Reduction by Granulocyte Colony-Stimulating Factor of Fever and Neutropenia Induced by Chemotherapy in Patients with Small-Cell Lung Cancer
- Study type
- Clinical trial
- Study name
- Crawford 1991
- Phase
- Phase 3
- Design
- Multicentre, randomised, double-blind, placebo-controlled trial
- Sample size
- 211 patients randomised (safety in 207 and efficacy in 199 evaluable patients)
- Source
- N Engl J Med · 1991
In plain words
Chemotherapy can lower the number of infection-fighting white blood cells (neutrophils) and raise the risk of fever and infection. In this study, a daily injection of filgrastim (Neupogen) after chemotherapy cut the chance of fever with low white blood cells roughly in half and reduced days in hospital and use of antibiotics through a vein. The most common side effect was mild to moderate bone pain.
Key results
Treatment arms and regimens
Up to 6 cycles of 21-day IV chemotherapy: cyclophosphamide and doxorubicin on day 1 + etoposide on days 1, 2 and 3 (chemotherapy doses could not be verified in the available sources), with filgrastim subcutaneously 230 µg/m² daily (equivalent to 4 to 8 µg/kg per day) from day 4 to day 17 of each cycle (maximum 14 days per cycle) — 99 efficacy-evaluable patients according to the FDA label.
The same chemotherapy (up to 6 cycles) with daily subcutaneous placebo from day 4 to 17 of each cycle (111 efficacy-evaluable patients according to the FDA label).
Source of the regimen details: Administration schedule (days 4 to 17 of each 21-day cycle, up to 6 cycles) from the abstract of the paper; filgrastim dose (230 µg/m², 4 to 8 µg/kg per day, maximum 14 days) and chemotherapy administration days from section 14.1 of the FDA label for Neupogen (DailyMed, July 2026 version). The chemotherapy doses could not be verified (full text not available).
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients with small-cell lung cancer (according to the FDA label: 72% extensive stage and 28% limited stage; median age 62 years) receiving up to 6 cycles of standard chemotherapy with cyclophosphamide, doxorubicin and etoposide.
Endpoints
Primary endpoint: incidence of infection as manifested by febrile neutropenia (absolute neutrophil count below 1.0 × 109/L and temperature ≥ 38.2 °C).
Other endpoints: duration and severity of grade 4 neutropenia, days of IV antibiotics, days in hospital and culture-confirmed infections.
Safety and side effects
Mild to moderate bone (marrow) pain occurred in 20% of patients receiving G-CSF; the drug was well tolerated.
Clinical significance and place in guidelines
This trial was the basis for FDA approval of filgrastim (Neupogen) in 1991 to reduce infection as manifested by febrile neutropenia in patients receiving myelosuppressive chemotherapy; the FDA label calls this study "Study 1" and reports an incidence of febrile neutropenia of 40% versus 76%. The ASCO guideline recommends prophylactic use of growth factors when the risk of febrile neutropenia is about 20% or higher.
Limitations
The study was conducted only in small-cell lung cancer with a single chemotherapy regimen and was not designed to assess the effect on overall survival.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.