Phase I study of simultaneous dose escalation and schedule acceleration of cyclophosphamide-doxorubicin-etoposide using granulocyte colony-stimulating factor with or without antimicrobial prophylaxis in patients with small-cell lung cancer
| Autor: | Andrea Ardizzoni, R. Rosso, Marco Danova, G. Giorgi, M. Venturini, M. C. Pennucci, Carlo Mereu, T. Scolaro, G. L. Mariani, C. Viscoli |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Cancer Research
medicine.medical_specialty Lung Neoplasms Cyclophosphamide medicine.medical_treatment Gastroenterology Drug Administration Schedule Internal medicine Antineoplastic Combined Chemotherapy Protocols Granulocyte Colony-Stimulating Factor medicine Mucositis Humans Carcinoma Small Cell Antibiotic prophylaxis Etoposide Chemotherapy business.industry Antibiotic Prophylaxis medicine.disease Survival Analysis Granulocyte colony-stimulating factor Surgery Regimen Treatment Outcome Oncology Doxorubicin Chemoprophylaxis business Research Article medicine.drug |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/bjc.1996.504 |
| Popis: | A phase I study was designed to assess whether dose intensity of an 'accelerated' cyclophosphamide-doxorubicin-etoposide (CDE) regimen plus granulocyte colony-stimulating factor (G-CSF) could be increased further, in an outpatient setting, by escalating the dose of each single drug of the regimen. Patients with previously untreated small-cell lung cancer (SCLC) received escalating doses of cyclophosphamide (C) 1100-1300 mg m-2 intravenously (i.v.) on day 1, doxorubicin (D) 50-60 mg m-2 i.v. on day 1, etoposide (E) 110-130 mg m-2 i.v. on days 1, 2, 3 and every 14 days for at least three courses. Along with chemotherapy, G-CSF (filgastrim) 5 micrograms kg-1 from day 5 to day 11 was administered subcutaneously (s.c.) to all patients. Twenty-five patients were enrolled into the study. All patients at the first dose level (C 1100, D 50, E 110 x 3) completed three or more cycles at the dose and schedule planned by the protocol and no 'dose-limiting toxicity' (DLT) was seen. At the second dose level (C 1200, D 55, E 120 x 3) three out of five patients had a DLT consisting of 'granulocytopenic fever' (GCPF). Another six patients were treated at this dose level with the addition of ciprofloxacin 500 mg twice a day and only two patients had a DLT [one episode of documented oral candidiasis and one of 'fever of unknown origin' (FUO) with generalised mucositis]. Accrual of patients proceeded to the third dose level (C 1300, D 60, E 130 x 3) with the prophylactic use of ciprofloxacin. Four out of six patients experienced a DLT consisting of GCPF or documented non-bacterial infection. Accrual of patients at the third dose level was then resumed adding to ciprofloxacin anti-fungal prophylaxis (fluconazole 100 mg daily) and anti-viral prophylaxis (acyclovir 800 mg twice a day) from day 5 to 11. Out of five patients treated three experienced a DLT consisting of severe leucopenia and fever or infection. With a simultaneous dose escalation and schedule acceleration it is indeed possible to take maximum advantage of G-CSF activity and to increase CDE dose intensity by a factor 1.65-1.80 for a maximum of 3-4 courses. The role of antimicrobial prophylaxis in this setting deserves to be investigated further. |
| Databáze: | OpenAIRE |
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