Phase I study of chemotherapy with carboplatin, epirubicin, and escalating dose of VP-16 with G-CSF support in extensive small cell lung cancer.
In attempt to develop a new chemotherapeutic regimen including carboplatin (CBDCA), epirubicin (EPI), and VP-16 in extensive small cell lung cancer, with a higher dose intensity compared with previous experience of our group, we determined the maximum tolerated dose (MTD) of VP-16 when administered in association with CBDCA (300 mg/ m2, i.v., day 1) and EPI (75 mg/m2, i.v., day 1), recycling chemotherapy every 3 weeks, with the support of granulocyte-colony-stimulating factor (G-CSF). A total of 15 patients received three dose levels of VP-16 (mg/m2, i.v., daily on days 1-3): 100 (three patients), 120 (six), and 140 (six). G-CSF was administered subcutaneously at the dose of 5 micrograms/kg/day on days 6-15 of each chemotherapy course. The MTD was established at 140 mg/m2 and myelotoxicity, grade 4 neutropenia with death for sepsis in one case and grade 3 thrombocytopenia in three cases, was dose limiting. The recommended dose of VP-16 for a phase II study is 140 mg/m2.
Gridelli
C
C
Division of Medical Oncology, Faculty of Medicine, Federico II University, Naples, Italy.
D'Aprile
M
M
Palmeri
S
S
Curcio
C
C
Rossi
A
A
Gebbia
V
V
Veltri
E
E
Pepe
R
R
Pistillucci
G
G
Bianco
A R
AR
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D002423:Cause of Death; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D015251:Epirubicin / Q000008:administration & dosage* / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control; D018805:Sepsis / Q000209:etiology; D013921:Thrombocytopenia / Q000139:chemically induced
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D005047:Etoposide; D016190:Carboplatin