The objective of this trial is to determine the maximum tolerated dose and the toxicities of
paclitaxel given as a short hour infusion in children with refractory malignancy.
Paclitaxel is an active antitumor agent that has demonstrated a broad range of activity in
preclinical and clinical studies. The optimal dose and schedule has not yet been determined
in either adults or children. The objective of this trial is to determine the maximum
tolerated dose and the toxicities of paclitaxel given as a short hour infusion in children
with refractory malignancy. In addition, the pharmacokinetics of paclitaxel given in this
way will be studied and both model-dependent and model-independent parameters will be
Histologically confirmed cancer (including leukemia) that is: Refractory to standard
therapy (objective disease progression required) OR For which no standard therapy exists
and patient is ineligible for potentially curative surgery.
Recovery from the toxic effects of prior therapy required.
Biologic Therapy: Not specified.
Chemotherapy: No prior taxanes. At least 3 weeks since myelosuppressive therapy (6 weeks
Endocrine Therapy: Not specified.
Radiotherapy: Prior extensive craniospinal or pelvic irradiation allowed.
Surgery: Ineligible for potential curative surgery.
Other: Prior bone marrow transplant allowed.
Age: Over 1 to 21;
Performance status: ECOG 0-2;
Life expectancy: At least 8 weeks.
Hematopoietic: (except with leukemia, bone marrow involvement, history of bone marrow
transplantation, or extensive prior radiotherapy).
Absolute granulocyte count at least 1,500/mm(3);
Platelet count at least 100,000/mm(3);
Hemoglobin at least 8.0 g/dL.
Bilirubin no greater than 1.5 mg/dL;
AST less than 2 times normal.
Creatinine no greater than 1.5 mg/dL OR;
Creatinine clearance at least 60 mL/min per square meter.
No concurrent anticonvulsant therapy.
No grade 2 or worse neuropathy.
No significant systemic illness (e.g., infection) that could compromise drug excretion or
confuse assessment of toxicity.
Not pregnant or nursing.