Premium
Phase I study of paclitaxel with standard dose ifosfamide in children with refractory solid tumors: A Pediatric Oncology Group study (POG 9376)
Author(s) -
Geller James I.,
Wall Donna,
Perentesis John,
Blaney Susan M.,
Bernstein Mark
Publication year - 2009
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.21820
Subject(s) - medicine , ifosfamide , paclitaxel , response evaluation criteria in solid tumors , refractory (planetary science) , sarcoma , chemotherapy , urology , progressive disease , gastroenterology , pathology , cisplatin , physics , astrobiology
Purpose 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). Patients and Methods Paclitaxel was administered as a 6‐hr continuous infusion (hr 0–6), followed by intravenous ifosfamide (2 g/m 2 /day × 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 × 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). Conclusion 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. Pediatr Blood Cancer 2009;52:346–350. © 2008 Wiley‐Liss, Inc.