Gastric cancer, also known as stomach cancer, begins when cells in the stomach start to grow uncontrollably. For some forms of this cancer, a specific chemotherapy regimen called FLOT is frequently used. This regimen is a combination of several medications designed to combat cancer cells effectively.
Understanding the FLOT Regimen
The FLOT regimen is a combination of four distinct chemotherapy drugs. The “F” in FLOT stands for Fluorouracil, an antimetabolite drug. This medication interferes with the genetic material (DNA and RNA) inside cancer cells, preventing them from growing and dividing.
The “L” represents Leucovorin, a folate analog. Leucovorin enhances the effectiveness of Fluorouracil by stabilizing its binding to an enzyme within cancer cells, thereby increasing its ability to kill these cells. This synergistic action makes Fluorouracil more potent in the regimen.
Oxaliplatin (O) is a platinum-based chemotherapy drug. It works by forming cross-links in the DNA of cancer cells, which damages their genetic code and prevents them from replicating. This DNA damage ultimately leads to the death of the cancer cells.
Finally, “T” stands for Docetaxel, a taxane-class chemotherapy drug. Docetaxel disrupts the internal structure of cancer cells, targeting microtubules necessary for cell division. By interfering with these structures, Docetaxel stops cancer cells from dividing and growing.
The FLOT Treatment Process
FLOT chemotherapy is typically administered as “perioperative” treatment, meaning it is given both before and after surgery. The initial phase, neoadjuvant chemotherapy, aims to shrink the tumor before surgical removal. This approach can make the surgery more successful by reducing tumor size and potentially targeting microscopic cancer cells that may have spread.
Following the neoadjuvant phase and subsequent surgery, patients usually receive adjuvant chemotherapy. This post-operative treatment helps eliminate any remaining cancer cells, reducing the risk of the cancer returning in the future.
A standard FLOT treatment cycle involves administering the drugs intravenously, typically over several hours, once every two weeks. Patients usually receive four cycles of FLOT before surgery and another four cycles after surgery, totaling eight cycles over several months. These infusions are generally given in an outpatient clinic or hospital setting.
Potential Side Effects
Undergoing FLOT chemotherapy can lead to a range of side effects. Gastrointestinal issues are common, including nausea and vomiting, which can be managed with anti-nausea medications prescribed by the oncologist. Diarrhea is also a frequent side effect, requiring careful monitoring and management to prevent dehydration.
Many patients experience fatigue, a pervasive tiredness that is not relieved by rest. Peripheral neuropathy is another notable side effect, characterized by tingling, numbness, or pain, especially in the hands and feet, due to nerve damage caused by some of the drugs. This sensation can sometimes be permanent, so careful monitoring is needed.
Changes in taste are also common, making food less appealing or causing a metallic taste in the mouth. Mouth sores, known as mucositis, can develop in the lining of the mouth and throat, making eating and swallowing painful. Hair thinning or loss can occur, though hair usually regrows after treatment concludes.
Furthermore, chemotherapy can lower blood cell counts, a condition called myelosuppression. A decrease in white blood cells (neutropenia) increases the risk of infection, while a reduction in red blood cells (anemia) can lead to increased fatigue. Lowered platelet counts (thrombocytopenia) can increase the risk of bleeding. Oncologists employ various supportive care strategies to help manage these side effects and improve patient comfort throughout the treatment course.
Efficacy and Outcomes
FLOT has become a standard treatment for patients with locally advanced, resectable gastric or gastroesophageal junction cancer. This regimen is particularly effective for cancers that have grown into the stomach wall or nearby lymph nodes but have not spread to distant organs. Its use is based on strong clinical evidence demonstrating superior outcomes compared to older regimens.
The FLOT4 clinical trial compared FLOT to an older regimen called ECF/ECX (Epirubicin, Cisplatin, and Fluorouracil/Capecitabine). The trial demonstrated that patients treated with FLOT experienced significantly improved overall survival, meaning they lived longer on average. This finding established FLOT as a preferred first-line treatment option.
The trial also showed that FLOT led to better tumor shrinkage before surgery, which increases the likelihood of a complete surgical removal of the cancer. A higher percentage of patients achieved a pathological complete response, meaning no cancer cells were found in the surgical specimen after neoadjuvant FLOT. These improved pathological response rates and survival benefits highlight FLOT’s effectiveness.