Overview of Trastuzumab’s Utility for Gastric Cancer pdf

28 | Connection 2010

Overview of Trastuzumab’s Utility

for Gastric Cancer

Judith Meza-Junco, MD

Heather-Jane Au, MD, FRCPC, MPH

Michael B. Sawyer, MD, BScPhm, FRCPC

Department of Oncology

Cross Cancer Institute

11560 University Avenue

Edmonton, Alberta, Canada, T6G 1Z2

Abstract

Gastric Cancer (GC) is the second leading cause of cancer-related

death worldwide, and has been managed with different treatment

strategies around the world. Surgery is the mainstay of treatment for

non-metastatic disease. Because recurrences are common after curative

resection, adjuvant radio-chemotherapy or perioperative chemotherapy

is recommended. The majority of GC patients in clinical practice have

advanced or metastatic disease, where chemotherapy is considered

standard treatment, to provide palliation and prolong survival; however,

prognosis remains poor. This paper reviews chemotherapy and targeted

therapies for GC, focusing on trastuzumab.

Key Words: Gastric Cancer, HER2, Trastuzumab

Introduction

Gastric cancer (GC) treatment and prognosis vary in different regions

of the world; incidence of the disease, approach to early diagnosis and

treatment varies greatly between western and the eastern hemispheres.

It is the second leading cause of cancer-related death worldwide (1).

In the US, it was estimated there would be 21,500 new cases and

10,880 deaths from GC in 2008; whereas more than 100,000 new

cases are diagnosed and 50,000 die annually of this cancer in Japan.

Approximately 50% of GC cases in Japan are diagnosed at an early

stage, with 5-year survival for stage I GC reported above 90%. In

the Western world only 27% of cases are diagnosed at early stage

and 5-year survival for stage II-III disease is 20-50%, and 5-10% for

stage IV. Different strategies have been tested around the world and

have resulted in different approaches for localized and advanced GC

as summarized in Figure 1.

Chemotherapy for GC

Locoregional and distant recurrences are frequently seen after surgery

for GC, therefore, different approaches as adjuvant and perioperative

therapies have been tested. Three strategies have successfully

demonstrated a survival benefit compared with surgery alone.

Postoperative administration of 5-fluorouracil (5FU) and leucovorin, in

combination with external beam radiation therapy, is routinely used

in the US (2). Perioperative chemotherapy with a combination of

epirubicin, cisplatin and 5FU (ECF), is becoming standard practice

in many countries for resectable GC patients (3). In Japan, adjuvant

monotherapy with surgery + adjuvant chemotherapy (S-1) (Fig. 1) is

common practice (4).

Chemotherapy for advanced unresectable or recurrent GC, in selected

fit patients, offers significant advantages, such as increased survival,

Trastuzumab