PMID- 8855989
OWN - NLM
STAT- MEDLINE
DCOM- 19961101
LR  - 20190515
IS  - 0007-0920 (Print)
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Linking)
VI  - 74
IP  - 7
DP  - 1996 Oct
TI  - 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.
PG  - 1141-7
AB  - 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.
FAU - Ardizzoni, A
AU  - Ardizzoni A
AD  - Division of Medical Oncology I, Istituto Nazionale per la Ricerca sul Cancro, 
      Genoa, Italy.
FAU - Pennucci, M C
AU  - Pennucci MC
FAU - Danova, M
AU  - Danova M
FAU - Viscoli, C
AU  - Viscoli C
FAU - Mariani, G L
AU  - Mariani GL
FAU - Giorgi, G
AU  - Giorgi G
FAU - Venturini, M
AU  - Venturini M
FAU - Mereu, C
AU  - Mereu C
FAU - Scolaro, T
AU  - Scolaro T
FAU - Rosso, R
AU  - Rosso R
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Journal Article
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 143011-72-7 (Granulocyte Colony-Stimulating Factor)
RN  - 6PLQ3CP4P3 (Etoposide)
RN  - 80168379AG (Doxorubicin)
RN  - 8N3DW7272P (Cyclophosphamide)
SB  - IM
MH  - *Antibiotic Prophylaxis
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage
MH  - Carcinoma, Small Cell/*drug therapy
MH  - Cyclophosphamide/administration & dosage
MH  - Doxorubicin/administration & dosage
MH  - Drug Administration Schedule
MH  - Etoposide/administration & dosage
MH  - Granulocyte Colony-Stimulating Factor/*administration & dosage
MH  - Humans
MH  - Lung Neoplasms/*drug therapy
MH  - Survival Analysis
MH  - Treatment Outcome
PMC - PMC2077108
EDAT- 1996/10/01 00:00
MHDA- 1996/10/01 00:01
CRDT- 1996/10/01 00:00
PHST- 1996/10/01 00:00 [pubmed]
PHST- 1996/10/01 00:01 [medline]
PHST- 1996/10/01 00:00 [entrez]
AID - 10.1038/bjc.1996.504 [doi]
PST - ppublish
SO  - Br J Cancer. 1996 Oct;74(7):1141-7. doi: 10.1038/bjc.1996.504.