Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Esophageal Cancer

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Completed; Phase 1

Conditions: Gastric Cancer; Esophageal Cancer

Treatments: Drug: irinotecan hydrochloride; Drug: cisplatin; Radiation: radiation therapy

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00005638

CDR0000067794 (Registry Identifier)

NCI-G00-1766

99-081

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy 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. Combining chemotherapy with radiation therapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of chemotherapy plus radiation therapy in treating patients who have advanced cancer of the esophagus.

Full description

OBJECTIVES:

• Determine the dose limiting toxicity of irinotecan when given weekly with cisplatin and concurrent external beam multifield radiotherapy in patients with locally advanced carcinoma of the esophagus or gastroesophageal junction.
• Determine the maximum tolerated dose and the recommended phase II dose of irinotecan in this regimen in this patient population.
• Evaluate the complete response rate in these patients to one course of induction chemotherapy followed by concurrent chemotherapy and radiotherapy.

OUTLINE: This is a dose escalation study of irinotecan.

Patients receive induction chemotherapy with cisplatin IV over 30 minutes followed by irinotecan IV over 30 minutes on days 1, 8, 15, and 22. Following 2 weeks of rest, patients begin chemoradiation. Patients receive cisplatin and irinotecan as above on days 1, 8, 22, and 29 and radiotherapy once daily 5 days a week for 5-6 weeks.

Cohorts of 3-6 patients receive escalating doses of irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities.

Patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for this study.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction

  • T1, N1, M0 or T2-4, Nx, M0

    • No supraclavicular or celiac lymph nodes

• Previously untreated, newly diagnosed tumors OR

• Prior resection without adjuvant therapy with local regional failure

  • Positive microscopic margin on resection of all gross disease allowed provided no metastatic disease

• No positive malignant cytology of the pleura, pericardium, or peritoneum

• No biopsy proven tumor invasion of the tracheobronchial tree or tracheoesophageal fistula

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 70-100% OR
• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9.0 g/dL

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• No known Gilbert's disease

Renal:

• Creatinine no greater than 1.5 mg/dL
• No hypercalcemia

Cardiovascular:

• No New York Heart Association class III or IV heart disease
• No myocardial infarction within the past 6 months
• No uncontrolled hypertension

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other severe concurrent conditions (e.g., severe uncontrolled diabetes, uncontrolled infections, or cerebral vascular disease)
• No other malignancy within the past 5 years except basal cell carcinoma of the skin or carcinoma in situ of the cervix
• No history of seizure disorder currently receiving phenytoin, phenobarbital, or other antiepileptic medication
• No other concurrent medical or psychiatric condition or disease that would preclude study entry

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy for esophageal cancer including adjuvant chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy for esophageal cancer including adjuvant radiotherapy
• No prior mantle, chest, pelvic, or hemibody radiotherapy

Surgery:

• See Disease Characteristics

Other:

• No concurrent prochlorperazine on day of irinotecan administration