Radiation Therapy, Pemetrexed Disodium, and Carboplatin in Treating Patients With Locally Advanced Esophageal Cancer That Can Be Removed By Surgery

OBJECTIVES:

Primary

* Determine the pathologic complete response rate of radiotherapy, pemetrexed disodium, and
carboplatin when administered prior to esophagectomy in patients with locally advanced
esophageal cancer.

Secondary

- Determine the activity, in terms of clinical response rate and adverse event profile of
radiotherapy, pemetrexed disodium, and carboplatin when administered prior to
esophagectomy.

- Determine the overall survival, time-to-progression, and time-to-treatment failure for
patients receiving the above combined modality treatment.

- Determine the surgical outcome for all patients who undergo esophagectomy.

- Determine the time-to-disease recurrence and disease-free survival for patients who
have a curative resection.

- Determine quality of life of patients treated with this regimen. OUTLINE: This is a
multicenter study. Patients undergo radiotherapy once daily, 5 days a week, for 5 ½
weeks and concurrently receive pemetrexed disodium IV over 10 minutes and carboplatin
IV over 30 minutes on days 1 and 22. Treatment continues in the absence of disease
progression or unacceptable toxicity. Patients who are eligible will undergo
esophagectomy between 4-12 weeks after completion of radiotherapy.

Quality of life is assessed at baseline, immediately prior to day 22 of chemotherapy, and
within 2 weeks prior to surgery.

After completion of study treatment, patients are followed periodically for approximately 4
years.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed squamous cell carcinoma or adenocarcinoma
of the esophagus or gastroesophageal (GE) junction

- No T1-2, N0, M0 disease

- No palpable or biopsy-proven involvement of supraclavicular nodes or
radiographically involved supraclavicular nodes (> 1.5 cm in greatest dimension)
for lesions in mid-thoracic, distal thoracic, or GE junction

+ Supraclavicular node involvement allowed provided there are upper thoracic
esophagus primary lesions

- Patients with involvement of celiac nodes (stations 15-20) are eligible if the
primary lesion is mid-thoracic, distal esophagus, or GE junction

- No evidence of distant metastases

- Tumor must be considered surgically resectable

- Patients with T4, N0 tumors that are potentially resectable are eligible

- No clinically relevant pleural or peritoneal effusion that is not amenable to
drainage

PATIENT CHARACTERISTICS:

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Life expectancy ≥ 12 weeks

- Absolute neutrophil count ≥1,500/mm^3

- Platelet count ≥100,000/mm^3

- Hemoglobin ≥10 g/dL

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST ≤ 3 times ULN

- Creatinine clearance ≥ 45 mL/min

- No New York Heart Association class III or IV congestive heart failure

- Pregnant or nursing women are ineligible

- Negative pregnancy test

- Fertile patients must use effective contraception

- No uncontrolled infection

- No other severe underlying disease that would preclude study entry

- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer or carcinoma in situ

- No prior sensitivity or allergic reaction to pemetrexed disodium or carboplatin

- Able to swallow pills

PRIOR CONCURRENT THERAPY:

- No prior chemotherapy for esophageal cancer

- No prior radiotherapy field that overlapped the anticipated fields of study
radiotherapy

- No prior radiotherapy to > 30% of the marrow cavity

- Patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) must be able to
discontinue use 2 days prior, during, and 2 days after pemetrexed disodium
administration (5 days prior for long-life NSAIDs)

- Patients must not have been receiving cyclooxygenase-2 inhibitors at study entry and
while receiving protocol therapy