Activity and toxicity of 4'-iodo-4'-deoxydoxorubicin in patients with advanced breast cancer.

Based on our previous Phase I study indicating good tolerability of the drug, we have evaluated therapeutic activity and acute and subacute toxicities associated with repeated courses of the new anthracycline 4'-iodo-4'-deoxydoxorubicin (I-Dox) at the maximum tolerated dose (80 mg/m2) every three weeks. Thirty-three patients (31 evaluated for activity and 32 for toxicity) with relapsed (11 cases) or advanced breast cancer at presentation (22 cases) were treated with 108 cycles (median 3, range 1-7) for a median cumulative dose of 240 mg/m2. We observed no complete and 11 (35%) partial responses. Minor response was documented in 5 additional patients. The most frequent and severe toxicity was hematological. In 47% of the cycles and 34% of the patients I-Dox administration was associated with WHO grade 4 neutropenia. Severe neutropenia was more frequent after repeated cycles. Similar cumulative toxicity was observed for thrombocytopenia and anemia. In three patients (7 cycles) fever and possible infection occurred during neutropenia and required oral antibiotics. Extra-hematological side-effects were limited to mild/moderate nausea lasting for a few hours and mild fatigue lasting 1-7 days. Alopecia or oral mucositis were minimal or absent in the majority of patients. One case of potential reversible cardiac toxicity was observed after 240 mg/m2 I-Dox in a patient with preexistent cardiac risk factors. In view of the reported activity, good general tolerability, and selective hematological toxicity, I-Dox should be evaluated at higher than the conventionally defined maximum tolerated dose in combination with recombinant human hemopoietic growth factors.