Granulocyte-macrophage colony-stimulating factor increases dose intensity of chemotherapy in small cell lung cancer: Relationship between clinical results, peripheral blood cell modifications, and bone marrow kinetics
Article first published online: 28 JUN 2006
Copyright © 1993 American Cancer Society
Volume 72, Issue 3, pages 697–706, 1 August 1993
How to Cite
Paccagnella, A., Favaretto, A., Riccardi, A., Danova, M., Ghiotto, C., Giordano, M., Pappagallo, G., Comis, S., Panozzo, M., Chieco-Bianchi, L. and Fiorentino, M. V. (1993), Granulocyte-macrophage colony-stimulating factor 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. doi: 10.1002/1097-0142(19930801)72:3<697::AID-CNCR2820720312>3.0.CO;2-U
- Issue published online: 28 JUN 2006
- Article first published online: 28 JUN 2006
- Manuscript Accepted: 15 MAR 1993
- Associazione Italiana per la Ricerca sul Cancro, Milano
- Lega Italiana per la Lotta contro i Tumori, Padova
- Consiglio Nazionale delle Ricerche, Roma
- Progetto Finalizzato Applicazioni Cliniche della Ricerca Oncologica. Grant Number: 88.00841.44
- IRCCS Policlinico S. Matteo Pavia
- small cell lung cancer;
- dose escalation;
- dose intensity;
- in vivo BrdU;
- myeloid precursors;
- labeling index
Background. Until now, no dose-response correlation has been clearly defined in small cell lung cancer (SCLC).
Methods. Forty-one consecutive patients with SCLC entered this study, 21 (limited [L]/extensive [E] = 10/11) patients (group A) received cisplatin 60 mg/m2, etoposide 120 mg/m2 X 3, and escalating epirubicin (5 mg/m2) starting from 45 mg/m2, every 3 weeks for six courses.
Results. The maximum tolerated dose (MTD) was reached at epirubicin 60 mg/m2. In 15 (L/E = 9/6) patients (group B), who were submitted to the same combination plus granulocyte-macrophage colony-stimulating factor (GM-CSF) 10 μg/kg on days 4 to 14, the MTD was reached at the epirubicin dose of 70 mg/m2. In five (L/E = 4/1) patients (group C) treated as in group B, but with a GM-CSF priming from day -17 to -7 before the first cycle, the MTD was again at 70 mg/m2. Group A patients received 73% of the planned cycles; groups B and C, 86% (P < 0.015). Twenty-five percent of group A cycles versus 6% of groups B and C were delayed (P = 0.0018). The chemotherapy dose was reduced in 15% versus 1.5% of cycles (P = 0.0072). A significant difference was observed in the delivered dose intensity (DI) and in the relative DI with an increase of 29% for cisplatin and etoposide (P < 0.0005; P = 0.0017) and of 63% for epirubicin (P < 0.0000). In group A, the response rate was 72% (24% complete response [CR]), and in groups B and C, 95% (40% CR). Bone marrow myeloid precursor (BMMP) proliferative activity was determined in 21 patients after in vivo bromodeoxyuridine infusion. In GM-CSF-treated patients the production rate evaluated before the starting of the second, fourth, and fifth cycle was significantly higher than the corresponding value of the first cycle.
Conclusions. GM-CSF induces a significant increase of dose intensity by a long-lasting and cumulative enhancement of BMMP proliferation.