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

• Clinical tumor response [ Designated as safety issue: No ]
• Pathologic tumor response [ Designated as safety issue: No ]
• Time to disease progression [ Designated as safety issue: No ]
• Surgical outcome [ Designated as safety issue: No ]
• Time to death [ Designated as safety issue: No ]
• Disease-free survival [ Designated as safety issue: No ]
• Time to treatment failure [ Designated as safety issue: No ]
• Quality of life [ Designated as safety issue: No ]

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as pemetrexed disodium and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pemetrexed disodium may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving radiation therapy together with pemetrexed disodium and carboplatin before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying how well giving radiation therapy together with pemetrexed disodium and carboplatin works 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 to surgery 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.

• Drug: carboplatin
• Drug: pemetrexed disodium
• Procedure: conventional surgery
• Procedure: neoadjuvant therapy
• Radiation: radiation therapy

• Jatoi A, Soori G, Foster NR, Hiatt BK, Knost JA, Fitch TR, Callister MD, Nichols FC 3rd, Husted TM, Alberts SR. Phase II study of preoperative pemetrexed, carboplatin, and radiation followed by surgery for locally advanced esophageal cancer and gastroesophageal junction tumors. J Thorac Oncol. 2010 Dec;5(12):1994-8.
• Katipamula R, Jatoi A, Foster NR, Nichols F, Rubin J, Callister M, Gunderson L, Alberts S. Pemetrexed, Carboplatin, and Concomitant Radiation followed by Surgery for Locally Advanced Esophageal Cancer: Results of a Planned Interim Toxicity Analysis of North Central Cancer Treatment Group Study N044E. Clin Med Oncol. 2008;2:223-5. Epub 2008 Apr 1.

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:

• 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