Phase I study of paclitaxel with standard dose ifosfamide in children with refractory solid tumors: a Pediatric Oncology Group study (POG 9376).
OBJECTIVE
A dose-escalation Phase I study of taxol (paclitaxel) administered in combination with standard dose ifosfamide was conducted in children with relapsed or refractory solid tumors. Primary objectives were to estimate the maximum tolerated dose (MTD) and to describe the dose-limiting toxicities (DLTs).


METHODS
Paclitaxel was administered as a 6-hr continuous infusion (hr 0-6), followed by intravenous ifosfamide (2 g/m(2)/day x 3 days) over 1 hr at hours 6-7, 24-25, and 48-49. Patients at dose level 1 received 250 mg/m(2) paclitaxel. Subsequent dose escalation proceeded using a standard 3 x 3 Phase I design.


RESULTS
Fifteen patients received a combined 46 courses of therapy. The median age was 14.5 years (range, 2-19 years), and diagnoses included sarcoma (7), neuroblastoma (3), and other (5). Three patients received paclitaxel at 250 mg/m(2) (10 courses), six at 325 mg/m(2) (19 courses), three at 425 mg/m(2) (8 courses), and three at 550 mg/m(2) (9 courses). DLTs occurred in 2/3 patients at 550 mg/m(2) paclitaxel during cycle 1, including grade 3 hypotension and grade 4 anaphylaxis in 1 patient each. Common non-dose-limiting toxicities included bone marrow suppression and peripheral neuropathy. Response was evaluable in 14 patients and included mixed response (3), stable disease (5), and progressive disease (6).


CONCLUSIONS
Paclitaxel hypersensitivity reactions were dose limiting when the drug was administered as a 6-hr infusion. The MTD and recommended Phase II dose of paclitaxel administered as a 6-hr continuous intravenous infusion followed by standard dose intravenous ifosfamide is 425 mg/m(2) paclitaxel.
Geller
James I
JI
Department of Hematology-Oncology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229-3039, USA.
Wall
Donna
D
Perentesis
John
J
Blaney
Susan M
SM
Bernstein
Mark
M
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
D017239:Paclitaxel; D007069:Ifosfamide