Irinotecan in Treating Asian Patients With Solid Tumors

OBJECTIVES:

Primary

• To determine the dose-limiting toxicity and maximum tolerated dose of irinotecan hydrochloride according to the genotype status of Asian patients with solid tumors.

Secondary

• To investigate the pharmacokinetics of irinotecan hydrochloride and its metabolites SN-38 and SN-38G.
• To evaluate time to tumor response, response duration, and time to progression in these patients.

OUTLINE: Patients are stratified according to genotype status (UGT1A1*28 vs UGT1A1*6)

Patients receive irinotecan hydrochloride IV once weekly for 3 weeks. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection periodically for pharmacogenetic, pharmacokinetic, and pharmacodynamic studies.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed solid tumors

• Failed at least one line of prior chemotherapy
• Must belong to either Chinese, Malay, or Indian ethnic groups
• Previously irradiated disease allowed provided marker lesions not within the irradiated field
• Presence of at least one bidimensionally measurable, non-CNS indicator lesion, defined by radiologic study (including CT or MRI scan, ultrasound, or chest X-ray) or physical exam, meeting 1 of the following criteria:

• Measurable disease on CT or MRI scan must have one diameter ≥ 1 cm and one diameter ≥ 2 cm
• Measurable disease on chest X-ray or ultrasound must have both diameters ≥ 2 cm
• Palpable tumor masses that cannot be evaluated radiologically must have two diameters ≥ 2 cm
• Measurable skin lesion must have at least one diameter ≥ 1 cm
• No unidimensionally measurable or evaluable only disease
• No known brain or leptomeningeal metastasis
• No uncontrolled large pleural effusions

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 3 months
• Absolute granulocyte count ≥ 1,000/µL
• WBC ≥ 3,500/µL
• Hemoglobin ≥ 9 g/dL
• Platelet count ≥ 100,000/µL
• Serum total bilirubin ≤ 2.0 mg/dL
• ALT/AST < 2.5 times normal (5 times normal in patients with known metastatic disease in the liver)
• Creatinine clearance ≥ 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No medical problems severe enough to prevent compliance with the study requirements
• No prior malignancies, except for adequately treated basal cell or squamous cell carcinoma, carcinoma in situ of the cervix, or other cancer for which the patient has been disease-free for 5 years
• No active or uncontrolled infection
• No pre-existing cardiac disease, including congestive heart failure, arrhythmia requiring treatment, or myocardial infarction within the past 3 months
• No pneumonitis
• No uncontrolled diabetes mellitus (i.e., random blood glucose > 200 mg/dL)
• No inflammatory bowel disease

PRIOR CONCURRENT THERAPY:

• At least 1 week since prior and no concurrent ketoconazole
• More than 4 weeks since prior chemotherapy or radiotherapy
• At least 2 weeks since prior and no concurrent Hypericum perforatum (St. John wort)
• No prior irinotecan hydrochloride
• No concurrent investigational antineoplastic therapy or other investigational drugs