Irinotecan and Paclitaxel in Treating Patients With Metastatic or Recurrent Cancer of the Esophagus or Stomach

OBJECTIVES:

- Determine the antitumor activity of irinotecan and paclitaxel in patients with
metastatic or recurrent adenocarcinoma of the esophagus or stomach.

- Determine the toxic effects of this regimen in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to diagnosis
(adenocarcinoma of the esophagus, gastroesophageal junction, or gastric cardia vs
adenocarcinoma of the rest of the stomach).

Patients receive irinotecan IV over 90 minutes followed by paclitaxel IV over 3 hours on day
1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable
toxicity.

Patients are followed at 30 days and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 26-54 patients (13-27 per stratum) will be accrued for this
study.

Inclusion Criteria

- Patients with histologic proof of adenocarcinoma of the esophagus (including GE
junction) or adenocarcinoma of the stomach will be eligible.

- Location of the tumor for assignment to study will be determined by prior endoscopy
or barium contrast study.

- Patients must have either metastatic or recurrent cancer.

- Patients must have bidimensionally measurable disease, as defined in Section 8.4.1.1,
page 16. Mediastinal or hilar lymph nodes assessed by CT or MRI scans must be at
least 2 cm in the largest dimension to be considered measurable.

- Prior limited radiation therapy is permitted. Prior radiotherapy must not have
included major bone marrow containing areas (pelvis, lumbar spine), or contained the
single evaluable lesion in a radiation field. A recovery period of at least 4 weeks
after completion of radiotherapy is required prior to study treatment.

- Patients must have an anticipated life expectancy of at least 12 weeks.

- Patients must have a performance status of 0 or 1 on the ECOG performance scale.

- Patients must be > 18 years old.

- Patients must give written informed consent prior to enrollment.

- Patients should have adequate organ function defined as follows: Absolute
granulocytes > 1,500/mm3 and platelets > 100,000/mm3; serum bilirubin < 1.5 mg/dL and
SGOT < 3X upper limit of institutional norm; and serum creatinine < 1.5 mg/dL.

- Patients must have recovered from recent surgery. One week must have elapsed from the
time of a minor surgery and 3 weeks from major surgery.

Exclusion Criteria

- Patients who have received more than one prior chemotherapy regimen or immunotherapy
for metastatic disease. Prior 5-FU alone as an adjuvant therapy or radiosensitizer is
not counted. Patients must have an interval of 4 weeks from prior chemotherapy or
immunotherapy with full recovery.

- Patients receiving concurrent chemotherapy, immunotherapy, or radiotherapy.

- Patients who are potentially curable with a chemotherapy, radiotherapy, surgery, or
any combination of the above.

- Patients with known brain metastases.

- Patients with a history of seizures or are receiving phenytoin, phenobarbital, or
other antiepileptic prophylaxis.

- Pregnant or lactating women. All women of childbearing potential must have a negative
pregnancy test prior to entry into the study. All patients of procreative potential
must be advised of the importance of avoiding pregnancy and using appropriate methods
of contraception while participating in this investigational trial.

- Patients with serious intercurrent infections, or any other concurrent disease which,
in the investigator's judgment, would make the patient inappropriate for entry into
this study.

- Patients with psychiatric disorders rendering them incapable of complying with the
requirements of the protocol.

- Patients with osseous metastasis as only site of disease.

- Patients with any concurrent active malignancy other than non-melanoma skin cancers
or carcinoma-in-situ of the cervix. Patients with previous malignancies but without
evidence of disease for > 5 years will be allowed to enter the trial.

- Patients with known Gilbert's syndrome.

- Patients who have a significant clinical neuropathy of greater than grade 2.

- Patients with unstable angina, a history of myocardial infarction within the previous
6 months, or current clinical evidence of congestive heart failure. Patients taking
medication for congestive heart failure and showing no clinical signs or symptoms are
eligible.

- Patients who have previously received a taxane or campthothecin

- Patients who have received any investigational therapy within the previous 4 weeks.