Iododoxorubicin in advanced breast cancer: a phase II evaluation of clinical activity, pharmacology and quality of life.
Iododoxorubicin 80 mg m-2 i.v. was given 3 weekly for a maximum of six cycles as first-line chemotherapy to 14 evaluable women with metastatic breast cancer. The response rate was 14% (95% confidence intervals 4-40%); median time to progression was 3.5 months (range 0.7 to > 9.3) and median survival was 10.2 months (range 2.3 to > 20.4). Neutropenia was the main toxicity but was not associated with severe sepsis. Two patients had a significant (> 10%) but asymptomatic fall in cardiac ejection fraction; other toxicities were mild. Plasma pharmacokinetics was studied during the first cycle of treatment. Iododoxorubicin was extensively metabolised to iododoxorubicinol. Neutropenia and thrombocytopenia were both significantly correlated with the area under the concentration-time curve (AUC) for iododoxorubicin and the total AUC for iododoxorubicin and iododoxorubicinol. Quality of life (QOL), evaluated by self-report questionnaire and interview, showed little evidence of benefit in terms of physical symptom relief, level of activity, psychological symptoms or global evaluation of QOL during treatment. Iododoxorubicin is subjectively less toxic than standard anthracyclines, but at the dose and schedule used has limited activity in metastatic breast cancer, possibly because iododoxorubicinol is not clinically active.
Twelves
C J
CJ
Imperial Cancer Research Fund Clinical Oncology Unit, United Medical School, Guy's Hospital, London, UK.
Dobbs
N A
NA
Lawrence
M A
MA
Ramirez
A J
AJ
Summerhayes
M
M
Richards
M A
MA
Towlson
K E
KE
Rubens
R D
RD
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000473:pathology; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000473:pathology; D004317:Doxorubicin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009503:Neutropenia / Q000209:etiology; D011788:Quality of Life; D016019:Survival Analysis
C053044:4'-deoxy-4'-iododoxorubicin; D004317:Doxorubicin