A Phase I Pharmacokinetic Study Of Epothilone B Analogue BMS-247550 (NSC 710428D) In Patients With Advanced Malignancies And Varying Levels Of Liver Dysfunction

Inclusion Criteria

DISEASE CHARACTERISTICS:

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

- Pathological confirmation of diagnosis not required in patients with liver mass,
raised alpha-fetoprotein levels (at least 500 ng/mL), and positive serology for
hepatitis consistent with a diagnosis of hepatocellular carcinoma

- Any solid tumor or lymphoma tumor type eligible

- Must have had thoracic and upper abdominal CT scan, including entire liver and
adrenals, within 28 days before study entry

- Patients with glioma or brain metastases must be on a stable dose of corticosteroids
and be seizure-free for the past month

- Prior whole brain or gamma knife radiotherapy required for known brain
metastases

- No unstable or untreated (non-irradiated) brain metastases

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- Zubrod 0-2

Life expectancy

- Not specified

Hematopoietic

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- No active hemolysis

Hepatic

- See Disease Characteristics

- Patients with biliary obstruction for which a shunt has been placed are allowed if
shunt is in place for at least 10 days and liver function is stable

- Abnormal liver function (bilirubin and SGOT) allowed regardless of cause (metastases
or other causes)

- No evidence of biliary sepsis

Renal

- Creatinine no greater than 1.5 mg/dL

Cardiovascular

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

Other

- No concurrent uncontrolled illness

- No ongoing or active infection

- No uncontrolled diarrhea

- No peripheral neuropathy grade II or greater

- No psychiatric illness or social situation that would preclude study compliance

- HIV negative

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No concurrent immunotherapy for malignancy

Chemotherapy

- More than 2 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

- No other concurrent chemotherapy for malignancy

Endocrine therapy

- See Disease Characteristics

- No concurrent oral contraceptives

- No concurrent hormone therapy for malignancy

- Concurrent luteinizing hormone-releasing hormone agonists allowed

Radiotherapy

- See Disease Characteristics

- More than 4 weeks since prior radiotherapy and recovered

- No concurrent radiotherapy for malignancy

Surgery

- More than 2 weeks since prior major surgery

Other

- Recovered from prior therapy

- No concurrent medications that are known to be inhibitors of CYP3A4