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Drug-induced lupus associated with COL-3: report of 3 cases
J V Ghate1, M L Turner, M A Rudek
1Dermatology Branch, National Institutes of Health, Bldg 10, Room 12N238, Bethesda, MD 20892-1908, USA.
Background:
Anti-angiogenesis is an exciting new approach to anticancer therapy. COL-3, a tetracycline derivative, is a novel anti-angiogenesis agent with potent preclinical anticancer activity. During the conduct of a phase 1 clinical trial for refractory metastatic cancer at the National Institutes 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 within 8 to 29 days of starting treatment. Two of 3 had positive antihistone antibody levels and arthralgia. One patient had marked systemic manifestations including pulmonary infiltrates and elevated erythrocyte sedimentation rate remittent for more than 1 year after discontinuing COL-3 treatment. The other 2 patients' symptoms and rash abated within 2 weeks of discontinuing therapy although the serologic markers remained abnormal for the duration of follow-up.
Conclusions:
COL-3 is the second tetracycline derivative to be implicated in the development of drug-induced lupus. A sunburnlike eruption immediately preceded or accompanied the systemic and serologic changes in these 3 patients. The rapid onset and the phototoxic appearance of the accompanying eruptions might suggest that damage to the keratinocytes caused the formation of neoantigens to which autoantibodies formed.
Insights
COL-3, an anti-angiogenesis drug, caused phototoxicity and drug-induced lupus in three patients during a clinical trial. Symptoms included sunburn-like rashes and positive autoantibodies, indicating potential risks with this cancer therapy.
Area of Science:
- Oncology
- Immunology
- Dermatology
Background:
- COL-3 is a novel tetracycline derivative investigated as an anti-angiogenesis agent for anticancer therapy.
- A phase 1 clinical trial evaluated COL-3 in patients with refractory metastatic cancer.
- Preclinical studies demonstrated potent anticancer activity for COL-3.
Observation:
- Three out of 35 patients developed sunburn-like eruptions, fever, and positive antinuclear antibody titers within 8 to 29 days of COL-3 treatment.
- Two patients exhibited positive antihistone antibody levels and arthralgia.
- One patient experienced severe systemic manifestations, including pulmonary infiltrates, persisting for over a year after treatment cessation.
Findings:
- COL-3 is implicated as the second tetracycline derivative causing drug-induced lupus.
- A phototoxic, sunburn-like eruption preceded or accompanied systemic and serologic lupus features in affected patients.
- Keratinocyte damage from phototoxicity may lead to neoantigen formation and subsequent autoantibody development.
Implications:
- COL-3 treatment carries a risk of inducing phototoxicity and drug-induced lupus.
- Early recognition of phototoxic reactions is crucial for managing potential lupus development.
- Further research into the mechanism of COL-3-induced autoimmunity is warranted.
