A 19-year-old black woman presented to the ER with worsening nausea,
vomiting and abdominal pain for the last few days. On examination, she had
generalized abdominal tenderness. Several investigations, including blood tests
and CT scan of the abdomen and pelvis, indicated inflammatory bowel disease,
and she was treated conservatively without significant improvement. Eventually,
she proceeded to the operating room for an exploratory laparotomy with an
anticipation of bowel obstruction secondary to adhesions.
To everyones surprise, the patient was found to have multiple
dilated small bowel loops, and both the entire cecum and ascending colon were
heavily involved with a neoplastic process that was difficult to characterize.
Due to this infiltrative process, the patient underwent resection of her
terminal ileum, the entire ascending colon, and transverse colon to relieve the
Unresectable tumor implants were noted on the mesentery of the small
bowel. Pathology showed a poorly differentiated adenocarcinoma with signet ring
cell features. She recovered well after surgery and underwent an upper
endoscopy that showed edematous, friable, loss of normal gastric folds and
ulcerated gastric mucosa involving the entire stomach sparing the pylorus and
part of the antrum. The biopsy showed adenocarcinoma with signet ring cell
Gastric cancer is the second most common cause of cancer-related death
in the world. Many Asian countries, including Korea, China, Taiwan and Japan,
have very high rates of gastric cancer, as opposed to the incidence of gastric
cancer in the United States, which has declined dramatically since the 1930s.
Approximately 21,500 patients are diagnosed annually, and 10,880 are expected
to die from this disease.
Prognosis has improved only marginally over the last two decades despite
the declining incidence and significant advances in surgical therapy and
postoperative care. The overall five-year survival rate for all stages combined
was 24% between 1996 and 2003, compared to 15% between 1975 and 1977.
Until the early 1990s, active chemotherapeutic agents in advanced
gastric cancer were bleomycin, mitomycin-C, methotrexate, 5-FU, etoposide,
cisplatin and doxorubicin. All were associated with modest response rates of
short duration. Combination chemotherapy revealed higher response rates in
phase-2 trials, but randomized trials had lower response rates. The combination
of cisplatin and 5-FU (CF) was the most commonly used regimen in the setting of
metastatic gastric and esophageal cancer. The response rate of this regimen, as
depicted by a randomized phase-2 trial, was 35%, but one-year survival was not
much different than single-agent cisplatin.
Recent studies have compared the addition of docetaxel (Taxotere, Sanofi
Aventis) to cisplatin-based regimens. The final results of the TAX 325 Study,
which compared DCF (docetaxel, cisplatin and 5-FU) to CF were reported in 2005
and published in 2007. Response rate was 37% vs. 25%, progression free survival
was 5.6 months vs. 3.7 months, and overall survival was 10.5 months vs. 9.6
months (all in favor of DCF). The two-year survivals were 18% vs. 9% (in favor
of DCF). This was the highest reported two-year overall survival in gastric
cancer at the time. Toxicities for both regimens were substantial but
The use of other regimens such as ECF (epirubicin, cisplatin, 5-FU) has
shown promise in advanced disease, but that regimen has potential cardiac risk,
and reported overall survival is only eight to nine months. Also, the previous
regimens included cisplatin with bolus 5-FU, but the ECF regimen has infusional
5-FU, which may have affected the better response rate. Therefore, the benefit
of adding epirubicin to the CF regimen remains unknown.
There are multiple trials still ongoing for this indication, and several
new abstracts were presented in ASCO 2008. One of them was by Enzinger et al
who reported that bevacizumab (Avastin, Genentech), cisplatin, docetaxel and
irinotecan in a three-week cycle produced a response rate of 63% in metastatic
esophageal/gastric cancer. Another abstract by Han et al showed the outcome of
using cetuximab (Erbitux, ImClone) in combination with FOLFOX6. The response
rate was 50%, with 5.5 months time to progression and 9.9 months overall
survival. Randomized trials are needed to confirm these results.
Approximately 25% of metastatic gastric cancers over express
HER2. It is more common with intestinal type gastric cancers than
with diffuse type. Recently, the results of phase-3 ToGA trial showed
significantly higher response rates in patients with
HER2over-expressing tumors when treated with CF and
trastuzumab (Herceptin, Genentech; 47% vs. 35%). These are the preliminary
results; however, I think it is reasonable to screen metastatic gastric cancer
patients for HER2 over expression.
The above mentioned patient was started on chemotherapy with DCF and
HER2 status to date is pending.
Wajeeha Razaq, MD, is an Assistant Professor of Medicine at the
University of Nebraska, Omaha.
For more information:
- Bleiberg H. Eur J Cancer. 1997;33:1216-1220.)
- Van Cutsem E. #LBA4509. Presented at: 2009 ASCO Annual Meeting; May
29-June 2, 2009; Orlando.
- Van Cutsem E. J Clin Oncol. 2006.;24:4991-4997.