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 metastat ic 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 p atients had a significant (>10%) but asymptomatic fall in cardiac ejec tion fraction; other toxicities were mild. Plasma pharmacokinetics was studied during the first cycle of treatment. Iododoxorubicin was exte nsively metabolised to iododoxorubicinol. Neutropenia and thrombocytop enia were both significantly correlated with the area under the concen tration-time curve (AUC) for iododoxorubicin and the total AUC for iod odoxorubicin and iododoxorubicinol. Quality of life (QOL), evaluated b y self-report questionnaire and interview, showed little evidence of b enefit in terms of physical symptom relief, level of activity, psychol ogical symptoms or global evaluation of QOL during treatment. Iododoxo rubicin is subjectively less toxic than standard anthracyclines, but a t the dose and schedule used has limited activity in metastatic breast cancer, possibly because iododoxorubicinol is not clinically active.