Preoperative FOLFOX Therapy Safe, Efficacious for Esophageal Cancer

Esophageal cancer
Researchers assessed the safety and short-term efficacy of FOLFOX therapy in patients with esophageal cancer who were ineligible for cisplatin-containing treatment.

In individuals who cannot receive cisplatin-containing regimens, chemotherapy containing leucovorin, 5-fluorouracil, and oxaliplatin (FOLFOX) is a safe and efficacious preoperative treatment in the short term for resectable locally advanced esophageal squamous cell carcinoma (LAESCC), according to study findings in Esophagus.

Researchers conducted a retrospective study at the National Cancer Center Hospital in Japan, from 2019 to 2021, to assess the effects of FOLFOX therapy in patients with resectable LAESCC who are ineligible for cisplatin-containing treatments. Eligibility criteria included:

  • histologically confirmed esophageal squamous cell carcinoma;
  • cT1N1-3M0, cT2-3N0-3M0, or cT1-3N0-3M1;
  • renal dysfunction (creatinine clearance <60 mL/min);
  • cardiac dysfunction (ejection fraction ≤50% on cardiac ultrasound, poorly controlled arrhythmia, or previous heart failure);
  • age 75 years and older.

Patients received FOLFOX therapy intravenously every 2 weeks for 3 or 4 cycles, followed by surgery. The FOLFOX treatment consisted of oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, and a bolus of 5-fluorouracil 400 mg/m2 on day 1 followed by 5-fluorouracil 2400 mg/m2 over 46 hours. Of 44 patients identified, researchers included 35 for the study.

Study participants had a median age of 77 (range, 65-89) years, 71.4% were men, 74.3% had renal dysfunction, and 17.1% had cardiac dysfunction.

Primary outcomes included adverse events during preoperative treatment and hisopathological response.

After 1 treatment cycle, 3 patients discontinued the study due to progression of disease or neutropenia, and another patient discontinued after the second cycle due to disease progression. After treatment cycle 3, the 31 remaining patients underwent esophagectomy. Patients experienced postsurgical complications, including pneumonia (35.5%), nerve paralysis (25.8%), and anastomotic leakage (16.1%).

The most common adverse events were neutropenia (60%) and leucopenia (28.6%). There were neither treatment-related deaths for preoperative chemotherapy nor operation-related deaths for esophagectomy.

A total of 27 patients who received an esophagectomy had a complete resection of their tumor.

Of the 6 patients who had measurable target lesions, 1 showed complete clinical response to FOLFOX therapy, 2 showed a partial response, 1 had stable disease, and 1 showed disease progression. The objective response rate was 50%.

Study limitations include the single-center design, allowing the treatment strategy to be decided at the discretion of each oncologist, and a short follow-up.

“Patients with resectable LAESCC who were not eligible for CDDP showed a favorable histopathological response to preoperative FOLFOX therapy,” the study authors noted. “Although there was a high frequency of severe neutropenia, nonhematological adverse events were mild. In particular, any renal or gastrointestinal toxicity was tolerable.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Kadono T, Yamamoto S, Hirose T, et al. Safety and short‐term efficacy of preoperative FOLFOX therapy in patients with resectable esophageal squamous cell carcinoma who are ineligible for cisplatin. Esophagus. Published online September 1, 2022. doi:10.1007/s10388-022-00951-4