Prophylactic granulocyte colony-stimulating factor allows escalation of chemotherapeutic dose intensity in advanced epithelial ovarian cancer.
BACKGROUND
In an effort to discover an effective regimen for use in Phase III evaluation of the efficacy of dose intensification in advanced ovarian cancer, we performed a Phase II trial of dose intensified cisplatin, etoposide, and ifosfamide with granulocyte colony-stimulating factor (G-CSF).


METHODS
Thirty patients with primary, FiGO Stage 3 or 4, epithelial ovarian cancer underwent intensified cytoreduction followed by cisplatin 105 mg/m2, etoposide 300 mg/m2 and ifosfamide/mesna 3 g/m2, q 28 days x 6 cycles with G-CSF 5 microg/kg q day for 7 days. The dose of etoposide and ifosfamide was escalated 20% in cohorts of three patients.


RESULTS
Intensified cytoreductive surgery was successful in resecting all gross tumor in 24 patients (80%). At the original dose of cisplatin, etoposide, and ifosfamide without G-CSF, 55% of cycles resulted in neutropenia and 38% in thrombocytopenia (dose intensity = 0.8). With the addition of G-CSF, neutropenia developed in 5% of cycles and thrombocytopenia in 38%. At a 20% escalation of etoposide and ifosfamide, neutropenia developed in 17% of cycles and thrombocytopenia in 50% (dose intensity = 1.2). At a 40% escalation of etoposide and ifosfamide, neutropenia developed in 33% of cycles and thrombocytopenia in 83%, which was dose limiting. The remaining 18 patients were treated at a 20% escalation and neutropenia developed in 14% of cycles and thrombocytopenia in 36%. CA125 response was 73%. At a 4.1-year median follow-up, median progression-free survival was 2.6 years and median survival was 3.0 years.


CONCLUSIONS
In 30 women with primary advanced ovarian cancer, G-CSF allowed a 50% dose escalation of etoposide and ifosfamide from 0.8 to 1.2 dose intensity. The maximum tolerated dose of this regimen is cisplatin 105 mg/m2, etoposide 360 mg/m2, and ifosfamide 3.6 g/m2 with G-CSF.
Fanning
J
J
Division of Gynecologic Oncology, Medical College of Ohio, Toledo 43699-0008, USA.
Hilgers
R D
RD
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control
D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D002945:Cisplatin; D007069:Ifosfamide