alexa
Reach Us +44-1993-227344
Is there an Increased Risk of Central Nervous System Metastasis in Cases with Gastric Cancer Showing Her2 Expression and Treated by Trastuzumab? | OMICS International
ISSN: 2165-7920
Journal of Clinical Case Reports
Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

Is there an Increased Risk of Central Nervous System Metastasis in Cases with Gastric Cancer Showing Her2 Expression and Treated by Trastuzumab?

Semra Paydas*
Department of Oncology, Faculty of Medicine, Cukurova University, Adana, Turkey
Corresponding Author : Semra Paydas
Department of Oncology
Faculty of Medicine
Cukurova University, Adana, Turkey
E-mail: [email protected]
Received August 19, 2013; Accepted Septeber 20, 2013; Published September 22, 2013
Citation: Paydas S (2013) Is there an Increased Risk of Central Nervous System Metastasis in Cases with Gastric Cancer Showing Her2 Expression and Treated by Trastuzumab? J Clin Case Rep 3:299. doi:10.4172/2165-7920.1000299
Copyright: © 2013 Paydas S. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Journal of Clinical Case Reports

Abstract

The oncogene encoding Her2 receptor which has an important biologic significance in human cancers has been described 30 years ago by Schecter et al. Her2 amplification in gastric cancer has been shown in MKN-7 gastric cancer cell line firstly by Fukushige et al. in 1986. Later studies showed variable expression of ERBB2 in gastric cancer and Her2 expression rate has been found between 8% and 54%. Significant survival advantage has been reported with the introduction of trastuzumab in cases with gastric cancer expressing ERBB2. Other anti-ERBB2 agents are used in ongoing studies and longer survival times are expected. By analogy with ERBB2 breast cancer it can be speculated that central nervous system metastases may increase in these cases with increased survival times. Here we reported brain metastases in a case with metastatic gastric cancer treated by trastuzumab containing regimen.

Introduction
The oncogene encoding Her2 receptor which has an important biologic significance in human cancers has been described 30 years ago by Schecter et al. [1]. Her2 amplification in gastric cancer has been shown in MKN-7 gastric cancer cell line firstly by Fukushige et al. in 1986 [2]. Later studies showed variable expression of ERBB2 in gastric cancer and Her2 expression rate has been found between 8% and 54% [3,4]. Significant survival advantage has been reported with the introduction of trastuzumab in cases with gastric cancer expressing ERBB2 [5]. Other anti-ERBB2 agents are used in ongoing studies and longer survival times are expected. By analogy with ERBB2 breast cancer it can be speculated that central nervous system metastases may increase in these cases with increased survival times. Here we reported brain metastases in a case with metastatic gastric cancer treated by trastuzumab containing regimen.
Case Report
62 year-old-man admitted to the hospital on June 2011 with the history of gastrointestinal bleeding and two units of blood transfusion. On physical exam there was pallor and hepatomegaly. His past medical history was negative except ten pocket years of smoking
Laboratory: Abnormal findings were Hb 6 g/dl, Hct 20%, ferritin 10.5 ng/ml.
Upper endoscopy showed 5 cm ulcerated mass at cardia and endoscopic biopsy was reported as well differentiated adeno cancer. Her2 Neu was found to be (+++) and FISH analysis showed high amplification for Her2 Neu. Serum tumor markers were found to be high; CA19.9: 653 IU and CEA: 166 IU.
PET/CT showed 7×2.5 cm mass at gatric cardia (SUV max 25.64) and multiple hepatic metastases (SUV max 22.75). There was no evidence of cerebral metastasis at CT scans (Figures 1a and 1b). He received trastuzumab plus cisplatin and fluoropyrimidine containing regimen for 8 cycles and at the end of this treatment PET/CT and tumor markers were found to be negative. Maintenance trastuzumab could not be given due to the social security reasons. After 5 months of the last dose of treatment; tumor markers were found to be increased and repeated PET/CT showed relapsed disease at gastric cardia and liver again. Cisplatin, capecitabine and trastuzumab combination was started on February 2013 and 5 cycles were given and partial response was achieved. However at the end of June (at the end of 22nd month of metastatic gastric cancer) left hemipharesis developed. Brain CT showed right parieto-occipital and fronto-parietal lesions with large peri-tumoral edema (Figure 2). Anti-edema treatment with dexamethasone and cranial irradiation were started immediately. After 10 days of cranial irradiation, his condition deteriorated rapidly. Acute renal failure and jaundice developed. Repeated abdominal image showed disseminated liver metastases. He died within two weeks after cranial irradiation. Any other anti-Her2 treatment including lapatinib could not be given due to rapid progression of the disease.
Discussion
Although there is no standard treatment for metastatic gastric cancer, platinum-fluoropyrimidine containing regimens with or without antracycline or docetaxel are the most commonly used doublets or triplets [6-8]. However with the combination of these drugs median survival is less than one year [9,10]. On the other hand, biology of gastric cancer has been found to be more important after the introduction of trastuzumab in the treatment of advanced gastric cancer. Median survival has been found to be increased in cases with ERBB2 expression and treated by trastuzumab containing regimens. ERBB2 expression rate is highest in proximal cancers and lowest in distal cancers and the most successful treatment results have been reported in high expressors [5,11,12]. The most famous study about this matter is Phase III-ToGA trial and significant overall survival advantage (10 vs 13 months) has been documented in cases receiving trastuzumab in addition to the conventional chemotherapy [5]. This study and other similar studies suggest that ERBB2 is an important therapeutic target in these cases. It can be said that 15-25% of the cases with gastroesophageal cancers show ERBB2 expression similar to the breast cancers and about one in five cases with breast cancer is candidate for anti-ERBB2 treatment modalities [13]. Our case had proximal cancer and he lived about 2 years and brain metastasis developed. What is the cause of central nervous system metastasis in our case?
1-Can it be due to the tumor biology? We do not know the exact answer but it has not been reported increased risk of central nervous system metastases in these cases in large scale multi-centric studies.
2-Can we make another comment by analogy from breast cancer? In breast cancer, there is no confirmation of correlation between trastuzumab and brain metastases and it has been suggested that systemic control of the disease with trastuzumab along with its inability to penetrate the blood-brain barrier may cause to the higher incidence of brain metastases [14]. In our case, relatively longer survival for a metastatic gastric cancer may be a cause of brain metastasis.
3-What are the therapeutic choices in these cases? In our case, we started anti-edema dexamethasone and cranial irradiation immediately due to his progressive neurologic signs and symptoms. At this point what are the available and the possible choices in this case and similar cases? Lapatinib plus capecitabine may be an important choice in our case due to the high penetrance of small molecule lapatinib to the central nervous system and higher activity of capecitabine in central nervous system disease especially after cranial irradiation [15,16]. On the other hand it has been shown that lapatinib reverses irinotecan resistance in vitro and it is reasonable to combine lapatinib and irinotecan which is an active drug in second line treatment of gastric cancer [17]. Another choice may be the combination of capecitabine, lapatinib and oxaliplatin which this regimen will be tested in LOGiC trial [13]. Trastuzumab and lapatinib combination which has been found to be effective in metastatic breast cancer may be another option [18]. Intrathecal trastuzumab may be another choice in this case.
In conclusion the occurrence of central nervous system metastasis may be seen in cases with gastric cancer showing ERBB2 expression and treated by trastuzumab containing regimens. Novel combinations and or approaches are needed in these cases.
References

Figures at a glance

Figure Figure Figure
Figure 1a Figure 1b Figure 2
Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Relevant Topics

Article Usage

  • Total views: 11788
  • [From(publication date):
    September-2013 - Nov 22, 2018]
  • Breakdown by view type
  • HTML page views : 8010
  • PDF downloads : 3778
 

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2018-19
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri and Aquaculture Journals

Dr. Krish

[email protected]

+1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

streamtajm

[email protected]

1-702-714-7001Extn: 9042

 
© 2008- 2018 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version