Gastric cancer and cancer of the gastroesophageal junction require powerful systemic treatment. For locally advanced, resectable cancers, a comprehensive approach is necessary. Chemotherapy is used to shrink the tumor before surgery and eliminate any remaining microscopic disease afterward. This strategy improves the chances for a successful surgical outcome and long-term survival.
Defining the FLOT Regimen
The FLOT regimen is a combination chemotherapy protocol named after the four agents it includes: Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel. Each drug works through a different mechanism to attack rapidly dividing cancer cells, creating a synergistic effect. Fluorouracil is an antimetabolite that disrupts the production of DNA and RNA, preventing cell division.
Leucovorin (folinic acid) is not a chemotherapy agent itself but enhances the effectiveness of Fluorouracil. Oxaliplatin is a platinum-based compound that creates cross-links in the cancer cell’s DNA, leading to cell death. Docetaxel belongs to the taxane class of drugs, which interferes with the internal cellular structure necessary for cells to divide.
Clinical Application for Gastric Cancer
FLOT is the established standard of care for patients with locally advanced, resectable adenocarcinoma of the stomach or gastroesophageal junction. It is administered in a perioperative setting, meaning treatment is given both before and after surgery. The pre-operative therapy, known as neoadjuvant treatment, aims to shrink the tumor for easier and more complete removal.
The superiority of FLOT was demonstrated in the FLOT4 trial, which compared it to older standard regimens. Patients receiving FLOT experienced better long-term survival rates. This intensive four-drug combination increases the likelihood of successful surgical resection.
Understanding the Treatment Schedule
The FLOT regimen is delivered in cycles, with each cycle lasting 14 days. Treatment typically involves a total of eight cycles, divided equally between the pre-surgery and post-surgery phases. Patients receive the Docetaxel, Oxaliplatin, and Leucovorin infusions on Day 1 of each cycle in the clinic.
The Fluorouracil component is administered as a continuous infusion, often over 24 hours, using a small, portable pump the patient takes home. The pump is disconnected the following day, followed by a nearly two-week rest period before the next cycle begins. Surgery is generally scheduled about four weeks after the completion of the fourth pre-operative cycle.
Common Side Effects and Management
Patients should anticipate several common side effects, which are managed proactively by the care team. Neutropenia, a drop in white blood cells, is a frequent concern managed with growth-factor injections. Patients must monitor for fever, which signals a serious infection requiring immediate medical attention.
Peripheral neuropathy, causing numbness or tingling in the hands and feet, is primarily linked to Oxaliplatin. This drug can also trigger a temporary, painful sensitivity to cold. Gastrointestinal side effects like nausea, vomiting, and diarrhea are common but are often well-controlled with anti-sickness medications. Other side effects include mucositis (mouth sores) and significant fatigue.
Anticipated Treatment Outcomes
The FLOT regimen has improved outcomes for patients with resectable gastric and gastroesophageal junction cancer compared to older protocols. The FLOT4 trial demonstrated an improvement in median overall survival time to 50 months, compared to 35 months previously. This translates to an estimated nine percent increase in the five-year overall survival rate.
A major goal of pre-operative treatment is achieving a significant pathological response, meaning cancer cells are destroyed or reduced in the surgical specimen. FLOT achieves a pathological complete response (no viable cancer cells found) in approximately 16 to 30 percent of patients. This high rate of tumor destruction before surgery indicates successful local disease control and is associated with better long-term survival.