A RANDOMIZED DOSE INTENSITY STUDY IN OVARIAN-CARCINOMA COMPARING CHEMOTHERAPY GIVEN AT 4 WEEK INTERVALS FOR 6 CYCLES WITH HALF DOSE CHEMOTHERAPY GIVEN FOR 12 CYCLES

Background: The importance of dose intensity has not been clearly defi ned in ovarian cancer and we present a prospectively randomised trial of dose intensity in patients with ovarian cancer. Patients and method s: Ninety-nine patients with FIGO stage Ic, II, III and IV epithelial ovarian cancer were randomised to receive cycles of standard dose cycl ophosphamide (600 mg/m2) and carboplatin (300 mg/m2) alternating with adriamycin (50 mg/m2) and ifosfamide (5 G/m2) for 6 cycles at monthly intervals (49 patients) or cycles of half dose cyclophosphamide (300 m g/m2) and carboplatin (150 mg/m2) alternating with adriamycin (25 mg/m 2) and ifosfamide (2.5 G/m2) for 12 cycles at monthly intervals (50 pa tients). Patients in each arm were well balanced for major prognostic factors. Results: The combined clinical response rate (complete respon se and partial response) on the 6 month arm was 76% compared with 48% on the low dose intensity arm (p = 0.009). With a median follow up of. 25.7 months the median survival on the low dose intensity arm is 20.9 months. The median survival point on the 6 month arm has not yet been reached. The median progression free interval on the 12 month arm was 19.8 months, the median value has not yet been reached on the standar d arm. The amount of residual tumour following initial laparotomy was the only significant independent variable affecting survival (p = 0.00 01). The mean received dose intensity of each drug was greater than 80 % of the planned dose intensity. More patients had clinical disease pr ogression during treatment on the low dose intensity arm (42%) when co mpared to the standard dose intensity arm (8%) (p = 0.0003). Fifteen p atients on the standard dose arm experienced a total of 18 delays and 5 patients on the low dose arm experienced 17 delays. Nausea, vomiting and diarrhoea were similar for both standard and low dose cycles of c hemotherapy with a consequent benefit for patients receiving fewer cyc les even though these were of higher dose. Conclusions: The combinatio n studied was more effective when given at the higher dose intensity a nd the improved response and survival was not accompanied by a signifi cant increase in toxicity.