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

A. Paccagnella, A. Favaretto, A. Riccardi, M. Danova, C. Ghiotto, M. Giordano, G. Pappagallo, S. Comis, M. Panozzo, L. Chieco-Bianchi, M. V. Fiorentino

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Abstract

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/m 2, etoposide 120 mg/m 2 x 3, and escalating epirubicin (5 mg/m 2) starting from 45 mg/m 2, every 3 weeks for six courses. Results. The maximum tolerated dose (MTD) was reached at epirubicin 60 mg/m 2. 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/m 2. 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/m 2. 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.

Original languageEnglish
Pages (from-to)697-706
Number of pages10
JournalCancer
Volume72
Issue number3
Publication statusPublished - 1993

Keywords

  • chemotherapy
  • dose escalation
  • dose intensity
  • GM-CSF
  • in vivo BrdU
  • labeling index
  • myeloid precursors
  • small cell lung cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Paccagnella, A., Favaretto, A., Riccardi, A., Danova, M., Ghiotto, C., Giordano, M., Pappagallo, G., Comis, S., Panozzo, M., Chieco-Bianchi, L., & 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(3), 697-706.