Neoadjuvant Docetaxel and Cisplatin Plus Chemoradiotherapy Followed By Surgery in Treating Patients With Locally Advanced, Resectable Esophageal Cancer

Docetaxel and Cisplatin Chemo- and Radiochemotherapy Followed by Surgery in Patients With Locally Advanced Esophageal Cancer - A Multicenter Phase II Trial

RATIONALE: Drugs used in chemotherapy, such as docetaxel and cisplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving combination chemotherapy with radiation therapy before surgery may shrink the tumor so that it can be removed.

PURPOSE: This phase II trial is studying how well giving docetaxel and cisplatin together with chemoradiotherapy followed by surgery works in treating patients with locally advanced, resectable esophageal cancer.

OBJECTIVES:

Primary

• Determine the effectiveness of neoadjuvant docetaxel and cisplatin and chemoradiotherapy followed by surgery, in terms of pathological response rate, in patients with locally advanced, resectable esophageal cancer.
• Determine the feasibility of this regimen, in terms of successful completion of therapy and survival at 30 days postoperatively, in these patients.

Secondary

• Determine the parameters of disease control in these patients and toxicity of this regimen and compare these parameters with published results.
• Correlate early improvement of dysphasia after 1-2 courses of chemotherapy with predictive value with regard to tumor response and long-term disease control in patients treated with this regimen.
• Determine the quality of life of patients treated with this regimen.
• Determine the clinical benefit of this regimen in these patients.

OUTLINE: This is a multicenter study.

• Neoadjuvant chemotherapy: Patients receive docetaxel IV over 1 hour and cisplatin IV over 1 hour on days 1 and 22.
• Chemoradiotherapy: Beginning 21 days after the last dose of neoadjuvant chemotherapy, patients receive docetaxel IV over 30 minutes and cisplatin IV over 1 hour once a week and undergo radiotherapy 5 days a week for 5 weeks.
• Surgery: Patients undergo surgery 3-8 weeks after the final administration of radiotherapy.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, day 22 of chemotherapy, day 1 of chemoradiotherapy, before surgery, and then every 3 months for 1 year.

Patients are followed every 3 months for 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 22-66 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma or adenocarcinoma of the thoracic esophagus, including the gastroesophageal junction (Siewert type I)

  • Locally advanced disease that is technically operable with curative intent (R0)

  • T3, N0 OR T1-3, N+ OR T4, NX

  • No T1-2, N0

  • No inoperable T4 (unequivocal organ involvement)

  • No distant metastasis, including M1a lymph node status

    • Lymph nodes suspicious of M1a status by CT scan, PET scan, or ultrasound must be verified by fine-needle aspiration cytology

• No carcinoma of the cervical esophagus

• Obstructive tumors allowed

PATIENT CHARACTERISTICS:

Age

• 18 to 70

Performance status

• WHO 0-1

Life expectancy

• Not specified

Hematopoietic

• Neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• AST no greater than 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2.5 times ULN
• Bilirubin no greater than 1.5 times ULN

Renal

• Creatinine clearance greater than 60 mL/min

Cardiovascular

• No New York Heart Association class III or IV congestive heart failure
• No unstable angina pectoris
• No myocardial infarction within the past 3 months
• No significant arrhythmias
• No other severe or uncontrolled cardiovascular disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 12 months after study treatment
• No definite contraindications to corticosteroids as premedication
• No geographic situation that would preclude proper staging and follow-up
• No active uncontrolled infection
• No preexisting peripheral neuropathy greater than grade 1
• No uncontrolled diabetes mellitus
• No active autoimmune disease
• No other serious medical condition that would preclude study participation
• No other prior or concurrent malignancy except nonmelanoma skin cancer or adequately treated carcinoma in situ of the cervix
• No significant neurologic or psychiatric disorder, including psychotic disorders, dementia, or seizures that would preclude comprehension and ability to provide informed consent and complete quality of life questionnaires

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy to the chest

Surgery

• Not specified

Other

• More than 30 days since prior treatment on another clinical trial
• No other concurrent experimental drugs