Gastric cancer, which begins in the stomach, presents a serious health challenge. This disease often necessitates aggressive treatment approaches to manage its progression. Chemotherapy is a widely used method to combat gastric cancer by destroying cancer cells or slowing their growth. Among various chemotherapy regimens, FLOT has emerged as an important multi-drug treatment. This combination regimen is frequently employed for gastric and gastroesophageal junction adenocarcinomas.
Understanding FLOT Chemotherapy
FLOT is a combination chemotherapy regimen named after its four component drugs: 5-fluorouracil (5-FU), Leucovorin, Oxaliplatin, and Docetaxel. This regimen is administered in both neoadjuvant and adjuvant settings for gastric and gastroesophageal junction adenocarcinoma. Neoadjuvant treatment occurs before surgery to shrink tumors, potentially making them easier to remove. Adjuvant therapy is given after surgery to eliminate any remaining cancer cells and reduce the likelihood of recurrence.
How FLOT Targets Gastric Cancer
Each drug within the FLOT regimen targets cancer cells through distinct mechanisms, enhancing the anti-cancer effect.
Docetaxel, a taxane, interferes with the normal function of microtubules, essential structures for cell division. By stabilizing microtubules and preventing their disassembly, Docetaxel halts cell division and induces programmed cell death.
Oxaliplatin, a platinum-based compound, exerts its effects by damaging DNA within cancer cells. It forms cross-links in DNA strands, which prevents DNA replication and transcription, leading to cell death. This DNA damage disrupts the processes necessary for cancer cell growth and survival.
5-Fluorouracil (5-FU) is an antimetabolite that disrupts the synthesis of DNA and RNA. It interferes with the enzyme thymidylate synthase, necessary for DNA production, leading to a shortage of a DNA building block and cell death. 5-FU metabolites can also be incorporated into the cell’s RNA and DNA, impairing their function.
Leucovorin, also known as folinic acid, enhances 5-FU’s effectiveness. It stabilizes the binding of an active metabolite of 5-FU to thymidylate synthase, intensifying 5-FU’s inhibitory effect on DNA synthesis. This synergistic action allows 5-FU to work more efficiently.
Administering FLOT and Managing Side Effects
FLOT chemotherapy is administered intravenously in cycles over several months. A common schedule involves 8 cycles, each lasting 14 days, with surgery usually occurring after the fourth cycle. Patients receive steroid tablets for three days, starting the day before chemotherapy, to help prevent side effects.
Common side effects include:
Nausea
Vomiting
Fatigue
Hair loss
Diarrhea
Low blood counts (neutropenia, which can increase infection risk)
Peripheral neuropathy (tingling or numbness in the hands and feet), linked to oxaliplatin.
These side effects arise because chemotherapy drugs target rapidly dividing cells, affecting not only cancer cells but also healthy cells with high turnover rates, such as those in bone marrow, the digestive tract, and hair follicles.
More serious, less common side effects include severe neutropenia, fluid retention, or allergic reactions. Patients are closely monitored, and medical professionals provide supportive medications, such as antiemetics for nausea, and may adjust dosages or delay treatment if side effects become severe. Prompt reporting of any new or worsening symptoms to the healthcare team is advised.
Effectiveness and Patient Outlook
FLOT chemotherapy has demonstrated significant effectiveness in improving outcomes for patients with gastric and gastroesophageal junction adenocarcinoma. This regimen can shrink tumors, facilitating more successful surgical removal. Studies indicate that FLOT can lead to improved disease-free survival and overall survival rates compared to older chemotherapy regimens. For instance, one study reported a median overall survival of 50 months with FLOT, compared to 35 months with a different regimen.
Patient selection for FLOT considers overall health and cancer stage, as patients must be healthy enough to tolerate the intensive regimen. The regimen has shown a higher pathological response rate, meaning a greater reduction in cancer cells observed in removed tissues. The benefits of FLOT are most pronounced when patients complete the full perioperative regimen, including cycles both before and after surgery. A multidisciplinary approach, involving various medical specialists, is important for optimizing treatment plans and patient management.