Drug-induced lupus associated with COL-3 - Report of 3 cases

Background: Anti-angiogenesis is an exciting new approach to anticancer the rapy. COL-3, a tetracycline derivative, is a novel anti-angiogenesis agent with potent preclinical anticancer activity. During the conduce of a phase 1 clinical trial for refractory metastatic cancer at the National institute s of Health, we observed 3 individuals who developed phototoxicity followed by clinical and laboratory features of drug-induced lupus. Observations: Three of 35 patients treated with COL-3 developed sunburnlike eruptions accompanied by fever and a positive antinuclear antibody titer w ithin 8 to 29 days of starting treatment. Two of: 3 had positive antihiston e antibody levels and arthralgia. One patient had marked systemic manifesta tions including pulmonary infiltrates and elevated erythrocyte sedimentatio n rate remittent for more than 1 year after discontinuing COL-3 treatment. The other 2 patients' symptoms and rash abated within 2 weeks of discontinu ing therapy although the serologic markers remained abnormal for the durati on of follow-up. Conclusions: COL-3 is the second tetracycline derivative to be implicated i n the development of drug-induced lupus. A sunburnlike eruption immediately preceded or accompanied the systemic and serologic changes in these 3 pati ents. The rapid onset and the phototoxic appearance of the accompanying eru ptions might suggest that damage to the keratinocytes caused the formation of neoantigens to which autoantibodies formed.