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 P hase III evaluation of the efficacy of dose intensification in advance d ovarian cancer, we performed a Phase II trial of dose intensified ci splatin, etoposide, and ifosfamide with granulocyte colony-stimulating factor (G-CSF). Methods: Thirty patients with primary, FIGO Stage 3 o r 4, epithelial ovarian cancer underwent intensified cytoreduction fol lowed by cisplatin 105 mg/m2, etoposide 300 mg/m(2) and ifosfamide/mes na 3 g/m(2), q 28 daysx6 cycles with G-CSF 5 mu g/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 success ful in resecting all gross tumor in 24 patients (80%). At the original dose of cisplatin, etoposide, and ifosfamide without G-CSF, 55% of cy cles resulted in neutropenia and 38% in thrombocytopenia (dose intensi ty=0.8). With the addition of G-CSF, neutropenia developed in 5% of cy cles and thrombocytopenia in 38%. At a 20% escalation of etoposide and ifosfamide, neutropenia developed in 17% of cycles and thrombocytopen ia in 50% (dose intensity=1.2). At a 40% escalation of etoposide and i fosfamide, neutropenia developed in 33% of cycles and thrombocytopenia in 83%, which was dose limiting. The remaining 18 patients were treat ed 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 s urvival was 3.0 years. Conclusion: In 30 women with primary advanced o varian cancer, G-CSF allowed a 50% dose escalation of etoposide and if osfamide from 0.8 to 1.2 dose intensity. The maximum tolerated dose of this regimen is cisplatin 105 mg/m(2), etoposide 360 mg/m(2), and ifo sfamide 3.6 g/m(2) with G-CSF. (C) 1996 Academic Press, Inc.