LITTLE ROCK, Arkansas—The antiangiogenic properties of thalidomide(Drug information on 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(Drug information on 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
