A pilot trial of the anti-angiogenic copper lowering agent tetrathiomolybdate in combination with irinotecan, 5-flurouracil, and leucovorin for metastatic colorectal cancer.
Tetrathiomolybdate (TM) is an oral copper chelator under development as an anti-angiogenic agent. We evaluated TM in combination with irinotecan, 5-fluorouracil, and leucovorin (IFL). Serum vascular endothelial growth factor (VEGF), basic fibroblast growth factor, interleukin 6 (IL-6), and IL-8 were measured to evaluate the anti-angiogenic effect. Twenty-four patients with metastatic colorectal cancer were treated. The combination with IFL was well tolerated and dose intensity of IFL was maintained during combination therapy with TM. By intention to treat analysis, the overall response rate (RR) was 25% (95% CI 9.8-46.7) and the median time to progression (TTP) was 5.6 months (95% CI 2.7-7.7). VEGF levels were correlated with TTP, as were changes in VEGF, IL-8, and IL-6. TM can be safely added to IFL without compromising dose intensity or diminishing the expected RR. Changes in serum VEGF, IL-8, and IL-6 after treatment may directly reflect changes in CRC tissue angiogenesis.
Gartner
Elaina M
EM
Wayne State University, 4100 John R, 4HWCRC, Detroit, MI 48108, USA. gartnere@karmanos.org
Griffith
Kent A
KA
Pan
Quintin
Q
Brewer
George J
GJ
Henja
Gwen F
GF
Merajver
Sofia D
SD
Zalupski
Mark M
MM
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D002614:Chelating Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003300:Copper / Q000378:metabolism*; D016207:Cytokines / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D008982:Molybdenum / Q000008:administration & dosage / Q000627:therapeutic use*; D009362:Neoplasm Metastasis; D010865:Pilot Projects
D020533:Angiogenesis Inhibitors; D002614:Chelating Agents; D016207:Cytokines; D003300:Copper; D008982:Molybdenum; C020809:tetrathiomolybdate; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin