Pirker, MD, E. Ulsperger, J. Messner, K. Aigner, B. Forstner, P. Bacon, V. Easton, T. Skacel

Published in: Lung | Issue 5/2006

Login to get access

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.
Literature
1.
go back to reference 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 20:3947–3955PubMedCrossRef 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 20:3947–3955PubMedCrossRef
2.
go back to reference 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 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
3.
go back to reference 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 332:901–906PubMedCrossRef 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 332:901–906PubMedCrossRef
4.
go back to reference 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 90:1205–1211PubMedCrossRef 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 90:1205–1211PubMedCrossRef
5.
go back to reference 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 21:1431–1439PubMedCrossRef 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 21:1431–1439PubMedCrossRef
6.
go back to reference 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 325:164–170PubMedCrossRef 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 325:164–170PubMedCrossRef
7.
go back to reference 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 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
8.
go back to reference Epelbaum R, Faraggi D, Ben-Arie Y, et al. (1990) Survival of diffuse large cell lymphoma: a muitivariate analysis including dose intensity variables. Cancer 66:1124–1129PubMedCrossRef Epelbaum R, Faraggi D, Ben-Arie Y, et al. (1990) Survival of diffuse large cell lymphoma: a muitivariate analysis including dose intensity variables. Cancer 66:1124–1129PubMedCrossRef
9.
go back to reference 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 14:29–35PubMedCrossRef 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 14:29–35PubMedCrossRef
10.
go back to reference 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 44:1503–1508PubMedCrossRef 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 44:1503–1508PubMedCrossRef
11.
go back to reference 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 13:903–909PubMedCrossRef 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 13:903–909PubMedCrossRef
12.
go back to reference Ihde DC (1995) Small cell lung cancer. State-of-the-art therapy 1994. Chest 107:243S–248SPubMed Ihde DC (1995) Small cell lung cancer. State-of-the-art therapy 1994. Chest 107:243S–248SPubMed
13.
go back to reference 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 12:2022–2034PubMed 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 12:2022–2034PubMed
14.
go back to reference 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 5:1731–1738PubMed 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 5:1731–1738PubMed
15.
go back to reference 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 18:2522–2528PubMed 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 18:2522–2528PubMed
16.
go back to reference 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 8:963–977PubMed 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 8:963–977PubMed
17.
go back to reference 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 4:651–656PubMed 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 4:651–656PubMed
18.
go back to reference 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 44:2069–2076PubMedCrossRef 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 44:2069–2076PubMedCrossRef
19.
go back to reference 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 22:4302–4311PubMedCrossRef 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 22:4302–4311PubMedCrossRef
20.
go back to reference Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer 47:207–214PubMedCrossRef Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer 47:207–214PubMedCrossRef
21.
go back to reference 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 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
22.
go back to reference National Cancer Institute (2003) Small Cell Lung Cancer Treatment, vol 2004. US National Institutes of Health, Washington, DC National Cancer Institute (2003) Small Cell Lung Cancer Treatment, vol 2004. US National Institutes of Health, Washington, DC
23.
go back to reference 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 346:85–91PubMedCrossRef 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 346:85–91PubMedCrossRef
24.
go back to reference 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 104:634–641PubMedCrossRef 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 104:634–641PubMedCrossRef
25.
go back to reference 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 16:642–650PubMed 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 16:642–650PubMed
26.
go back to reference 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:152–156PubMedCrossRef 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:152–156PubMedCrossRef
27.
go back to reference 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 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
28.
go back to reference 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 18:395–404PubMed 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 18:395–404PubMed
29.
go back to reference 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 92:205–216PubMedCrossRef 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 92:205–216PubMedCrossRef
30.
go back to reference 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:319–324PubMedCrossRef 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:319–324PubMedCrossRef
31.
go back to reference 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 21:514–519PubMedCrossRef 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 21:514–519PubMedCrossRef
32.
go back to reference 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 13:652–659PubMed 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 13:652–659PubMed
33.
go back to reference 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 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
Metadata
Title
Achieving Full-Dose, On-Schedule Administration of ACE Chemotherapy Every 14 Days for the Treatment of Patients with Extensive Small-Cell Lung Cancer
Authors
R. Pirker, MD
E. Ulsperger
J. Messner
K. Aigner
B. Forstner
P. Bacon
V. Easton
T. Skacel
Publication date
01-10-2006
Publisher
Springer-Verlag
Published in
Lung / Issue 5/2006
Print ISSN: 0341-2040
Electronic ISSN: 1432-1750
DOI
https://doi.org/10.1007/s00408-005-2594-8

Other articles of this Issue 5/2006

Lung 5/2006 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine