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 micrograms/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.