Myeloprotective Effect of Early Primary Granulocyte-Colony Stimulating Factor during Six Courses of Intensified 5-Fluorouracil,Epirubicin and Cyclophosphamide (120FEC) Chemotherapy for Advanced Breast Cancer

Ardizzoni A. , Venturini M. , Sertoli M.R. , Giannessi P.G. , Brema F. , Danova M. , Testore F. , Mariani G.L. , Pennucci M.C. , Queirolo P. , Silvestro S. , Bruzzi P. , Lionetto R. , Latini F. , Rosso R. : Granulocyte-macrophage colony-stimulating factor (GM-CSF) allows acceleration and dose intensity increase of CEF chemotherapy: a randomized study in patients with advanced breast cancer. Br. J. Cancer, 69: 385–391, 1994.

Armitage P. , Berry G. : Statistical methods in medical research, 3rd Ed., Blackwell Science Publ., Oxford, 1994.

Bastholt L. , Dalmark M. , Gjedde S.B. , Pfeiffer P. , Pedersen D. , Sandberg E. , Kiaer M. , Mouridsen H.T. , Rose C. , Nielsen O.S. , Jakobsen P. , Bentzen S.M. : Dose-response relationship of epirubicin in the treatment of postmenopausal patients with metastatic breast cancer: a randomized study of epirubicin in four different dose levels performed by the Danish Breast Cancer Cooperative Group. J. Clin. Oncol., 14: 1146–1155, 1996.

Bissett D. , Jodrell D. , Harnett A.N. , Habeshaw T. , Kaye S.B. , Evans D. , Williams M. , Canney P.A. : Phase I study of accelerated FEC with granulocyte colony-stimulating factor (Lenograstim) support. Br. J. Cancer, 71: 1279–1282, 1995.

Blomquist C. , Elomaa I. , Rissanen P. , Hietanen P. , Nevasaari K. , Helle L. : Influence of treatment schedule on toxicity and efficacy of cyclophosphamide, epirubicin and fluorouracil in metastatic breast cancer: a randomized trial comparing weekly and every-4-week administration. J. Clin. Oncol., 11: 467–473, 1993.

Bronchud M.H. , Howell A. , Crowther D. , Hopwood P. , Souza L. , Dexter T.M. : The use of G-CSF to increase the intensity of treatment with doxorubicin in patients with advanced breast cancer. Br. J. Cancer, 60: 121–125, 1989.

Brufman G. , Colajori E. , Ghilezan N. , Lassus M. , Martoni A. , Perevodchikova N. , Tosello C. , Viaro D. , Zielinski C. : Epirubicin High Dose (HEPI 010) Study Group. Doubling epirubicin dose intensity (100 mg/sqm versus 50 mg/sqm) in the FEC regimen significantly increases response rates. An international randomised phase III study in metastatic breast cancer. Ann. Oncol., 8: 155–162, 1997.

Carmo-Pereira J. , Oliveira-Costa F. , Henriques E. , Godinho F. , Cantinho-Lopes M.G. , Sales-Luis A. , Rubens R.D. : A comparison of two doses of adriamycin in the primary chemotherapy of disseminated breast cancer. Br. J. Cancer, 56: 417–473, 1987.

Cascinu S. , Fedeli A. , Del Ferro E. , Luzi Fedele S. , Catalano G. : Recombinant human erythropoietin treatment in cisplatin associated anemia: a randomized, double-blind trial with placebo. J. Clin. Oncol., 12: 1058–1062, 1994.

Colajori E. , Tosello C. , Pannuti F. : Randomized multinational trial comparing epirubicin (EPI) 50 mg/mq vs 100 mg/mq in combination with 5-fluorouracil (5FU) and cyclophosphamide (CTX) as front line treatment of metastatic breast cancer (MBC). Abstr. ESMO Congress, Lisbon, 21 November 1994. Ann. Oncol., 5 (suppl 8): 26 (abstract 126), 1994.

Crawford J. , Ozer H. , Stoller R. , Johnson D. , Lyman G. , Tab-bara I. , Kris M. , Grous J. , Picozzi V. , Rausch G. , Smith R. , Gradishar W. , Yahanda A. , Vincent M. , Stewart M. , Glaspy J. : 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, 1991.

Danova M. , Rosti V. , Mazzini G. , De Renzis M.R. , Locatelli F. , Cazzola M. , Riccardi A. , Ascari E. : Cell kinetics of CD34-positive hematopoietic cells following chemotherapy plus colony-stimulating factors in advanced breast cancer. Int. J. Cancer, 63: 646–651, 1995.

Danova M. , Mazzini G. , Alberici R. , Lucotti C. , Palmeri S. , Fincato G. , Cazzola M. , Riccardi A. , Ascari E. : Sequential administration of interleukin-3 and granulocyte-macrophage colony-stimulating factor following intensified, accelerated CEE (cyclophosphamide, epirubicin, etoposide) chemotherapy: cytokinetic effects on bone marrow hematopoietic progenitors. Int. J. Oncol., 9: 971–976, 1996.

Danova M. , Comolli G. , Mazzini G. , Riccardi A. , Ascari E. : Cell cycle analysis and detection of apoptosis in human bone marrow and blood-derived CD34+/CD38+ cells following paclitaxel ± G-CSF in cancer patients. Proc. ASCO, 16: 114a (abstract 400), 1997.

Del Mastro L. , Venturini M. , Garrone O. , Sertoli M.R. , Pas-quetti W. , Pastorini S. , Lionetto R. , Rosso R. : Erythropoietin in the prevention of chemotherapy induced anemia: results from a prospective trial in early breast cancer patients. Proc. ASCO, 14: 256 (abstract 697), 1995.

De Wit R. , Verweij J. , Bontenbal M. , Kruit W.H.J. , Seynaeve C. , Schmitz P.I.M. , Stoter G. : Adverse effect of bone marrow protection of prechemotherapy granulocyte colony-stimulating factor support. J. Natl. Cancer Inst., 88: 1393–1398, 1995.

Ferguson J.E. , Dodwell D.J. , Seymour A.M. , Richards M.A. , Howell A. : High dose, dose-intensive chemotherapy with doxorubicin for the treatment of advanced breast cancer. Br. J. Cancer, 67: 825–829, 1993.

Focan C. , Andrien J.M. , Closon M. Th. , Dicato M. , Driess-chaert P. , Focan-Henrard D. , Lemaire M. , Labelle J.P. , Logree I. , Ries F. : Dose-response relationship of epirubicin-based first-line chemotherapy for advanced breast cancer: a prospective randomized trial. J. Clin. Oncol., 11: 1253–1263, 1993.

Fountzilas G. , Skarlos D. , Giannakakis T. , Athanasiades A. , Bafaloukos D. , Kalogra-Fountzila A. , Bamia C. , Pavlidis N. , Kosmidis P. : Intensive chemotherapy with high dose epirubicin every 2 weeks and prophylactic administration of filgrastim in advanced breast cancer. Eur. J. Cancer, 30: 965–969, 1994.

French Epirubicin Study Group: A prospective randomized trial comparing epirubicin monochemotherapy to two fluorouracil, cyclophosphamide and epirubicin regimens differing in epirubicin dose in advanced breast cancer patients. J. Clin. Oncol., 9: 305–312, 1991.

Habeshaw T. , Paul J. , Jones R. , Stallard S. , Steward M. , Kaye S.B. , Soukop M. , Symonds R.P. , Reed N.S. , Rakin E.M. : Epirubicin at two dose levels with prednisolone as treatment for advanced breast cancer: the results of a randomized trial. J. Clin. Oncol., 9: 295–304, 1991.

Henderson I.C. , Hayes D.F. , Gelman R. : Dose response in the treatment of breast cancer: a critical review. J. Clin. Oncol., 6: 1501–1515, 1988.

Hortobagyi G.N. , Bodey G.B. , Buzdar A.U. , Frye D. , Legha S.S. , Malik R. , Smith T.L. , Blumenschein G.R. , Yap H. , Rodriguez V. : Evaluation of high-dose versus standard FAC chemotherapy for advanced breast cancer in protected environment units: a prospective randomized study. J. Clin. Oncol., 5: 354–364, 1987.

Hryniuk W. , Bush H. : The importance of dose-intensity in chemotherapy of metastatic breast cancer. J. Clin. Oncol., 2: 1281–1288, 1984.

Lalisang R.I. , Wils J.A. , Nortier H.W. , Burghouts J.Th. , Hup-perets P.S. , Erdkamp E.L. , Schouten H.C. , Blijham G.H. : Comparative study of dose-escalation versus interval reduction to obtain dose-intensification of epirubicin and cyclophosphamide with granulocyte colony-stimulating factor in advanced breast cancer. J. Clin. Oncol., 15: 1367–1376, 1997.

Marschner N. , Kreienberg R. , Souchon R. , Rath U. , Eggeling B. , Voigtmann R. , Ruffert K. , Schutte M. , Ammon A. , Kesz-tyus T. , Kaplan E. , Nagel G. : Evaluation of the importance and relevance of dose intensity using epirubicin and cyclophosphamide in metastatic breast cancer: interim analysis of a prospective randomized trial. Sem. Oncol., 21(suppl. 1): 10–16, 1994.

Ogawa M. : High dose epirubicin studies on metastatic breast cancer in Japan. In: Satellite Symposium ESMO Congress: Intensive therapy for solid tumors: epirubicin, p. 16 (abstract), Lisbon, 21 November, 1994.

Osborne C.K. , Sunderland M.C. , Neidhart J.A. , Ravdin P.M. , Abeloff M.D. : Failure of GM-CSF to permit dose-escalation in an every other week dose-intensive regimen for advanced breast cancer. Ann. Oncol., 5: 43–47, 1994.

O'Shaughnessy J.A. , Denicoff A.M. , Venzon D.J. , Danforth D. , Pierce L.J. , Frame J.N. , Bastian A. , Ghosh B. , Goldspiel L.J. , Miller L. , Dorr F.A. , Keegan P. , Ben-Baruch N. , Mrose H. , Noone M. , Cowan K.H. : A dose intensity study of FLAC (5 fluorouracil, leucovorin, doxorubicin, cyclophosphamide) chemotherapy and Escherichia coli derived granulocyte-monocyte-colony stimulating factor (GM-CSF) in advanced breast cancer patients. Ann. Oncol., 5: 709–716, 1994.

Paccagnella A. , Favaretto A. , Riccardi A. , Danova M. , Ghiotto C. , Giordano M. , Pappagallo G. , Comis S. , Panozzo M. , Chieco-Bianchi L. , Fiorentino M.V. : GM-CSF increases dose intensity of chemotherapy in small cell lung cancer. Relationship between clinical results, peripheral blood cell modifications and bone marrow kinetics. Cancer, 72: 697–706, 1993.

Penella J.W. , Hodgetts J. , Lomax L. , Bildet F. , Cour-Chaber-naud V. , Thatcher N. : 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, 1995.

Riccardi A. , Danova M. , Paccagnella A. , Giordano M. , Fara-vetto A. , Panozzo M. , Ghiotto C. , Comis S. , Fiorentino M. , Chieco-Bianchi L. , Ascari E. : Bone marrow myeloid cell kinetics during treatment of small cell carcinoma of the lung with chemotherapy not associated and associated with granulocyte-macrophage colony stimulating factor. Ann. Hematol., 66: 185–193, 1993.

Riccardi A. , Giordano M. , Brugnatelli S. , Ucci G. , Danova M. , Epifani C. , Ascari E. : Different doses of epirubicin associated with fixed doses of cyclophosphamide and 5-fluorouracil: a randomized study in advanced breast cancer. Eur. J. Cancer, 31: 1549–1551, 1995.

Scinto A.F. , Cercato M.C. , Botti C. , Tonachella R. , Ferraresi V. , Del Bianco S. , Sacchi D. , Cognetti F. : Phase II trial of high-dose epirubicin and cyclophosphamide in advanced breast cancer. Eur. J. Cancer, 30: 1285–1288, 1994.

STATISTICA for Windows (Computer program manual). StatSoft Inc, Tulsa, 1997.

Tjan-Heijnen V.C.G. , Biesma B. , Festen J. , Splinter T.A.W. , Cox A. , Wagener D.J.T. , Postmus P.E. : Enhanced myelotoxicity due to granulocyte colony-stimulating factor administration until 48 hours before the next chemotherapy course. J. Clin. Oncol., 16: 2708–2714, 1996.

Vadhan-Raj S. , Broxmeyer H.E. , Hittelman W.N. , Papadopoulos N.E. , Chawla S.P. , Fenoglio C. , Cooper S. , Buescher E.S. , Frenck R.W. , Holian A. , Perkins R.C. , Scheule R.K. , Gutter-man J.U. , Salem P. , Benjamin R.S. : Abrogating chemotherapy-induced myelosuppression by recombinant granulocyte-macrophage colony-stimulating factor in patients with sarcoma: protection at the progenitor cell level. J. Clin. Oncol., 10; 1266–1277, 1992.

Van Hoef H.E.H.M. , Baumann I. , Lange C. , Luft T. , De Wyn-ter E.A. , Ranson M. , Morgenstern G.R. , Yvers A. , Dexter T.M. , Testa N.G. , Howell A. : Dose-escalating induction chemotherapy supported by lenograstim preceding high-dose consolidation chemotherapy for advanced breast cancer. Selection of the most acceptable regimen to induce maximal tumor response and investigation of the optimal time to collect peripheral blood progenitor cells for haematological rescue after high-dose consolidation chemotherapy. Ann. Oncol., 5: 217–224, 1994.

Venturini M. , Del Mastro L. , Testore F. , Garrone O. , Lanfranco C. , Latini F. , Sertoli M.R. , Lionetto R. , Queirolo P. , Ardizzoni A. , Rosso R. : Erythropoietin and granulocyte-macrophage colony-stimulating factor allow acceleration and dose escalation of cyclophoshamide/epidoxorubicin/5-chemotherapy: a dose-finding study in patients with advanced breast cancer. Cancer Chemother. Pharmacol., 38: 487–494, 1996.