Prophylactic granulocyte colony-stimulating factor allows escalation of chemotherapeutic dose intensity in advanced epithelial ovarian cancer.

Author(s): Fanning J, Hilgers RD

Affiliation(s): Division of Gynecologic Oncology, Medical College of Ohio, Toledo 43699-0008, USA.

Publication date & source: 1996-12, Gynecol Oncol., 63(3):323-7.

Publication type: Clinical Trial; Clinical Trial, Phase II

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. CONCLUSION: 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.