title: Accelerated cisplatin and high-dose epirubicin with G-CSF support in patients with relapsed non-small-cell lung cancer: feasibility and efficacy.
abstract: The purpose of this study is to determine whether it is feasible to administer high-dose epirubicin (135 mg m(-2)) combined with a fixed dose of cisplatin every 2 weeks with G-CSF support in patients with metastatic non-small-cell lung cancer (NSCLC). Subsequently, the efficacy of the recommended dose of this regimen was tested in a phase II study in patients with relapsed NSCLC. In the initial feasibility study at least 6 patients were entered at each of the 4 dose levels tested. A fixed dose of cisplatin 60 mg m(-2) was given. Epirubicin was administered at 120 mg m(-2) on dose level 1, 135 mg m(-2) on dose level 2 and 3 and 135 mg m(-2) on dose level 4. Patients treated at dose level 3 and 4 received G-CSF support on days 3-12. Cycles were repeated every 3 weeks on the first 3 dose levels and every 2 weeks on the fourth dose level. A total of 27 patients were then treated on dose level 4, which appeared to be feasible in the initial study. In the initial study, a total of 86 courses were administered. Haematological toxicity was the principal side effect. None of the patients encountered dose-limiting toxicity in the first course, which confirmed that epirubicin 135 mg m(-2) could be combined with cisplatin 60 mg m(-2) and accelerated by G-CSF support to a 14-day-schedule. In the subsequent phase II study with this schedule, 89 courses were administered. The relative dose intensity of cisplatin and epirubicin was 0.90 and 0.91, respectively. Myelosuppression was frequent with 70% and 63% of patients experiencing WHO grade III or IV leukocytopenia and thrombocytopenia, respectively. 6 cases of febrile neutropenia were observed, with 2 treatment-related deaths. Non-haematological toxicity consisted mainly of nausea and vomiting, which was grade III in 22% of patients. Renal toxicity grade I and II occurred in 37% and 4% of patients, respectively. 55% of these patients had received prior cisplatin-containing chemotherapy. On an intention-to-treat basis 9 partial responses were recorded in 27 patients (33%; 95% confidence interval, 15%-51%). Accelerated cisplatin and high-dose epirubicin with G-CSF support is a feasible and promising regimen in relapsed NSCLC. Myelosuppression limits the use of this regimen in the second-line setting to a selected group of patients with a good performance status. Since the activity of this regimen is encouraging, it is probably best studied in untreated patients.
authors.affiliation: Department of Pulmonary Diseases, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Huisman
authors.forename: B
authors.initials: B
authors.lastname: Biesma
authors.forename: P E
authors.initials: PE
authors.lastname: Postmus
authors.forename: G
authors.initials: G
authors.lastname: Giaccone
authors.forename: F M
authors.initials: FM
authors.lastname: Schramel
authors.forename: E F
authors.initials: EF
authors.lastname: Smit
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006402:Hematologic Diseases / Q000209:etiology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D002945:Cisplatin