What are the most common side effects of FLOT (Fluorouracil, Leucovorin, Oxaliplatin, Docetaxel) chemotherapy agents?

From the Guidelines

FLOT chemotherapy is associated with significant side effects, including neutropenia, peripheral neuropathy, gastrointestinal issues, mucositis, fatigue, and alopecia, as reported in recent studies 1. The most frequent side effects of FLOT chemotherapy include:

• Neutropenia (low white blood cell count), which increases infection risk
• Peripheral neuropathy from oxaliplatin, causing tingling and numbness in hands and feet
• Gastrointestinal issues like nausea, vomiting, and diarrhea
• Mucositis (mouth sores)
• Fatigue
• Alopecia (hair loss) Patients may also experience hand-foot syndrome from 5-FU, causing redness, swelling, and pain in palms and soles. Oxaliplatin specifically can trigger cold sensitivity, where exposure to cold temperatures causes painful sensations. Docetaxel may cause fluid retention and nail changes. These side effects occur because chemotherapy drugs target rapidly dividing cells, affecting not only cancer cells but also normal cells with high turnover rates like those in bone marrow, digestive tract, and hair follicles. Management typically includes prophylactic medications for nausea, close monitoring of blood counts, and dose adjustments as needed to balance treatment efficacy with quality of life, as suggested by recent guidelines 1. The evidence from the 2019 study 1 provides the most recent and highest quality data on the side effects of oxaliplatin-containing chemotherapy regimens, including FLOT. The study reports that the most common adverse events associated with FLOT chemotherapy include peripheral sensory neurotoxicity, diarrhea, febrile neutropenia, neutropenia, thrombocytopenia, nausea, vomiting, mucositis, fatigue, and hand-foot syndrome. Overall, the side effects of FLOT chemotherapy can be significant, and careful management is necessary to minimize their impact on patients' quality of life.

From the FDA Drug Label

Clinically relevant adverse reactions in greater than or equal to 2% and less than 5% of the patients in the oxaliplatin and fluorouracil/leucovorin combination arm (listed in decreasing order of frequency) were: anxiety, myalgia, erythematous rash, increased sweating, conjunctivitis, weight decrease, dry mouth, rectal hemorrhage, depression, ataxia, ascites, hemorrhoids, muscle weakness, nervousness, tachycardia, abnormal micturition frequency, dry skin, pruritus, hemoptysis, purpura, vaginal hemorrhage, melena, somnolence, pneumonia, proctitis, involuntary muscle contractions, intestinal obstruction, gingivitis, tenesmus, hot flashes, enlarged abdomen, and urinary incontinence Table 13: Laboratory-Related Adverse Reactions Occurring in ≥5% of Patients with Previously Treated Advanced Colorectal Cancer

• Alanine transaminase † Aspartate transaminase Laboratory-Related Adverse ReactionOxaliplatin and FU/LV N=150Oxaliplatin N=153FU/LV N=142 All Grades (%)Grades 3 to 4 (%)All Grades (%)Grades 3 to 4 (%)All Grades (%)Grades 3 to 4 (%) Hematology Anemia812641682 Leukopenia7619130341 Neutropenia734470255 Thrombocytopenia644303200 Hepatic Increased ALT*310361283 Increased AST†470544392 Increased Bilirubin131135226

The most common side effects of FLOT (Fluorouracil, Leucovorin, Oxaliplatin) chemotherapy agents are:

• Hematologic reactions:
  • Anemia
  • Leukopenia
  • Neutropenia
  • Thrombocytopenia
• Hepatic reactions:
  • Increased ALT
  • Increased AST
  • Increased Bilirubin
• Other reactions:
  • Anxiety
  • Myalgia
  • Erythematous rash
  • Increased sweating
  • Conjunctivitis
  • Weight decrease
  • Dry mouth
  • Rectal hemorrhage
  • Depression
  • Ataxia
  • Ascites
  • Hemorrhoids
  • Muscle weakness
  • Nervousness
  • Tachycardia
  • Abnormal micturition frequency
  • Dry skin
  • Pruritus
  • Hemoptysis
  • Purpura
  • Vaginal hemorrhage
  • Melena
  • Somnolence
  • Pneumonia
  • Proctitis
  • Involuntary muscle contractions
  • Intestinal obstruction
  • Gingivitis
  • Tenesmus
  • Hot flashes
  • Enlarged abdomen
  • Urinary incontinence 2

From the Research

Common Side Effects of FLOT Chemotherapy Agents

The FLOT chemotherapy regimen, which consists of Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel, has been associated with several common side effects, including:

• Diarrhea 3, 4, 5
• Leucovorin and neutropenia (including severe cases) 3, 4, 5
• Infections (including severe cases) 3
• Peripheral neuropathy 3, 6, 7
• Fatigue 4
• Nausea and vomiting 4, 5, 7
• Anemia 3, 5
• Thrombocytopenia 6, 7
• Hemolytic anemia and pancytopenia (less common) 6

Severe Side Effects

Severe side effects associated with the FLOT regimen include:

• Severe neutropenia 3, 4, 5
• Severe infections 3
• Severe diarrhea 4
• Severe nausea and vomiting 3
• Severe anemia 3
• Thromboembolic events 3
• Immune-mediated cytopenias (such as thrombocytopenia, hemolytic anemia, and pancytopenia) 6

Management of Side Effects

Management of side effects associated with the FLOT regimen is crucial to minimize their impact on patients. This includes:

• Monitoring of complete blood counts to detect hematologic toxicity 6, 7
• Use of antiemetics to control nausea and vomiting 7
• Management of diarrhea and other gastrointestinal side effects 4, 7
• Monitoring for signs of neurotoxicity and adjusting treatment accordingly 7