title: A randomised phase II study of two different schedules of pegylated liposomal doxorubicin in metastatic breast cancer (EORTC-10993).
abstract: One hundred and sixteen women with measurable metastatic breast cancer participated in a randomised phase II study of single agent liposomal pegylated doxorubicin (Caelyx) given either as a 60 mg/m2 every 6 weeks (ARM A) or 50 mg/m2 every 4 weeks (ARM B) schedule. Patients were over 65 years of age or, if younger, had refused or been unsuitable for standard anthracyclines. The aims of the study were to evaluate toxicity and dose delivery with the two schedules and obtain further information on the response rate of liposomal pegylated doxorubicin as a single agent in anthracycline nai ve advanced breast cancer. Twenty-six patients had received prior adjuvant chemotherapy (including an anthracycline in 10). Sixteen had received non-anthracycline-based first-line chemotherapy for advanced disease. One hundred and eleven patients were evaluable for toxicity and 106 for response. The delivered dose intensity (DI) was 9.8 mg/m2 (95% CI, 7.2-10.4) with 37 (69%) achieving a DI of >90% on ARM A and 11.9 mg/m2 (95% CI, 7.5-12.8) with 37 (65%) achieving a DI of >90% on ARM B. The adverse event profiles of the two schedules were distinctly different. Mucositis was more common with the every 6 weeks regimen (35% CTC grade 3/4 in ARM A, 14% in ARM B) but palmar plantar erythrodysesthesia (PPE) was more frequent with the every 4 weeks regimen (2% CTC grade 3/4 in ARM A, 16% in ARM B). Confirmed objective partial responses by RECIST criteria were seen with both schedules; 15/51 (29%) on ARM A and 17/56 (31%) on ARM B. Liposomal pegylated doxorubicin showed significant activity in advanced breast cancer with a generally favourable side-effect profile. The high frequency of stomatitis seen with 6 weekly treatment makes this the less preferred of the two schedules tested.
authors.affiliation: Cancer Research Centre, YCR Department of Clinical Oncology, Weston Park Hospital, Sheffield S10 2SJ, UK. r.e.coleman@sheffield.ac.uk
authors.forename: R E
authors.initials: RE
authors.lastname: Coleman
authors.forename: L
authors.initials: L
authors.lastname: Biganzoli
authors.forename: P
authors.initials: P
authors.lastname: Canney
authors.forename: L
authors.initials: L
authors.lastname: Dirix
authors.forename: L
authors.initials: L
authors.lastname: Mauriac
authors.forename: P
authors.initials: P
authors.lastname: Chollet
authors.forename: V
authors.initials: V
authors.lastname: Batter
authors.forename: E
authors.initials: E
authors.lastname: Ngalula-Kabanga
authors.forename: C
authors.initials: C
authors.lastname: Dittrich
authors.forename: M
authors.initials: M
authors.lastname: Piccart
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008081:Liposomes / Q000627:therapeutic use; D008875:Middle Aged; D009362:Neoplasm Metastasis
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D004317:Doxorubicin