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Tepper J et al. J Clin Oncol. 2008;26:1086–1092


Note: The regimen consists of preoperative chemoradiotherapy (cisplatin and fluorouracil) followed by surgery performed between 3 and 8 weeks after completion of radiation therapy in patients who remained operable candidates based on restaging


Hydration before cisplatin: 1000 mL 0.9% sodium chloride (0.9% NS); intravenously over a minimum of 1 hour before commencing cisplatin administration


Cisplatin 100 mg/m2 per dose; administer intravenously in 100–500 mL of 0.9% NS over 30–90 minutes for a total of 2 doses, prior to commencement of fluorouracil infusion, on days 1 and 29 (total dosage during chemoradiation therapy = 200 mg/m2)


Hydration after cisplatin: Administer by intravenous infusion ≥1000 mL 0.9% NS over a minimum of 2 hours. Encourage patients to increase oral intake of non-alcoholic fluids, and provide electrolyte replacement as needed (potassium, magnesium, sodium)


Fluorouracil 1000 mg/m2 per day; administer by continuous intravenous infusion in 500–1000 mL 0.9% NS or 5% dextrose injection (D5W) over 24 hours for 4 consecutive days on days 1–4 and repeated for an additional 4 consecutive days on days 29–32 (total dosage during chemoradiation therapy = 8000 mg/m2)


Radiation 1.8 Gy/day for 5 days/week

Starts concurrently (within 24 hours) of chemotherapy

Planned cumulative dose = 50.4 Gy (duration of planned treatment is 5 weeks, 3 days)

The final 5.4 Gy treatment is given as a boost


Supportive Care

Antiemetic prophylaxis

Emetogenic potential on days with cisplatin is HIGH. Potential for delayed symptoms

Emetogenic potential on days with fluorouracil alone is LOW

Emetogenic potential of radiation therapy to the upper abdomen is MODERATE

See Chapter 39 for antiemetic recommendations


Hematopoietic growth factor (CSF) prophylaxis

Primary prophylaxis is NOT indicated

See Chapter 43 for more information


Antimicrobial prophylaxis

Risk of fever and neutropenia is LOW

  Antimicrobial primary prophylaxis to be considered:

  • Antibacterial—not indicated

  • Antifungal—not indicated

  • Antiviral—not indicated unless patient previously had an episode of HSV

See Chapter 47 for more information

Patient Population Studied

This phase 3 trial (CALGB 9781) involved 56 patients with histologically documented, untreated squamous cell carcinoma or adenocarcinoma of the thoracic esophagus (below 20 cm) or gastroesophageal junction and with <2 cm distal spread into the gastric cardia. The investigators had planned to include 475 patients, but the study was closed early due to poor accrual. Eligible patients had tumors that were considered surgically resectable (T1–3, NX), including regional thoracic lymph node (N1) metastases. Patients with evidence of distant metastatic disease, who had previously received chemotherapy or radiation therapy for this tumor, or who had previously had any radiation therapy that would overlap with radiation fields required for this malignancy, were ineligible. Patients were randomly assigned to receive preoperative chemoradiotherapy followed by surgery or surgery alone. Preoperative chemotherapy included a bolus intravenous infusion of cisplatin (100 mg/m2) over 30 minutes on day 1 followed by a continuous intravenous infusion of fluorouracil (1000 mg/m2 per day) over 96 hours through to day 4, and the same bolus intravenous infusion of cisplatin (100 mg/m2) over 30 minutes on day 29 followed by a continuous intravenous infusion of fluorouracil (1000 mg/m2 per day) over 96 hours through to day 32. Radiotherapy (1.8 Gy/5 days/week for 5.5 weeks; total 50.4 Gy) was scheduled to begin within 24 hours of the start of chemotherapy. Surgery was due to be performed 3–8 weeks after completion of chemoradiotherapy or within 6 weeks of randomization in patients assigned to undergo only surgery.

Efficacy (N = 56)

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Efficacy (N = 56)
  Trimodality Therapy (N = 30) Surgery Alone (N = 26)
Median overall survival 4.48 years 1.79 years
Median progression-free survival 3.47 years 1.01 years
Notes: Median duration of follow-up was 6 years

Therapy Monitoring

  1. Before therapy: History and physical examination. CBC with differential; renal, and liver function tests; serum electrolytes

  2. Monitor renal function prior to initiation and during therapy

  3. CBC with differential every 2 weeks

  4. Within 4 weeks after completion of radiation therapy, restage with a CT scan of the chest and abdomen and repeat esophagogastroduodenoscopy. Patients with progressive or unresectable disease are not offered surgery

Treatment Modifications

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Treatment Modifications


The goal of therapy is to administer the second cycle on time and to avoid treatment delays if possible

Adverse Event Treatment Modification
>G3 hematologic toxicities (ANC <1000/mm3; platelet count <50,000/mm3) Delay dose until ANC is >1500/mm3 and platelet count >100,000/mm3
Febrile neutropenia (ANC <1000/mm3 with single temperature >38.3ºC [101ºF] or a sustained temperature of ≥38ºC [100.4ºF] for more than 1 hour) Hold treatment until neutropenia resolves
Serum creatinine ≥1.5 mg/dL (≥130 µmol/L) and/or BUN ≥25 mg/dL (≥8.92 mmol/L) Withhold cisplatin until serum creatinine <1.5 mg/dL (<130 µmol/L) and BUN <25 mg/dL (<8.92 mmol/L)
Peripheral neuropathy ≥G3 Discontinue cisplatin. G4 discontinue permanently; G3 may reinstitute if toxicity resolves within 2–3 weeks to ≤G1
Cisplatin-induced hearing loss ≥G3
G1 diarrhea (2–3 stools/day > baseline) Maintain dose and schedule
G2 diarrhea (4–6 stools/day > baseline) Delay until diarrhea resolves to baseline, then reduce dosage of fluorouracil by 15–20%
G3 diarrhea (7–9 stools/day > baseline)
G4 diarrhea (≥10 stools/day > baseline) Delay until diarrhea resolves to baseline, then reduce dosage of fluorouracil by 30–40%
Other ≥G3 nonhematologic toxicities (except nausea, vomiting, elevated transaminases, and alopecia) Delay treatment until toxicity resolves to baseline

Adverse Events (N = 28 patients who underwent trimodality therapy)

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Adverse Events (N = 28 patients who underwent trimodality therapy)
Grade (%) Grade 3 Grade 4 Grade 5
Lymphocytes 8 38 0
Esophagitis/dysphagia 27 15 0
White blood cells 25 11 0
Infection 30 0 4
Granulocytes/bands 15 12 0
Pain 16 8 0
Other gastrointestinal 14 5 0
Hemoglobin 11 4 0
Platelets 7 4 0
Nausea 11 0 0
Weight loss 11 0 0
Dysrhythmias 8 0 0

According to the CALGB Expanded Common Toxicity Criteria

Notes: Toxicities are included in the table if grade ≥3 toxicities occurred in ≥10% of the patients receiving trimodality therapy. In total, 57% of patients who received the preoperative chemoradiotherapy experienced at least one grade ≥3 hematologic toxicity. One patient died as a result of treatment-related toxicity (infection)

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