title: A study of ovarian cancer patients treated with dose-intensive chemotherapy supported with peripheral blood progenitor cells mobilised by filgrastim and cyclophosphamide.
abstract: We have shown that large numbers of haemopoietic progenitor cells are mobilised into the blood after filgrastim [granulocyte colony-stimulating factor (G-CSF)] alone and filgrastim following cyclophosphamide chemotherapy in previously untreated patients with ovarian cancer. These cells may be used to provide safe and effective haemopoietic rescue following dose-intensive chemotherapy. Using filgrastim alone (10 micrograms kg-1), the apheresis harvest contained a median CFU-GM count of 45 x 10(4) kg-1 and 2 x 10(6) kg-1 CD34+ cells. Treatment with filgrastim (5 micrograms kg-1) following cyclophosphamide (3 g m-2) resulted in a harvest containing 66 x 10(4) kg-1 CFU-GM and 2.4 x 10(6) kg-1 CD34+ cells. There was no statistically significant difference between these two mobilising regimens. We have also demonstrated that dose-intensive carboplatin and cyclophosphamide chemotherapy can be delivered safely to patients with ovarian cancer when supported by peripheral blood progenitor cells and filgrastim. Carboplatin (AUC 7.5) and cyclophosphamide (900 mg m-2) given at 3 weekly intervals with progenitor cell and growth factor support was well tolerated in terms of haematological and systemic side-effects. Double the dose intensity of chemotherapy was delivered compared with our standard dose regimen when the treatment was given at 3 weekly intervals. Median dose intensity could be further escalated to 2.33 compared with our standard regimen by decreasing the interval between treatment cycles to 2 weeks. However, at this dose intensity less than a third of patients received their planned treatment on time. All the delays were due to thrombocytopenia.
authors.affiliation: Cancer Research Campaign Department of Medical Oncology, Christie Hospital, Manchester, UK.
authors.forename: A
authors.initials: A
authors.lastname: Weaver
authors.forename: E
authors.initials: E
authors.lastname: Wrigley
authors.forename: A
authors.initials: A
authors.lastname: Watson
authors.forename: J
authors.initials: J
authors.lastname: Chang
authors.forename: C D
authors.initials: CD
authors.lastname: Collins
authors.forename: B
authors.initials: B
authors.lastname: Jenkins
authors.forename: C
authors.initials: C
authors.lastname: Gill
authors.forename: R
authors.initials: R
authors.lastname: Pettengell
authors.forename: T M
authors.initials: TM
authors.lastname: Dexter
authors.forename: N G
authors.initials: NG
authors.lastname: Testa
authors.forename: D
authors.initials: D
authors.lastname: Crowther
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001781:Blood Component Removal / Q000379:methods; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004334:Drug Administration Schedule; D003875:Drug Eruptions / Q000209:etiology; D005260:Female; D005334:Fever / Q000209:etiology; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000494:pharmacology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy*; D011994:Recombinant Proteins
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; D016190:Carboplatin; D000069585:Filgrastim