What is the best initial chemotherapy regimen for stomach cancer?

Stomach cancer is among the 5 most common cancer types in our country as worldwide, and substantially shortens survival when detected at an advanced stage. Because of its nature, by diagnosis the disease has usually either advanced locally or spread to other organs (metastasized). In our country, nearly three quarters of all stomach cancers are diagnosed at this stage, meaning the metastatic stage.

Treating locally advanced or metastatic stomach cancer is extremely challenging. Looking at the last 20-30 years, we have not moved beyond a few basic drugs. After the 2000s, as with breast cancer, we found that some stomach cancers carry a specific cell surface receptor called Her2. These Her2-positive stomach cancers constitute approximately %20 of all stomach cancers.

When we encounter stomach cancer that cannot be operated on because it is locally advanced or metastatic, we must determine whether there is an opportunity for targeted therapy, known as a smart drug, associated with Her2 positivity. If it is Her2-positive, a chemotherapy regimen now well recognized and known to prolong life is used.

The chemotherapy regimen consists of 3 drugs:

1. Cisplatin, a platinum analogue known for many years,
2. 5-fluorouracil (5FU), and 
3. The smart drug containing trastuzumab, known worldwide as Herceptin, which targets Her2

Based on studies to date, particularly over the last 5 years, the use of Herceptin in Her2-positive stomach cancer has become standard.

For %80 of stomach cancers, which are Her2-negative, there is debate about the most appropriate treatment

Cisplatin and 5-fluorouracil have been used to treat stomach cancer for many years. Adding docetaxel, a drug in the taxane category, to these two agents has made substantial contributions to the lives of Her2-negative patients, who constitute most stomach cancers. However, this triple treatment (Docetaxel+Cisplatin+5FU = DCF) has troubled physicians because of side effects, made patient management difficult and reduced patients' quality of life. In this confusing situation, using the triple chemotherapy regimen over shorter periods at lower doses was termed modified DCF and introduced new treatment applications. Studies over the past few years have shown that giving this triple treatment over shorter periods, at frequent intervals and lower doses causes fewer side effects.

The January 2015 issue of the respected oncology journal Gastric Cancer closely examined this controversial subject. The comparative study compared the conventional stomach cancer treatment, the cisplatin-5FU double chemotherapy regimen,with a treatment shown not to severely impair quality of life, given at a lower dose, not every 3 weeks but every 14 days, the triple chemotherapy regimen (modified DCF) .

We believe the result surprised even the researchers. Compared with conventional chemotherapy, the reduced-dose triple combination given every 14 days markedly prolonged survival.

This result can guide the oncology community, particularly in this difficult treatment decision. However, closer examination raised a question because not all patients receiving modified DCF had stage 4 disease: approximately a third had locally advanced disease. Nevertheless, this did not overshadow the study's final success.

From now on, our strategy for patients with stomach cancer inoperable because of metastasis or local advancement will be to begin treatment with the chemotherapy regimen called modified DCF, which is known to prolong survival and has fewer side effects. However, it should not be forgotten that the Her2 receptor level must be assessed in stomach cancer patients for individualized treatment.