Cisplatin, Irinotecan, and Radiation Therapy in Treating Patients With Esophageal Cancer or Gastroesophageal Junction Cancer That Can Be Removed By Surgery

PRIMARY OBJECTIVES:

I. To determine the pathologic complete response rate in patients with surgically resectable
esophageal cancer treated pre-operatively with induction chemotherapy with weekly cisplatin
and irinotecan (irinotecan hydrochloride) followed by concurrent cisplatin/irinotecan and
radiation therapy.

SECONDARY OBJECTIVES:

I. To evaluate potential response or progression of disease during induction chemotherapy
with positron emission tomography (PET) scan.

II. To evaluate the toxicity and tolerability of therapy, including surgical morbidity and
mortality.

III. To determine the overall survival, disease free survival, and pattern of failure.

OUTLINE:

INDUCTION CHEMOTHERAPY (COURSES 1-2): Patients receive cisplatin intravenously (IV) over 30
minutes and irinotecan hydrochloride IV over 30-90 minutes on days 1 and 8 of courses 1 and
2. Treatment repeats every 21 days for 2 courses in the absence of disease progression or
unacceptable toxicity.

CHEMORADIOTHERAPY (COURSES 3-4): Beginning 2 weeks after completion of induction
chemotherapy, patients receive cisplatin and irinotecan hydrochloride as in induction
chemotherapy on days 1 and 8 of courses 3 and 4 and undergo radiotherapy daily 5 days a week
in course 3. Treatment repeats every 21 days for 2 courses in the absence of disease
progression or unacceptable toxicity.

SURGERY: Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo
surgery to remove the tumor.

After completion of study treatment, patients are followed up every 3 months for 2 years and
then every 6 months for 3 years.

- Histologically or cytologically confirmed adenocarcinoma, poorly differentiated
carcinoma, or carcinoma not otherwise specified, of the esophagus or gastroesophageal
junction; biopsy or cytology of the primary tumor, or of involved regional lymph
nodes, is acceptable

- Tumors must be TNM stage T2-4, N0-1, M0 as determined by pretreatment endoscopic
ultrasound; T1 tumors are eligible if they are T1, N1, M0; regional thoracic lymph
node involvement (N1) is permitted

- Disease must be clinically limited to the esophagus or gastroesophageal junction; if
the tumor extends below the gastroesophageal junction into the proximal stomach, 50%
of the tumor must involve the distal esophagus or gastroesophageal junction;
adenocarcinomas of the distal esophagus would therefore include tumors of the distal
esophagus, or Siewert type I according to the Siewert classification, and tumors of
the gastroesophageal junction which involve equally both the distal esophagus and
proximal stomach, or Siewert type II; tumor must be surgically resectable

- No TIS (in-situ carcinoma) and tumors determined to be T1N0 following endoscopic
ultrasound

- No clinical involvement on endoscopic ultrasound (EUS), computed tomography (CT)
scan, or PET scan of supraclavicular or celiac lymph node involvement (stage IVa,
T any N any M1a) unless this is proven to be a false positive by an appropriate
biopsy

- No patients with cervical esophageal tumors, or gastric cancers with minor
involvement of the gastroesophageal junction or distal esophagus

- No patients with tracheoesophageal fistulas

- Patients with evidence of metastatic disease are not eligible; this includes:

- Positive malignant cytology of the pleura, pericardium or peritoneum

- Radiographic evidence of distance organ involvement including lung, liver, bone,
or brain

- No prior chemotherapy or radiotherapy is permitted; patients must be at least 4 weeks
since major surgery, or must have recovered from the effects of minor surgery
(laparoscopy, thoracoscopy)

- No prior malignancies (other than basal cell/squamous carcinoma of the skin, in-situ
cervical carcinoma, or superficial transitional cell bladder carcinoma) are permitted
unless diagnosed and/or treated >= 3 years before registration and without evidence of
recurrence

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1

- No evidence of recurrent laryngeal nerve or phrenic nerve paralysis

- No known Gilbert's disease

- No clinically significant hearing loss; audiograms should be done in patients in which
they are clinically indicated

- No history of active seizure disorder; no ongoing treatment with phenytoin,
phenobarbital, or other antiepileptic medication; patients who are receiving valproic
acid are eligible

- No New York Heart Association class III or IV heart disease; no angina or myocardial
infarction within the last 6 months

Inclusion Criteria:

- No history of clinically significant ventricular arrhythmia requiring ongoing
medication with antiarrhythmics

- Absolute neutrophil count (ANC) >= 1,500/ul

- Platelet count >= 100,000/ul

- Hemoglobin >= 9 gm/dl

- Serum creatinine =< upper limit of normal (ULN)

- Total serum bilirubin =< 1.5 mg/dl

- Forced expiratory volume in 1 second (FEV-1) >= 1.2 liters OR >= 35% of normal as a
value that is indexed to body size

- Pulmonary function tests (PFT) >= 1.2 liters OR >= 35% of normal as a value that is
indexed to body size