Cancer Treatment Today » GE Junction Cancer

Erbitux for gastric cancer – pro

M Levin, MD — Wed, 29 May 2013 02:13:57 +0000

Epidermal growth factor receptor (EGFR) is over-expressed in a significant proportion of esophageal and gastric carcinomas and there has been significant interest in targeting it. Unfortunately, it has not yet shown much progress. A phase II study by Chan et al showed minimal clinical activity of cetuximab. A recent phase III trial, EXPAND (Erbitux in Combination With Xeloda and Cisplatin in Advanced Esophagogastric Cancer), involved 904 patients in 24 countries in Asia Pacific, Europe, and Latin America, and in Japan. Patients had unresectable advanced cancer of the stomach or gastroesophageal junction, and had received no previous chemotherapy or radiotherapy. Patient outcome was similar between treatment groups and the primary and secondary endpoints were not met; progression-free survival was 4.4 versus 5.6 months and overall survival was 9.4 versus 10.7 months with cetuximab combination and control treatment, respectively. Overall response rates were 29% with cetuximab and 30% with control. Cetuximab is not listed by NCCN on p. GAST-E.

Moehler M, Galle PR, Gockel I, et al. The multidisciplinary management of gastrointestinal cancer. Multimodal treatment of gastric cancer. Best Pract Res Clin Gastroenterol. 2007;21(6):965-981.

Pinto C, Di Fabio F, Siena S, et al. Phase II study of cetuximab in combination with FOLFIRI in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma (FOLCETUX study). Ann Oncol. 2007;18(3):510-517.

J.A.Chan et al, A multicenter phase II trial of single-agent cetuximab in advanced esophageal and gastric adenocarcinoma

Jan Kulig et al, Targeted therapy for gastric cancer–current status J Oncol Pharm Pract (2013) 19(1): 75-81

For Erbitux in other cancers besides colon cancer, see here, here and here

For Lay version see here

Tykerb gastric cancer – pro

M Levin, MD — Fri, 02 Nov 2012 12:19:25 +0000

Gastric cancer is known to have amplification of the ErbB2 (HER2) gene and Herceptin is supported for use in gastric cancer. Recently, there has been an interest in using Tyker(lapatinib) which is a drug that utalizes the same mechanism of action as Herceptin. One such trial is: LOGiC – Lapatinib Optimization Study in ErbB2 (HER2) Positive Gastric Cancer: A Phase III Global, Blinded Study Designed to Evaluate Clinical Endpoints and Safety of Chemotherapy Plus Lapatinib. This is an international multi-center trial that will enroll patients with locally advanced, unresectable, or metastatic gastric, esophageal, or gastro-esophageal junction cancer whose tumors have amplification of the ErbB2 (HER2) gene. The trial will investigate whether lapatinib, when added to the chemotherapy regimen, capecitabine plus oxaliplatin (CapeOx), extends the time to progression and overall survival. CapeOx is administered to all patients, and patients will be randomly assigned to receive either lapatinib or placebo. There is evidence of effectiveness for brian metastases, at least in breast cancer(Lin et al).

Iqbal et al showed that Tykerb is an effective first line drug. The evidence thus far suggests that the combination of lapatinib + capecitabine shows promising efficacy and is well tolerated as 1st line treatment for advanced GC(Pishvaian et al). The same appears to be true of paclitaxel and lapatinib and studies of this combination are ongoing.

A number of issues remain to study: the type of combination therapy, the role of Taykeb in patients previousely treated with Herceptin, and efficacy in brain mets of patients with gastric cancer.

S. Iqbal et al, Southwest Oncology Group study S0413: a phase II trial of lapatinib (GW572016) as first-line therapy in patients with advanced or metastatic gastric cancer Ann Oncol (2011) 22 (12): 2610-2615

Power, D. G., Kelsen, D. P & Shah, M. A. Advanced gastric cancer—slow but steady progress. Cancer Treat. Rev. 36, 384-392 (2010).

Ku, G. Y. & Ilson, D. H. Esophagogastric cancer: targeted agents. Cancer Treat. Rev. 36, 235-248 (2010).

Grothey, A. EGFR antibodies in colorectal cancer: where do they belong? J. Clin. Oncol. 28, 4668-4670 (2010).

M. Pishvaian, D. Sakaeva, R. K. Hsieh, S. Y. Rha, G. Caderillo-Ruiz, W. H. Miller Jr., A. M. Kemner, Y. M. Nagarwala, W. Zhang, H. Lenz; Georgetown University Medical Center, Washington, DC; Clinical Oncology Dispensary of the Republic of Bashkortostan, Ufa, Russia; Mackay Memorial Hospital, Taipei, Taiwan; Yonsei Cancer Center, Cancer Metastasis Research Center, Yonsei University College of Medicine, Seoul, South Korea; Deparment of Medical Oncology, Instituto Nacional de Cancerologia, Tlalpan, Mexico; Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, QC, Canada; GlaxoSmithKline, Collegeville, PA; University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA A global, multicenter phase II trial of lapatinib plus capecitabine in gastric cancer. J Clin Oncol 29: 2011 (suppl 4; abstr 88)

Lin NU, Diéras V, Paul D, Lossignol D, Christodoulou C, Stemmler HJ, Roché H, Liu MC, Greil R, Ciruelos E, Loibl S, Gori S, Wardley A, Yardley D, Brufsky A, Blum JL, Rubin SD, Dharan B, Steplewski K, Zembryki D, Oliva C, Roychowdhury D, Paoletti P, Winer EP. Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer. Clin Cancer Res. 2009 Feb 15;15(4):1452-9.

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C-MET as target for GE Junction cancer – pro

M Levin, MD — Thu, 06 Sep 2012 01:07:20 +0000

Gatrointestinal junction(GE) cancer (where esophagus and stomach meet) is a type of cancer that has similarities to both gastric and esophageal cancer. Since GE Junctions cancers that express HER turned out to respond well to Herceptin, there is great interest in targeting other molecules, such as the epidermal growth factor receptor, vascular endothelial growth factor receptor, and P13k/Akt/mTor pathway, as well as the insulin-like growth factor receptor, c-Met pathways, fibroblast growth factor receptor, and other pathways in this type of cancer. Much remains to be done before clinical therapies based on this concept become available and proven but there is much research activity. One study looking at a C-MET inhibitor is: MET111643 ,A Phase 2 Study of GSK1363089 (XL880) Administered Orally to Subjects with Metastatic Gastric Cancer.

Jochen K. Lennerz, Eunice L. Kwak, Allison Ackerman, Michael Michael, Stephen B. Fox, Kristin Bergethon, Gregory Y. Lauwers, James G. Christensen, Keith D. Wilner, Daniel MET Amplification Identifies a Small and Aggressive Subgroup of Esophagogastric Adenocarcinoma With Evidence of Responsiveness to Crizotinib, JCO VOLUME 29 NUMBER 36 DECEMBER 20 2011

Ajani JA: Gastroesophageal cancers: Progress and problems. J Natl Compr Canc Netw 6:813-814, 2008

nccn.org, Gastric cancer 2012

Research in GE Junction Gastric Cancer – pro

M Levin, MD — Mon, 13 Aug 2012 14:01:28 +0000

C-MET as target for GE Junction cancer

Since GE Junctions cacners that express HER respond well to Herceptin, there is great interest in targeting molecules, such as the epidermal growth factor receptor, vascular endothelial growth factor receptor, and P13k/Akt/mTor pathway, as well as the insulin-like growth factor receptor, c-Met pathways, fibroblast growth factor receptor, and other pathways. Much remians to be done before clinical therapies based on this concept become available and proven. One study looking at a C-MET inhibitor is: MET111643 ,A Phase 2 Study of GSK1363089 (XL880) Administered Orally to Subjects with Metastatic Gastric Cancer.

Ajani JA: Gastroesophageal cancers: Progress and problems. J Natl Compr Canc Netw 6:813-814, 2008

nccn.org, Gastric cancer 2012

Read the Layperson version here.