OK, here are some good news (from LA JCC):
RESEARCHERS AT UCLA's JONSSON CANCER CENTER LAUNCH
NEW EXPERIMENTAL TREATMENT FOR ADVANCED COLON
CANCER USING AN ANGIOGENESIS INHIBITOR
Researchers at UCLA's Jonsson Cancer Center today are launching a new experimental treatment for advanced colon cancer, using a drug thought to attack tumors by cutting off their blood supply. UCLA is the only site worldwide offering this experimental treatment for colon cancer, researchers said.
A solid tumor cannot grow beyond the size of a pinhead unless it has an independent blood supply to deliver the oxygen and nutrients a malignancy needs to advance and spread. To feed itself, a tumor develops its own blood supply, a process called angiogenesis. Researchers hope this experimental drug works by interrupting that process, thereby cutting off the blood supply to the tumor and, hopefully, killing it.
These types of drugs, called angiogenesis inhibitors, garnered worldwide media attention last spring after they cured cancer in mice. However, researchers at UCLA's Jonsson Cancer Center already has begun testing an angiogenesis inhibitor, called SU5416, on people.
In this new study, UCLA researchers will use SU5416 in combination with the standard chemotherapy treatment for colon cancer, 5-FU (5 fluorouracil) and leucovorin. Researchers already have determined that SU5416 is safe for humans. This new study will take the drug a step further, testing it for possible interactions with other drugs, said Dr. Lee Rosen, principal investigator and head of UCLA's Cancer Therapy Development Program.
Rosen led the previous SU5416 study, which tested the drug on patients with a variety of advanced cancers. About 70 people participated in that Phase I study, which ended in December 1998.
“Colon cancer is one of the most common cancers in this country and it's been treated the same way for 40 years,” Rosen said. “We want to come up with new and better ways to treat this cancer.”
Colon cancer ranks as the third most common malignancy in the United States, behind lung and breast cancers in women and lung and prostate cancers in men, Rosen said. It is the second leading cause of cancer deaths nationwide.
About 140,000 new cases of colon cancer will be diagnosed this year. About 40 percent of cases will be fatal, according to the American Cancer Society. Although they grow slowly, colon cancers often are not detected until they have spread to other parts of the body and it's too late for effective treatment.
Rosen said he's optimistic about this experimental treatment, based on results from the previous SU5416 study. The previous study, and some of its patients, will be chronicled in a rare two-segment piece on “60 Minutes,” scheduled to air April 4, 1999.
“Because of some encouraging results, we're going forward to see how this drug works on specific diseases such as colon cancer,” Rosen said. “One of the questions we need to ask is what will this drug do when we add it to traditional chemotherapy. We hope it will make the existing treatment much better.”
To qualify for the experimental treatment at UCLA's Jonsson Cancer Center, study participants must have untreated, metastatic colon cancer, Rosen said. Participants will receive SU5416 by infusion twice a week, concurrent with the standard chemotherapy. In the previous study, SU5416 proved to have few side effects. Those that arise are easily treated with over-the-counter medications, Rosen said.
“This is a chance to try a new, exciting, cutting-edge therapy,” Rosen said. “Based on what we've seen in the lab and the hints of things we've seen in early testing, our expectations are high that this drug will be effective against colon cancer.”
If results of the study are as encouraging as hoped, a much larger, Phase III clinical trial will be launched worldwide to test SU5416 on advanced colon cancer, Rosen said.
The process of angiogenesis and its role in tumor growth remain the focus of much research, according to officials at the National Cancer Institute. More than a dozen angiogenesis inhibitors aimed at combating cancer by cutting off blood vessel growth are being tested in clinical trials nationwide, said Paul Van Nevel, a spokesman for the NCI.
SU5416 is manufactured by SUGEN Inc., a South San Francisco-based biotechnology firm. In January, SUGEN announced plans to accelerate development of SU5416, testing it on colon and lung cancers. SU5416 also is being tested on AIDS-related Kaposi's sarcoma at UCLA and other sites.
To find out more about the new experimental treatment for colon cancer, or to volunteer for the study, call (310) 794-9967.
and AACR abstract on SU6668:
SU6668 is a potent, broad spectrum angiogenesis inhibitor that exhibits anti-tumor properties. Shawver, LK, Strawn, LM, Fong, TAT, Antonian, L, Sukbuntherng, J, Powell, TJ, Lipson, K, Tang, F, Tang, C, Sun, L, Schreck, R, Wagner, GS, Hirth, KP, and McMahon, G. SUGEN, Inc., SSF, CA. 94080
The VEGF, FGF and PDGF growth factor systems are strongly implicated in angiogenesis associated with solid tumors. SU6668, a novel receptor tyrosine kinase inhibitor, inhibited autophosphorylation of multiple members of the split kinase family, VEGFR, PDGFR and FGFR (IC50 = 0.02 uM, 0.06 uM, and 1.3 uM, respectively), but not of the more distantly related EGFR (IC50>100 uM). SU6668 exerted potent antiproliferative activity on VEGF- and FGF2-stimulated mitogenesis of human endothelial cells with IC50 = 0.41 uM and 9.3 uM, respectively. This inhibition showed slow onset (8-12 hr exposure) but prolonged duration (>= 96 hr after washout). Daily administration of SU6668 in mice showed statistically significant inhibition of the growth of 6 individual subcutaneous tumor xenografts derived from varied human origin. Although SU6668 has anti-angiogenic properties, it may also act directly on tumor cells or other host tissue that supports tumor growth, as it inhibited the growth of tumor cell lines in vitro and inhibited ligand-induced BrdU incorporation into 3T3 cells. Further in vivo studies using SU6668 revealed that a dosing regimen of 2-3 times/week was efficacious, as was administration by the oral route. In rats, SU6668 demonstrated dose-independent kinetics with a low clearance value (CLs = 4-5 ml/min kg -1) and a t1/2 of 2-3 hr. The oral bioavailability of SU6668 in rats was approximately 50%. Investigations of SU6668 in human clinical trials are planned. |
