DX-8951f in Treating Patients With Metastatic Stomach Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of exatecan mesylate in treating patients who have metastatic stomach cancer.

OBJECTIVES:

* Determine the objective response rate of patients with previously untreated metastatic gastric cancer treated with exatecan mesylate (DX-8951f).
* Determine the time to tumor progression in this patient population when treated with this drug.
* Determine the survival at 6 and 12 months in this patient population when treated with this drug.
* Determine the quantitative and qualitative toxic effects of this drug in this patient population.
* Determine the pharmacokinetics of this drug in the plasma of these patients.

OUTLINE: This is a multicenter study.

Patients receive exatecan mesylate (DX-8951f) IV over 30 minutes on days 1-5. Treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 12-37 patients will be accrued for this study within 12 months.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically confirmed gastric or gastroesophageal adenocarcinoma

  * Lymph node involvement and/or distant metastasis
* No squamous cell carcinoma, small cell carcinoma, lymphoma, or leiomyosarcoma of the stomach
* Measurable disease with indicator lesions outside the field of prior radiotherapy

  * At least 20 mm by conventional scan OR
  * At least 10 mm by spiral CT scan
  * Nonmeasurable lesions include the following:

    * Primary tumor
    * Bone lesions
    * Leptomeningeal disease
    * Ascites
    * Pleural/pericardial effusion
    * Inflammatory breast disease
    * Lymphangitis cutis/pulmonitis
    * Cystic lesions
    * Abdominal masses not confirmed and followed by imaging techniques
* No prior treatment for locally advanced or metastatic disease

  * Prior adjuvant treatment allowed if disease recurrence noted at least 6 months after completion of adjuvant treatment
* No known brain metastases

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* ECOG 0-2

Life expectancy:

* At least 12 weeks

Hematopoietic:

* Absolute neutrophil count at least 1,500/mm3
* Platelet count at least 100,000/mm3
* Hemoglobin at least 9.0 g/dL

Hepatic:

* Bilirubin no greater than 2.0 mg/dL
* AST or ALT no greater than 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases present)
* Albumin at least 2.8 g/dL
* PT or INR no greater than 1.5 times ULN (coumadin independent)

Renal:

* Creatinine no greater than 1.5 mg/dL

Cardiovascular:

* No active congestive heart failure
* No uncontrolled angina
* No myocardial infarction within the past 6 months

Other:

* No concurrent serious infection
* No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
* No overt psychosis, mental disability, or incompetence that would preclude informed consent
* No other life-threatening illness
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics

Biologic therapy:

* No concurrent anti-cancer biologic therapy
* No concurrent prophylactic colony stimulating factors during first course of therapy

Chemotherapy:

* Recovered from prior adjuvant chemotherapy
* No other concurrent anti-cancer chemotherapy
* No other concurrent anti-cancer cytotoxic therapy

Endocrine therapy:

* Concurrent megestrol for appetite stimulation allowed

Radiotherapy:

* At least 4 weeks since prior radiotherapy and recovered
* No prior wide-field radiotherapy to more than 25% of bone marrow
* No concurrent anti-cancer radiotherapy

Surgery:

* At least 4 weeks since prior major surgery and recovered
* No concurrent anti-cancer surgery

Other:

* No other investigational drugs (including analgesics or antiemetics) for at least 4 weeks prior to, during, and for 4 weeks after study