Table 1.

Pediatric Oncology Branch solid tumor phase I trials included in analysis

					Dose level
Study no.	Drug	Mechanism of action	Schedule	MTD/recommended dose	At MTD	Total n	n of patientsa	DLT	Study
Myelosuppressive agent
1	Docetaxelb–d	Microtubule-stabilizing agent	1-hour i.v. × 1 day every 21 days	65 mg/m2	3e	9	10	M	Blaney et al. [10], Seibel et al. [11]
2	Ixabepilone	Microtubule-stabilizing agent	1-hour i.v. daily × 5 days every 21 days	8 mg/m2	4	5	13	M, F	Widemann et al. [19]
3	Lipodoxb	Liposomal doxorubicin	1-hour i.v. × 1 day every 21 days	60 mg/m2	2	3	15	M	Lowe et al. [8]
4	Paclitaxel	Microtubule-stabilizing agent	3-hour i.v. × 1 day every 21 days	250 mg/m2	2	3	9	Ne, M	Berg et al. [20]
5	Pyrazoloacridined	DNA-binding agent	1-hour i.v. × 1 day or 24-hour i.v. × 1 day every 21 days	640 mg/m2	3	4	19	M	Berg et al. [9]
6	Tipifarnibb	Farnesyltransferase inhibitor	Orally twice daily × 21 days every 28 days	200 mg/m2	2	4	14	M, R, GI	Widemann et al. [12]
7	Tomudexb	Antifolate, TS inhibition	15-minute i.v. × 1 day every 21 days	6 mg/m2	7	8	9	M, H, GI, R	Widemann et al. [18]
Nonmyelosuppressive agent
8	9-Cis-retinoic acidb,d	Differentiating agent	Orally, three times a day × 28 days	≤ 12 yrs, 35 mg/m2; >12 yrs, 85 mg/m2	1 3	2 4	15	CNS	Adamson et al. [14]
9	ABT-751b	Microtubule-destabilizing agent	Orally daily × 7 days every 21 days Orally daily × 21 days	200 mg/m2 100 mg/m2	4 2	5 4	20 7	Ne, HTN, F Ne, HTN, M, F, GI	Fox et al. [13] Fox et al. [23]
10	ATRAf/INF-α2Ab,d	Differentiating agent/immunomodulator	Orally 3 days/wk/ 3 × 106 U/m2 s.c. 5 days/wk	90 mg/m2	2	3	14	CNS	Adamson et al. [32]
11	Phenylacetateb	Differentiating agent	24-hour i.v. every 28 days	9 gm/m2	4	5	20	S	Serabe et al. [22]
12	Phenylbutyrateb	Differentiating agent	24-hour i.v. every 28 days	12.5 gm/m2	2	3	4	S	Serabe et al. [21]
13	SU101d	PDGF receptor inhibitor	96-hour i.v. every 21 days	390 mg/m2	3	4	16	CNS	Adamson et al. [15]
Modulating agent plus standard chemotherapy
14	Lobradimilf/carboplatin	Bradykinin analogue/platination	10-minute i.v. with carboplatin infusion × 2 days every 28 days	600 ng/kg IBW	4	4	21	Noneg	Warren et al. [17]
15	Tariquidarf + CT	P-glycoprotein inhibitor/CT	30-minute i.v. prior to CT dose every 21 days	2 mg/kg	3	3	19	Noneg	Fox et al. [7]
16	Temozolomidef/O6BG	Alkylator/AGT inactivator	Orally/i.v. × 5 days every 28 days	75 or 120 mg/m2	6h	7h	37	M	Warren et al. [33]

^aNumber of patients enrolled in the trial at the NCI.

^bMulti-institutional trial.

^cStudy included in Carlson et al. [4] review.

^dStudy included in Lee et. al. [6] review.

^eMTD originally determined to be 65 mg/m² (dose level 3). After establishing new eligibility criteria, excluding heavily pretreated patients, the MTD was determined to be 125 mg/m² (dose level 6). After adding filgrastim, dose level 8 (185 mg/m²) was defined as the MTD.

^fInvestigational agent used in stratification for regression analysis.

^gNone observed for modulating agent.

^hFirst three dose levels required to achieve biologically active dose of O⁶BG at constant temozolomide dose. Abbreviations: AGT, 0⁶ alklyguanine-DNA aklytransferase; ATRA, all trans retinoic acid; CNS, central nervous system; CT, chemotherapy (either docetaxel, vinorelbine, or doxorubicin); DLT, dose-limiting toxicity; F, fatigue; GI, nausea, vomiting, diarrhea, abdominal pain, or constipation; H, hepatotoxicity; HTN, hypertension; IBW, ideal body weight; INF, interferon; M, myelosuppression; MTD, maximum-tolerated dose; NCI, National Cancer Institute; Ne, neuropathy; O⁶BG, O⁶-benzylguanine; PDGF, platelet-derived growth factor; R, rash; S, somnolence; TS, thymidylate synthase.