title: Combined oral topotecan plus carboplatin in relapsed or advanced cervical cancer: a GINECO phase I-II trial.
abstract: OBJECTIVE
  Combined cisplatin-topotecan therapy is standard care for advanced cervical cancer, however it is associated with haematotoxicity and nephrotoxicity. This trial was designed to assess the combination of carboplatin which is less nephrotoxic, and oral topotecan.
  
  
  METHODS
  Patients with advanced/recurrent squamous cervical cancer received carboplatin (AUC5) on day 1, with escalating oral topotecan (3.0 mg/m(2) starting dose) on days 1, 8 and 15, every 4 weeks. Endpoints were the maximal tolerated dose for the phase I part and safety profiles and response rates for the phase II part of the study.
  
  
  RESULTS
  Two dose levels were evaluated. A total of 18 patients (6 phase I, 12 phase II) were treated. The maximal tolerated dose was 3.0 mg/m(2) topotecan with carboplatin AUC5. Phase II accrual was interrupted following unacceptable toxicity, with 10 therapy-related related serious events in 9 out of 12 patients: grade 3-4 pancytopenia (7), febrile neutropenia (1), grade 3 haemorrhage (1) and grade 3 vomiting (1).
  
  
  CONCLUSIONS
  Weekly oral topotecan combined with carboplatin is associated with unmanageable toxicity and is not recommended. Future studies are warranted to better understand the toxicity of such a combination and explore alternative combinations for advanced cervical cancer.
authors.affiliation: Oncology and Haematology Department, Hautepierre Hospital, 1 Av Molière, 67098 Strasbourg, France. j-emmanuel.kurtz@chru-strasbourg.fr
authors.forename: J E
authors.initials: JE
authors.lastname: Kurtz
authors.forename: G
authors.initials: G
authors.lastname: Freyer
authors.forename: F
authors.initials: F
authors.lastname: Joly
authors.forename: L
authors.initials: L
authors.lastname: Gladieff
authors.forename: M C
authors.initials: MC
authors.lastname: Kaminski
authors.forename: M
authors.initials: M
authors.lastname: Fabbro
authors.forename: A
authors.initials: A
authors.lastname: Floquet
authors.forename: A C
authors.initials: AC
authors.lastname: Hardy-Bessard
authors.forename: N
authors.initials: N
authors.lastname: Raban
authors.forename: I
authors.initials: I
authors.lastname: Ray-Coquard
authors.forename: E
authors.initials: E
authors.lastname: Pujade-Lauraine
mesh_terms: D000284:Administration, Oral; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D012008:Recurrence; D019772:Topotecan / Q000008:administration & dosage; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D019772:Topotecan; D016190:Carboplatin