PMID- 16234526
OWN - NLM
STAT- MEDLINE
DCOM- 20051121
LR  - 20181201
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 23
IP  - 30
DP  - 2005 Oct 20
TI  - Phase I study of O6-benzylguanine and temozolomide administered daily for 5 days 
      to pediatric patients with solid tumors.
PG  - 7646-53
AB  - PURPOSE: This pediatric phase I trial of O6-benzylguanine (O6BG) and temozolomide 
      (TMZ) on a daily schedule for 5 days, every 28 days was performed to determine 
      the maximum-tolerated dose of TMZ when given with a biologically active dose of 
      O6BG and to define the toxicity profile of the combination in children with solid 
      tumors. PATIENTS AND METHODS: Patients < or = 21 years old with refractory solid 
      tumors were eligible. O6BG was administered intravenously over 60 minutes daily 
      for 5 days. TMZ was administered orally 30 minutes after completion of each O6BG 
      infusion. Starting doses of O6BG and TMZ were 60 mg/m2/d and 28 mg/m2/d, 
      respectively. O6BG was escalated to 90 and 120 mg/m2/d; TMZ was subsequently 
      escalated to 40, 55, 75, and 100 mg/m2/d. Cycles were repeated every 28 days. 
      RESULTS: Forty-one patients were enrolled; 32 patients were assessable for 
      toxicity. The combination of O6BG and TMZ was tolerable at TMZ doses less than 
      half of the conventional dose of 200 mg/m2/d. Myelosuppression occurred 
      sporadically at all dose levels and was the dose-limiting toxicity (DLT) at 100 
      mg/m2/d of TMZ combined with 120 mg/m2/d O6BG. Nonhematologic toxicities were 
      generally mild. Evidence of antitumor activity was observed at 120 mg/m2/d O6BG 
      combined with TMZ doses of 55 mg/m2/d and above. CONCLUSION: The recommended 
      doses of O6BG administered with TMZ on a 5-day schedule in children are 120 
      mg/m2/d of O6BG and 75 mg/m2/d of TMZ. Evidence of activity was observed at these 
      doses. Myelosuppression was the DLT.
FAU - Warren, Katherine E
AU  - Warren KE
AD  - National Cancer Institute Neuro-Oncology Branch, Building 82, Room 219, 9030 Old 
      Georgetown Rd, Bethesda, MD 20892-8200, USA. warrenk@mail.nih.gov
FAU - Aikin, Alberta A
AU  - Aikin AA
FAU - Libucha, Madeleine
AU  - Libucha M
FAU - Widemann, Brigitte C
AU  - Widemann BC
FAU - Fox, Elizabeth
AU  - Fox E
FAU - Packer, Roger J
AU  - Packer RJ
FAU - Balis, Frank M
AU  - Balis FM
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Journal Article
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 01KC87F8FE (O(6)-benzylguanine)
RN  - 5Z93L87A1R (Guanine)
RN  - 7GR28W0FJI (Dacarbazine)
RN  - YF1K15M17Y (Temozolomide)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Child
MH  - Child, Preschool
MH  - Dacarbazine/administration & dosage/analogs & derivatives
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Female
MH  - Guanine/administration & dosage/analogs & derivatives
MH  - Humans
MH  - Injections, Intravenous
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Neoplasms/*drug therapy
MH  - Prognosis
MH  - Temozolomide
EDAT- 2005/10/20 09:00
MHDA- 2005/12/13 09:00
CRDT- 2005/10/20 09:00
PHST- 2005/10/20 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/10/20 09:00 [entrez]
AID - 23/30/7646 [pii]
AID - 10.1200/JCO.2005.02.0024 [doi]
PST - ppublish
SO  - J Clin Oncol. 2005 Oct 20;23(30):7646-53. doi: 10.1200/JCO.2005.02.0024.