Loading…
Treatment of Metastatic Cancer with Tetrathiomolybdate, an Anticopper, Antiangiogenic Agent: Phase I Study
Preclinical and in vitro studies have determined that copper is an important cofactor for angiogenesis. Tetrathiomolybdate (TM) was developed as an effective anticopper therapy for the initial treatment of Wilson’s disease, an autosomal recessive disorder that leads to abnormal copper accumulation....
Saved in:
Published in: | Clinical cancer research 2000-01, Vol.6 (1), p.1-10 |
---|---|
Main Authors: | , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | Preclinical
and in vitro studies have determined that copper is an
important cofactor for angiogenesis. Tetrathiomolybdate (TM) was
developed as an effective anticopper therapy for the initial treatment
of Wilson’s disease, an autosomal recessive disorder that leads to
abnormal copper accumulation. Given the potency and uniqueness of the
anticopper action of TM and its lack of toxicity, we hypothesized that
TM would be a suitable agent to achieve and maintain mild copper
deficiency to impair neovascularization in metastatic solid tumors.
Following preclinical work that showed efficacy for this anticopper
approach in mouse tumor models, we carried out a Phase I clinical trial
in 18 patients with metastatic cancer who were enrolled at three dose
levels of oral TM (90, 105, and 120 mg/day) administered in six divided
doses with and in-between meals. Serum ceruloplasmin (Cp) was used as a
surrogate marker for total body copper. Because anemia is the first
clinical sign of copper deficiency, the goal of the study was to reduce
Cp to 20% of baseline value without reducing hematocrit below 80% of
baseline. Cp is a reliable and sensitive measure of copper status, and
TM was nontoxic when Cp was reduced to 15–20% of baseline. The level
III dose of TM (120 mg/day) was effective in reaching the target Cp
without added toxicity. TM-induced mild copper deficiency achieved
stable disease in five of six patients who were copper deficient at the
target range for at least 90 days. |
---|---|
ISSN: | 1078-0432 1557-3265 |