A multicenter, randomized trial of flat dosing versus intrapatient dose escalation of single-agent carboplatin as first-line chemotherapy for advanced ovarian cancer: an SGCTG (SCOTROC 4) and ANZGOG study on behalf of GCIG

Background: The aim of the study is to demonstrate that intrapatient dose escalation of carboplatin would improve the outcome in ovarian cancer compared with flat dosing. Patient and method: Patients with untreated stage IC-IV ovarian cancer received six cycles of carboplatin under the curve 6 (AUC 6) 3 weekly either with no dose modification except for toxicity (Arm A) or with dose escalations in cycles 24 based on nadir neutrophil and platelet counts (Arm 9), The primary end-point was progression-free survival (PPS). Results: Nine hundred and sixty-four patients were recruited from 71 centers, Dose oscalation was achieved in 77% of patients who had 1 cycle, The median AUCs (cycle 24) received were 6,0 Won A) and 72 Grade 3/4 non-hematological toxicity was higher in Arm 9 (31% versus 22% P=0.001), The median PFS was 12,1 months in Arm A and 9 [hazard ratio (HR) 0.00; 95% confidence interval (CI) 0.85=1.15; P = 0.03]. The median overall survival (OS) was 34.1 and 30.7 months in Arms A and B, respectively (HR 0.98; 95% CI 0.81-1.18, P = 0.82), multivariate analysis, bawling neutrophil (P < 0.441), baseline platelet counts (P < 0.001) and the difference between white blood cell (WBC) and neutrophil count (P = 0.009) had a significant adverse prognostic value. Conclusions: Intrapatient dose escalation of carboplatin based on nadir blood courts is feasible and safe, However, it provided no improvement in PPS or OS, compared with flat dosing, Baseline neutrophils over-tide nadir counts in prognostic significance, Time data may have wider implications particularly in respect of the management of chemotherapy-induced neutropenia,