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

Swiss Group for Clinical Cancer Research

Status and phase: Completed; Phase 2

Conditions: Esophageal Cancer

Treatments: Drug: Cisplatin and Docetaxel

Study type: Interventional

Funder types: Other

Identifiers

NCT00072033

EU-20323

SAKK 75/02

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 66 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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66 participants in 1 patient group

Arm A

Active Comparator group

Description:

Docetaxel and Cisplatin chemo- and radiochemotherapy followed by surgery

Treatment:

Drug: Cisplatin and Docetaxel