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.
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.
Paccagnella
A
A
Division of Medical Oncology, General Hospital, Padova, Italy.
Favaretto
A
A
Riccardi
A
A
Danova
M
M
Ghiotto
C
C
Giordano
M
M
Pappagallo
G
G
Comis
S
S
Panozzo
M
M
Chieco-Bianchi
L
L
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000097:blood / Q000188:drug therapy*; D002452:Cell Count / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D015251:Epirubicin; D005047:Etoposide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002945:Cisplatin