Docetaxel in Treating Patients With Solid Tumors

OBJECTIVES:

• Compare the population pharmacokinetics of docetaxel in Caucasians and African American patients with solid tumors.
• Compare the pharmacodynamic effect of a single dose of docetaxel in relation to hematological toxicity in these patient populations.
• Determine the CYP3A4 genotype and P-glycoprotein (P-gp) expression and their relationship to docetaxel clearance in these patient populations.

OUTLINE: Patients receive docetaxel IV over 1 hour on day 1. Patients may receive additional courses beginning 21 days after the first docetaxel dose at the discretion of the physician.

DISEASE CHARACTERISTICS:

• Histologically proven unresectable solid tumors (e.g., lung, breast, head and neck, bladder)
• Clinically suitable for treatment with single agent docetaxel
• Caucasian (at least 2 generations originating in any of the original peoples of Europe, North Africa, or the Middle East) OR
• African American (at least 2 generations originating in any of the black racial groups of Africa)

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• 0-2

Hematopoietic:

• Granulocyte count at least 1,500/mm3
• Platelet count at least 100,000/mm3

Hepatic:

• Bilirubin no greater than upper limit of normal (ULN)
• AST no greater than 1.5 times ULN AND
• Alkaline phosphatase no greater than 2.5 times ULN

Renal:

• BUN no greater than 1.5 times ULN
• Creatinine no greater 1.5 times ULN

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior bone marrow transplantation

Chemotherapy:

• No prior docetaxel
• Prior paclitaxel allowed
• 1 or 2 prior chemotherapy regimens allowed
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent hormones for disease related conditions
• Concurrent steroids for adrenal failure allowed

Radiotherapy:

• At least 2 weeks since prior radiotherapy
• Palliative radiotherapy allowed except whole brain irradiation for CNS disease

Surgery:

• Not specified

Other:

• At least 48 hours since prior or concurrent ethanol (CYP3A enzyme inducer) or grapefruit juice (CYP3A enzyme inhibitor)
• At least 7 days since prior or concurrent CYP450 inducing drugs:

• Antiseizure medications: phenobarbital, phenytoin, carbamazepine, or lamotrigine
• Anti-TB therapy: rifampin, isoniazid, or sulfinpyrazone
• At least 7 days since prior or concurrent CYP450 3A inhibiting drugs:

• Macrolides: erythromycin, clarithromycin, azithromycin, or roxithromycin
• Azoles: ketoconazole, fluconazole, or itraconazole
• Other antibiotics: metronidazole or chloramphenicol
• Anti-HIV drugs: ritonavir, indinavir, nelfinavir, or delavirdine
• Immunosuppressive agents: cyclosporine
• Antidepressant agent: nefazodone