Docetaxel, Capecitabine, and Cisplatin in Treating Patients With Advanced Solid Tumors

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of docetaxel, cisplatin, and capecitabine in patients with advanced solid tumors.
• Determine the dose-limiting toxicity and recommended phase II dose of this regimen in these patients.

Secondary

• Determine the non-dose-limiting toxic effects associated with this regimen in these patients.
• Determine the pharmacokinetics of this regimen in these patients.
• Determine any clinical activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive docetaxel IV over 30 minutes and cisplatin IV over 30 minutes on days 1 and 8 and oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of docetaxel, cisplatin, and capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients receive treatment at the MTD.

PROJECTED ACCRUAL: A minimum of 21 patients will be accrued for this study within 1.5 years.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed solid tumor for which standard curative or palliative measures do not exist or are no longer effective

• Metastatic or unresectable disease
• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 12 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 8.0 g/dL

Hepatic

• AST and ALT ≤ 2.0 times upper limit of normal (ULN) AND alkaline phosphatase [AP] < ULN OR
• AP ≤ 4 times ULN AND AST and ALT < ULN
• Bilirubin normal

Renal

• Creatinine ≤ 1.5 mg/dL OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to ingest oral medications
• No allergy attributed to study drugs, compounds of similar chemical or biological composition, drugs formulated in polysorbate 80, or other agents used in this study
• No inner ear auditory toxicity ≥ grade 2
• No peripheral neuropathy ≥ grade 2
• No immunodeficiency
• No active or ongoing infection
• No psychiatric illness or social situation that would preclude study compliance
• No other concurrent uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent growth factors (sargramostim [GM-CSF] or filgrastim [G-CSF])

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy

• Not specified

Radiotherapy

• More than 4 weeks since prior radiotherapy and recovered

Surgery

• Not specified

Other

• No other concurrent investigational agents unless approved by the principal investigator and medical monitor
• No other concurrent anticancer therapy