Gastroenterol Res

Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access

Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc

Journal website http://www.gastrores.org

Review

Volume 1, Number 1, December 2008, pages 14-19

Clinical Trials of Antiangiogenesis Therapy on Gastric Cancer

**Table 1.** Clinical trials of antiangiogenesis therapy in gastric cancers source (from http://clinicaltrials.gov)
1.	NCT00780494: Phase II of Capecitabine, Carboplatin & Bevacizumab for Gastroesophageal Junction & Gastric Carcinoma. Stanford University and Genentech, USA
2.	NCT00394433: Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) in Metastatic Esophageal and Gastric Cancer Dana-Farber Cancer Institute, Brigham and Women's Hospital, Massachusetts General Hospital, and Genentech, USA
3.	NCT00403468: Combination Chemotherapy and Bevacizumab in Treating Patients With Recurrent, Unresectable, or Metastatic Gastric Cancer, Gastroesophageal Junction Cancer, or Esophageal Cancer. Memorial Sloan-Kettering Cancer Center and National Cancer Institute (NCI), USA
4.	NCT00673673: FOLFOX With Bevacizumab in Metastatic or Unresectable Gastroesophageal and Gastric Cancer Yale University and Genentech, USA
5.	NCT00555672: Study Of Sunitinib In Combination With Cisplatin And 5-Fluorouracil In Patients With Advanced Gastric Cancer. Pfizer, USA
6.	NCT00555620: Study Of Sunitinib In Combination With Cisplatin/Capecitabine Or Oxaliplatin/Capecitabine In Patients With Advanced Gastric Cancer. Pfizer, USA
7.	NCT00553696: Study Of Sunitinib With S-1 And Cisplatin For Gastric Cancer Pfizer, USA
8.	NCT00524186: Sunitinib, Irinotecan, Fluorouracil, and Leucovorin In Treating Patients With Advanced Stomach Cancer or Gastroesophageal Cancer. Roswell Park Cancer Institute and National Cancer Institute (NCI), USA
9.	NCT00450203: Combination Chemotherapy With or Without Bevacizumab in Treating Patients With Previously Untreated Stomach Cancer or Gastroesophageal Junction Cancer That Can Be Removed by Surgery. National Cancer Institute (NCI), USA
10.	NCT00217581: Bevacizumab, Oxaliplatin, and Docetaxel in Treating Patients With Locally Advanced Unresectable or Metastatic Stomach or Gastroesophageal Junction Cancer. Barbara Ann Karmanos Cancer Institute and National Cancer Institute (NCI), USA
11.	NCT00350753: Avastin and Tarceva for Upper Gastrointestinal Cancers. Rigshospitalet, Denmark
12.	NCT00548548: A Study of Bevacizumab in Combination With Capecitabine and Cisplatin as First-Line Therapy in Patients With Advanced Gastric Cancer. Genentech, Hoffmann-La, Roche and Chugai, USA
13.	NCT00178698: Hyperthermia/Thermal Therapy With Chemotherapy to Treat Inoperable or Metastatic Tumors. The University of Texas Health Science Center, Houston, USA
14.	NCT00447330: Xelox (Xeloda + Oxaliplatin) and Avastin for Metastatic Esophagogastric Adenocarcinoma. Duke University, Hoffmann-La Roche, Sanofi-Aventis, and Genentech, USA
15.	NCT00737438: Pre-Operative Chemotherapy Plus Bevacizumab With Early Salvage Therapy Based on PET Assessment of Response in Patients With Locally Advanced But Resectable Gastric and GEJ Adenocarcinoma.Memorial Sloan-Kettering Cancer Center and Genentech, USA
16.	NCT00390416: Study of Docetaxel, Cisplatin, and Fluorouracil (Modified DCF) With Bevacizumab in Patients With Unresectable or Metastatic Gastroesophageal Adenocarcinoma.Memorial Sloan-Kettering Cancer Center, Sanofi-Aventis, Genentech, USA
17.	NCT00172627: Association and Mechanism Between Cyclooxygenase-2 and Interleukin-6 in Gastric Cancer. National Taiwan University Hospital, Taiwan
18.	NCT00565370: Phase I/II XP+Sorafenib in Advanced Gastric Cancer. Asan Medical Center, Asian Stomach cancer Investigator Association will join in the phase II portion, Asia
19.	NCT00595972: Epirubicin Cisplatin and 5-FU Combined With Endostar in Patients With Advanced or Metastatic Gastric Cancer. Fudan University, China
20.	NCT00570531: Phase II Trial for Patients With Loco-Regional Esophageal Carcinoma..University of Michigan Cancer Center and Genentech, USA
21.	NCT00703625: Phase I Study of Docetaxel and Temsirolimus in Resistant Solid Malignancies. Washington University School of Medicine, USA

Table 1. Clinical trials of antiangiogenesis therapy in gastric cancers source (from http://clinicaltrials.gov)

NCT00780494: Phase II of Capecitabine, Carboplatin & Bevacizumab for Gastroesophageal Junction & Gastric Carcinoma. Stanford University and Genentech, USA

NCT00394433: Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) in Metastatic Esophageal and Gastric Cancer Dana-Farber Cancer Institute, Brigham and Women's Hospital, Massachusetts General Hospital, and Genentech, USA

NCT00403468: Combination Chemotherapy and Bevacizumab in Treating Patients With Recurrent, Unresectable, or Metastatic Gastric Cancer, Gastroesophageal Junction Cancer, or Esophageal Cancer. Memorial Sloan-Kettering Cancer Center and National Cancer Institute (NCI), USA

NCT00673673: FOLFOX With Bevacizumab in Metastatic or Unresectable Gastroesophageal and Gastric Cancer Yale University and Genentech, USA

NCT00555672: Study Of Sunitinib In Combination With Cisplatin And 5-Fluorouracil In Patients With Advanced Gastric Cancer. Pfizer, USA

NCT00555620: Study Of Sunitinib In Combination With Cisplatin/Capecitabine Or Oxaliplatin/Capecitabine In Patients With Advanced Gastric Cancer. Pfizer, USA

NCT00553696: Study Of Sunitinib With S-1 And Cisplatin For Gastric Cancer Pfizer, USA

NCT00524186: Sunitinib, Irinotecan, Fluorouracil, and Leucovorin In Treating Patients With Advanced Stomach Cancer or Gastroesophageal Cancer. Roswell Park Cancer Institute and National Cancer Institute (NCI), USA

NCT00450203: Combination Chemotherapy With or Without Bevacizumab in Treating Patients With Previously Untreated Stomach Cancer or Gastroesophageal Junction Cancer That Can Be Removed by Surgery. National Cancer Institute (NCI), USA

10.

NCT00217581: Bevacizumab, Oxaliplatin, and Docetaxel in Treating Patients With Locally Advanced Unresectable or Metastatic Stomach or Gastroesophageal Junction Cancer. Barbara Ann Karmanos Cancer Institute and National Cancer Institute (NCI), USA

11.

NCT00350753: Avastin and Tarceva for Upper Gastrointestinal Cancers. Rigshospitalet, Denmark

12.

NCT00548548: A Study of Bevacizumab in Combination With Capecitabine and Cisplatin as First-Line Therapy in Patients With Advanced Gastric Cancer. Genentech, Hoffmann-La, Roche and Chugai, USA

13.

NCT00178698: Hyperthermia/Thermal Therapy With Chemotherapy to Treat Inoperable or Metastatic Tumors. The University of Texas Health Science Center, Houston, USA

14.

NCT00447330: Xelox (Xeloda + Oxaliplatin) and Avastin for Metastatic Esophagogastric Adenocarcinoma. Duke University, Hoffmann-La Roche, Sanofi-Aventis, and Genentech, USA

15.

NCT00737438: Pre-Operative Chemotherapy Plus Bevacizumab With Early Salvage Therapy Based on PET Assessment of Response in Patients With Locally Advanced But Resectable Gastric and GEJ Adenocarcinoma.Memorial Sloan-Kettering Cancer Center and Genentech, USA

16.

NCT00390416: Study of Docetaxel, Cisplatin, and Fluorouracil (Modified DCF) With Bevacizumab in Patients With Unresectable or Metastatic Gastroesophageal Adenocarcinoma.Memorial Sloan-Kettering Cancer Center, Sanofi-Aventis, Genentech, USA

17.

NCT00172627: Association and Mechanism Between Cyclooxygenase-2 and Interleukin-6 in Gastric Cancer. National Taiwan University Hospital, Taiwan

18.

NCT00565370: Phase I/II XP+Sorafenib in Advanced Gastric Cancer. Asan Medical Center, Asian Stomach cancer Investigator Association will join in the phase II portion, Asia

19.

NCT00595972: Epirubicin Cisplatin and 5-FU Combined With Endostar in Patients With Advanced or Metastatic Gastric Cancer. Fudan University, China

20.

NCT00570531: Phase II Trial for Patients With Loco-Regional Esophageal Carcinoma..University of Michigan Cancer Center and Genentech, USA

21.

NCT00703625: Phase I Study of Docetaxel and Temsirolimus in Resistant Solid Malignancies. Washington University School of Medicine, USA

**Table 2.** FDA-approved angiogenesis inhibitors in oncology
1. Monoclonal antibodies:
Bevacizumab (Avastin), Genentech,
Description: A humanized monoclonal antibody that binds biologically active forms of vascular endothelial growth factor (VEGF) and prevents its interaction with VEGF receptors (VEGFR-1 and VEGFR-2), thereby inhibiting endothelial cell proliferation and angiogenesis.
Approved indications: Metastatic colorectal cancer (mCRC), non-small cell lung cancer (NSCLC), advanced breast cancer.

Cetuximab (Erbitux), Bristol-Myers Squibb, ImClone
Description: A humanized monoclonal antibody that binds biologically active forms of vascular endothelial growth factor (VEGF) and prevents its interaction with VEGF receptors (VEGFR-1 and VEGFR-2), thereby inhibiting endothelial cell proliferation and angiogenesis.
Approved indications: Metastatic colorectal cancer, head and neck cancer.

2. Small molecule tyrosine kinase inhibitors:
Sorafenib (Nexavar), Bayer Onyx
Description: Small molecule TK inhibitor of of VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-ß, and Raf-1.
Approved indications: Advanced renal cell carcinoma, advanced hepatocellular carcinoma.

Sunitinib (Sutent), Pfizer
Description: Small molecule TK inhibitor of VEGFR-1, VEGFR-2, VEGFR-3, PDGFR- ß, and RET.
Approved indications: Advanced renal cell carcinoma, and gastrointestinal stromal tumor (GIST).

3. Inhibitors of mTOR:
Temsirolimus (Torisel™), Wyeth
Description: A small molecule inhibitor of mTOR (mammalian target of rapamycin), part of the PI3 kinase/AKT pathway involved in tumor cell proliferation and angiogenesis.
Approved indications: Advanced renal cell carcinoma.

Other angiogenic inhibitors:
Bortezomib (Velcade®), Millennium,
Description: A proteasome inhibitor that disrupts signaling of the cancer cell, leading to cell death and tumor regression. Bortezomib may have indirect antiangiogenic properties, although the mechanisms are unclear.
Approved indications: Multiple myeloma, mantle cell lymphoma (MCL).

Thalidomide (Thalomid®), Celgene
Description: Possesses immunomodulatory, anti-inflammatory, and antiangiogenic properties, although the precise mechanisms of action are not fully understood.
Approved indications: Multiple myeloma

Table 2. FDA-approved angiogenesis inhibitors in oncology

1. Monoclonal antibodies:

Bevacizumab (Avastin), Genentech,

Description: A humanized monoclonal antibody that binds biologically active forms of vascular endothelial growth factor (VEGF) and prevents its interaction with VEGF receptors (VEGFR-1 and VEGFR-2), thereby inhibiting endothelial cell proliferation and angiogenesis.

Approved indications: Metastatic colorectal cancer (mCRC), non-small cell lung cancer (NSCLC), advanced breast cancer.

Cetuximab (Erbitux), Bristol-Myers Squibb, ImClone

Approved indications: Metastatic colorectal cancer, head and neck cancer.

2. Small molecule tyrosine kinase inhibitors:

Sorafenib (Nexavar), Bayer Onyx

Description: Small molecule TK inhibitor of of VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-ß, and Raf-1.

Approved indications: Advanced renal cell carcinoma, advanced hepatocellular carcinoma.

Sunitinib (Sutent), Pfizer

Description: Small molecule TK inhibitor of VEGFR-1, VEGFR-2, VEGFR-3, PDGFR- ß, and RET.

Approved indications: Advanced renal cell carcinoma, and gastrointestinal stromal tumor (GIST).

3. Inhibitors of mTOR:

Temsirolimus (Torisel™), Wyeth

Description: A small molecule inhibitor of mTOR (mammalian target of rapamycin), part of the PI3 kinase/AKT pathway involved in tumor cell proliferation and angiogenesis.

Approved indications: Advanced renal cell carcinoma.

Other angiogenic inhibitors:

Bortezomib (Velcade®), Millennium,

Description: A proteasome inhibitor that disrupts signaling of the cancer cell, leading to cell death and tumor regression. Bortezomib may have indirect antiangiogenic properties, although the mechanisms are unclear.

Approved indications: Multiple myeloma, mantle cell lymphoma (MCL).

Thalidomide (Thalomid®), Celgene

Description: Possesses immunomodulatory, anti-inflammatory, and antiangiogenic properties, although the precise mechanisms of action are not fully understood.

Approved indications: Multiple myeloma