A multicenter randomized phase II trial of granulocyte-colony stimulating factor-supported, platinum-based chemotherapy with flexible midcycle cisplatin administration in patients with advanced ovarian carcinoma

BACKGROUND. The purpose of this study was to analyze whether the addition of granulocyte-colony stimulating factor (G-CSF) to platinum-based combination chemotherapy could increase platinum dose intensity and response rates and decrease hematologic toxicity in patients with advanced epithelial ovarian carcinoma. METHODS. Patients with untreated advanced ovarian carcinoma (International Federation of Gynecology and Obstetrics [FIGO] Stage IIC-IV) were treated after maximum debulking surgery with cyclophosphamide, 750 mg/m², and carboplatin, 350 mg/m², on Day 1 plus cisplatin, 75 mg/m², on Day 14 when clinically indicated (adequate bone marrow and renal function). Patients were randomized to receive chemotherapy alone (Arm A) or chemotherapy supported with G-CSF (5 μg/kg subcutaneously on Days 2-13; Arm B). RESULTS. Between November 1993 and April 1995, 80 patients were included. Seventy-eight patients were evaluable for dose intensity calculations. Both groups were well matched with regard to age, Eastern Cooperative Oncology Group performance status, histopathologic subtype, tumor grade, FIGO stage, and residual tumor after surgery. The dose intensities calculated in mg/m²/week for cyclophosphamide and carboplatin were similar in both groups; however, the dose intensity of cisplatin was higher in Arm B (5.7 mg/m² vs. 10.3 mg/m²). The occurrence of Common Toxicity Criteria Grade 3-4 neutropenia was less common in the G-CSF arm (55% vs. 7.7%). Response rates (52% vs. 68%) and pathologic complete responses (32% vs. 25%) were similar in both groups. CONCLUSIONS. The addition of G-CSF to this platinum-based chemotherapy regimen in patients with advanced ovarian carcinoma resulted in a modest increment in platinum dose intensity and appeared to reduce the incidence of Grade 3-4 neutropenia.