title: 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.
abstract: 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.
  
  
  METHODS
  Patients with untreated stage IC-IV ovarian cancer received six cycles of carboplatin area under the curve 6 (AUC 6) 3 weekly either with no dose modification except for toxicity (Arm A) or with dose escalations in cycles 2-6 based on nadir neutrophil and platelet counts (Arm B). The primary end-point was progression-free survival (PFS).
  
  
  RESULTS
  Nine hundred and sixty-four patients were recruited from 71 centers. Dose escalation was achieved in 77% of patients who had ≥1 cycle. The median AUCs (cycle 2-6) received were 6.0 (Arm A) and 7.2 (Arm B) (P < 0.001). Grade 3/4 non-hematological toxicity was higher in Arm B (31% versus 22% P = 0.001). The median PFS was 12.1 months in Arm A and B [hazard ratio (HR) 0.99; 95% confidence interval (CI) 0.85-1.15; P = 0.93]. 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). In multivariate analysis, baseline neutrophil (P < 0.001), 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 counts is feasible and safe. However, it provided no improvement in PFS or OS compared with flat dosing. Baseline neutrophils over-ride nadir counts in prognostic significance. These data may have wider implications particularly in respect of the management of chemotherapy-induced neutropenia.
authors.affiliation: Department of Medicine,  Royal Marsden Hospital NHS Foundation Trust and Institute of Cancer Research, London.
authors.forename: S
authors.initials: S
authors.lastname: Banerjee
authors.forename: G
authors.initials: G
authors.lastname: Rustin
authors.forename: J
authors.initials: J
authors.lastname: Paul
authors.forename: C
authors.initials: C
authors.lastname: Williams
authors.forename: S
authors.initials: S
authors.lastname: Pledge
authors.forename: H
authors.initials: H
authors.lastname: Gabra
authors.forename: G
authors.initials: G
authors.lastname: Skailes
authors.forename: A
authors.initials: A
authors.lastname: Lamont
authors.forename: A
authors.initials: A
authors.lastname: Hindley
authors.forename: G
authors.initials: G
authors.lastname: Goss
authors.forename: E
authors.initials: E
authors.lastname: Gilby
authors.forename: M
authors.initials: M
authors.lastname: Hogg
authors.forename: P
authors.initials: P
authors.lastname: Harper
authors.forename: E
authors.initials: E
authors.lastname: Kipps
authors.forename: L-A
authors.initials: LA
authors.lastname: Lewsley
authors.forename: M
authors.initials: M
authors.lastname: Hall
authors.forename: P
authors.initials: P
authors.lastname: Vasey
authors.forename: S B
authors.initials: SB
authors.lastname: Kaye
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage*; D000077216:Carcinoma, Ovarian Epithelial; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin