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Thalidomide May Enhance Response Rate of Metastatic Colorectal Cancer to Irinotecan

Thalidomide May Enhance Response Rate of Metastatic Colorectal Cancer to Irinotecan

LITTLE ROCK, Arkansas—The antiangiogenic properties of thalidomide
(Thalomid) as well as its ability to inhibit tumor necrosis factor-alpha
(TNF-alpha) suggest that thalidomide might be a useful addition to regimens for
treating advanced cancers. Rangaswamy Govindarajan, MD, said that thalidomide
may enhance the response rate of metastatic colorectal cancer to irinotecan
(Camptosar) while also reducing irinotecan-related gastrointestinal toxicities.
Dr. Govindarajan is assistant professor of medicine at the University of
Arkansas for Medical Science in Little Rock, Arkansas.

In stage 2 colorectal cancer, recurrence risk is correlated to angiogenesis.
This has been demonstrated both with microvessel counts and with expression of
vascular endothelial growth factor (VEGF). Thalidomide also has a number of
effects on immune function, including inhibiting TNF-alpha and stimulating CD8+
T-lymphocytes. "Thalidomide’s immune modulating properties may be more
important than its antiangiogenic effects in cancer treatment," Dr.
Govindarajan said.

Experimental Use

Dr. Govindarajan discussed experimental use of thalidomide to treat a
patient with stage IV colon cancer who had developed liver metastases after
resection and adjuvant therapy with the Mayo Clinic 5-fluorouracil/leucovorin
regimen. After radiofrequency ablation of liver metastases and three cycles of
floxuridine, the patient developed lung metastases and worsening of liver
metastases. He was then treated with irinotecan (325 mg/m² IV q 21 d) and
thalidomide (400 mg/d PO) for three cycles with marked resolution of pulmonary
metastasis and a decrease in the size of liver metastases.

Three more cycles of treatment were given and produced remission with no
evidence of disease on CT scan. This patient remained in remission for 6 months
on thalidomide maintenance treatment (400 mg/d) then relapsed with brain
metastases.

This experience inspired a pilot study of thalidomide and irinotecan in 11
patients. Dr. Govindarajan said that treatment produced 3 complete remissions
(CR) lasting 6 to 15 months and one partial remission (PR) lasting 20 months.
"Nausea, vomiting, and diarrhea were all significantly less than would be
expected with irinotecan alone," he said.

GI Toxicities Reduced

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