From the Guidelines
Neoadjuvant chemotherapy for esophageal cancer should typically involve a combination of platinum-based agents and fluoropyrimidines, with the most common regimen being CROSS, which combines carboplatin and paclitaxel given weekly for 5 weeks with concurrent radiotherapy. The choice of neoadjuvant chemotherapy regimen for esophageal cancer depends on various factors, including the patient's performance status, comorbidities, and tumor histology. Some of the key regimens used in the treatment of esophageal cancer include:
- CROSS: combines carboplatin (AUC 2 mg/mL/min) and paclitaxel (50 mg/m²) given weekly for 5 weeks with concurrent radiotherapy (41.4 Gy in 23 fractions) 1
- FLOT: consists of docetaxel (50 mg/m²), oxaliplatin (85 mg/m²), leucovorin (200 mg/m²), and 5-fluorouracil (2600 mg/m² as 24-hour infusion) given every 2 weeks for 4 cycles before surgery
- ECF/ECX: includes epirubicin (50 mg/m²), cisplatin (60 mg/m²), and 5-FU (200 mg/m²/day or capecitabine 625 mg/m² twice daily) for 3 cycles
- Cisplatin (75-100 mg/m²) plus 5-FU (750-1000 mg/m²/day for 4-5 days) every 3-4 weeks for 2-3 cycles These regimens aim to downstage tumors before surgery, increase R0 resection rates, and eliminate micrometastases. Treatment selection depends on patient factors, including performance status, comorbidities, and tumor histology, with squamous cell carcinomas often showing better response to chemoradiation and adenocarcinomas sometimes treated with perioperative chemotherapy approaches 1. The most recent and highest quality study, published in 2022, supports the use of neoadjuvant chemoradiotherapy in the treatment of esophageal cancer, with the CROSS regimen being a standard of care 1.
From the Research
Neoadjuvant Chemotherapy Protocols for Esophageal Cancer
The neoadjuvant chemotherapy protocols for esophageal cancer vary, but common regimens include:
- Cisplatin/5-fluorouracil (5-FU) 2, 3, 4, 5
- Carboplatin/paclitaxel 2, 3, 5
- Docetaxel, cisplatin, and 5-fluorouracil (DCF) or modified DCF (mDCF) 6
Efficacy of Neoadjuvant Chemotherapy Regimens
Studies have compared the efficacy of these regimens, with results including:
- Cisplatin/5-FU was associated with higher rates of pathologic complete response and improved recurrence-free and overall survival compared to carboplatin/paclitaxel in one study 2
- Carboplatin/paclitaxel was associated with better survival outcomes, higher surgical resection rates, and better safety profiles than cisplatin/5-FU in another study 3
- mDCF had an acceptable toxicity profile and disease-free survival (DFS) and overall survival (OS) outcomes in a community setting 6
- Docetaxel/cisplatin (DP) resulted in better overall survival (OS) and progression-free survival (PFS) compared to cisplatin/5-FU (PF) in patients with unresectable esophageal squamous cell carcinoma (ESCC) 4
Toxicity and Tolerability
Toxicity and tolerability profiles of the regimens include:
- Cisplatin/5-FU was associated with a higher incidence of non-hematological severe adverse events (sAE) compared to carboplatin/paclitaxel 3
- Carboplatin/paclitaxel was associated with decreased weight loss and improved pathologic response for trimodality patients compared to cisplatin/5-FU 5
- mDCF had frequent toxicity grades for leukopenia and thrombocytopenia, mostly Grades I and II 6