Patient With Advanced Gastric Cancer Responds Twice to the Same Systemic Therapy

Gastric cancer is the world’s second leading cause of cancer death (after skin cancer) and the 14th most common malignancy in the United States.^1,2 It is the 8th most common cause of cancer mortality in the United States with over 20,000 new cases diagnosed annually.³ Certain regions of the world, such as Japan and Korea, have gastric cancer rates as high as 80 per 100,000 population. In the West, nearly 50% of all gastric cancers are located at the cardia; this represents an approximately sixfold increase over the past 3 decades.⁴

Risk factors for gastric cancer include Helicobacter pylori infection, tobacco use, obesity, chronic gastritis, pernicious anemia, a history of partial gastric resection more than 15 years previously, and family history including hereditary diffuse gastric cancer (HDGC), hereditary nonpolyposis colorectal cancer (HNPCC), and familial adenomatous polyposis.

Symptoms of gastric cancer include dyspepsia, vague epigastric pain, anorexia, nausea, vomiting, fatigue, early satiety, anemia, bleeding, and weight loss. Sometimes, the presenting symptoms are those caused by metastases.

Advanced gastric cancer is an incurable condition, with a median survival of ≤ 9 months.¹ Treatment for metastatic gastric cancer is palliative only. Cytotoxic agents in the following classes have activity against gastric adenocarcinoma: taxane, platinum compounds, flouropyrimidines, camptothecins, anthracyclines, alkylating agents, and topoisomerase II inhibitors. Level-I evidence for extending overall survival exists only for docetaxel⁵ and cisplatin.⁶ We present a report of a patient who experienced prolonged control of his advanced gastric adenocarcinoma whose disease subsequently responded to treatment with the same systemic combination.

CASE REPORT

A 33 year-old white man, who had a past medical history of H. pylori infection, was seen at the University of Texas M. D. Anderson Cancer Center (UTMDACC) in October of 2005 with a new diagnosis of localized gastric adenocarcinoma. Symptoms of mid epigastric pain began in early 2004. The patient smoked lightly, drank socially, and admitted he occasionally used illicit drugs. His maternal uncle had gastric cancer and other relatives had other cancers. Results of a test for H. pylori infection were positive and he was treated with anti-biotics. The patient’s symptoms resolved for approximately 12 months, after which similar symptoms re-emerged along with anorexia and weight loss on the order of 4 kg.

The patient underwent upper endoscopy, which revealed the presence of atypical cells only as well as evidence of recurrent H. pylori infection. He was again treated with antibiotics. In September of 2005, the patient underwent repeat endoscopy, which revealed a hard, superficial, granular lesion covering most of the fundus. Biopsy revealed a poorly differentiated adenocarcinoma with focal signet ring cell features. Computed tomography (CT) studies revealed no metastases. The patient underwent an endoscopic ultrasonography, laparoscopy, and positron emission tomography (PET) studies, among other tests, at UTMDACC. Endoscopy showed an ulcerated proximal gastric cancer (Figure 1) that was T3N+ by ultrasonography (Figure 2A and 2B). There was no evidence of M+ cancer, but computed tomography did reveal gastric wall thickening with nodal involvement (Figure 3). The PET scans revealed an avid primary and nodes.

Figure 1.

Endoscopic evidence of a polypoid and deeply ulcerated gastric carcinoma observed in the proximal stomach.

Figure 2A.

Radial endosonography showing a hypoechoic tumor process extending beyond the musularis propria layer into the serosa. Abbreviations: MP = muscularis propria; T = tumor

Figure 2B.

A hypoechoic tumor process is extending beyond the muscularis propria layer into the serosa. A nearly round hypoechoic lymph node with regular border is seen in the left gastric region.

Abbreviations: MP = muscularis propria; LN = lymph node

Figure 3.

Computed tomography of the abdomen showing gastric wall thickening and gastrohepatic lymphadenopathy.

Upon completion of the workup, the patient was treated on a preoperative protocol that included induction chemotherapy with 5-fluorouracil and oxaliplatin followed by chemoradiotherapy with the same agents. The preoperative work-up demonstrated improvement in the primary area, no metastatic cancer, and a healed malignant ulcer with no cancer seen in the biopsy specimen obtained by repeat endoscopy. In April of 2006, he underwent exploratory surgery with the intention to perform a D2 dissection. Upon exploration, however, a diagnosis of low-volume peritoneal adenocarcinoma was made. Gastrectomy was not performed. The patient recovered and in late May of 2006, PET revealed evidence of diffuse peritoneal involvement and pulmonary metastases.

The patient was started on therapy with docetaxel (40 mg/m² every 2 weeks), capecitabine (1,500 mg/m²/day 7 days on, 7 days off), and bevacizumab (5 mg/kg) every 2 weeks. In August of 2006, PET showed improvement. He continued therapy with excellent tolerance and a PET scan in January of 2007 showed complete clinical remission. Also, an endoscopic evaluation showed no cancer. The patient was given a treatment break and he returned for followups in April 2007, July 2007, and November 2007—he maintained complete clinical remission as well as an excellent quality of life.

In January of 2008, the patient developed abdominal symptoms suggestive of bowel obstruction. Abdominal exploration was performed at another hospital and he underwent small-bowel resection (peritoneal metastases were again documented). He remained under observation, as postoperative PET showed no obvious cancer that could be followed for treatment response evaluation. In July of 2008, his PET revealed a new left supraclavicular adenopathy and increasing peritoneal disease (Figure 4A). Therapy was initiated once again with docetaxel, bevacizumab, and capecitabine.

Figure 4A.

Positron emission tomography showing left supraclavicular malignant nodes.

A PET scan performed toward the end of August 2008 showed a complete metabolic response (Figure 4B). This time, however, the remission did not last long, and by November of 2008 there was evidence of cancer progression. He was treated with irinotecan and cetuximab but soon became jaundiced. In March of 2009, there was considerable progression of his cancer (Figure 5) and marked deterioration of his general condition. The patient died of his disease in April of 2009, approximately 4.5 years after his diagnosis.

Figure 4B.

Positron emission tomography showing resolution of the left supraclavicular nodes.

Figure 5.

Positron emission tomography showing extensive abdominal cancer and a draining biliary tube.

DISCUSSION

This case is highly unusual, and it illustrates a number of points worthy of consideration. (1) Clinical biology of gastric cancer can be quite heterogeneous and dramatic, and a prolonged remission in response to therapy is possible. (2) It is possible to achieve remission again (albeit it was not as long as it was the first time) provided a treatment-free interval has elapsed. (3) Permitting a treatment break after a stable response is achieved (in this case a complete clinical response) may be desirable in select patients as it can result in a prolonged treatment-free interval with good quality of life. (The treatment-free interval in this case was approximately 12 months.)

For patients with metastatic gastroesophageal cancer, the 2- year survival rates remain under 20%⁵ and better therapies are needed to improve outcomes. Fortunately, many phase III randomized trials are now ongoing (www.clinicaltrials.gov/).