A Phase IB Trial of Intravenous INO-1001 Plus Oral Temozolomide in Subjects with Unresectable Stage-III or IV Melanoma

被引：58

作者：

Bedikian, Agop Y. ^{[1
]}

Papadopoulos, Nicholas E.

Kim, Kevin B.

Hwu, Wen-Jen

Homsi, Jade

Glass, Michelle R.

Cain, Suzanne

Rudewicz, Patrick ^{[2
]}

Vernillet, Laurent ^{[2
]}

Hwu, Patrick

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Unit 430, Houston, TX 77030 USA

[2] Genentech Inc, San Francisco, CA 94080 USA

来源：

CANCER INVESTIGATION | 2009年 / 27卷 / 07期

关键词：

Temozolomide; INO-1001; PARP inhibitor; Pharmacokinetics; Melanoma; MISMATCH REPAIR-DEFICIENT; ANTITUMOR-ACTIVITY; POLY(ADP-RIBOSE); INHIBITOR; GLIOMA; RESISTANCE; INCREASES; CHEMOPOTENTIATION; ALKYLTRANSFERASE; CYTOTOXICITY;

D O I：

10.1080/07357900802709159

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

INO-1001 is a PARP-1 inhibitor that interrupts the repair process of N-methylpurines generated by temozolomide. We evaluated the pharmacokinetics of INO-1001 and determined its safety when used with temozolomide at 200 mg/m2/day x 5 days every 4 weeks. We enrolled 12 adult patients, in cohorts of 3-6 patients, into the study. INO-1001 at doses of 100, 200 and 400 mg was given intravenous for 1 hr q 12 hr for 10 doses. INO-1001 had a moderate clearance, volume of distribution and a relatively short terminal half-life. Myelosuppression and elevation of liver transaminases were dose-limiting toxicities (DLTs) of INO-1001 at 400 mg.

引用

页码：756 / 763

页数：8

共 27 条

[21]

SAM WJ, 2006, P AM ASSOC CANC RES, V47, pA2914

[22]

Spiro T, 2000, Forum (Genova), V10, P274

[23]

Tentori L, 2003, CLIN CANCER RES, V9, P5370

[24] Inhibition of telomerase increases resistance of melanoma cells to temozolomide, but not to temozolomide combined with poly (ADP-ribose) polymerase inhibitor [J].

Tentori, L ;

Portarena, I ;

Barbarino, M ;

Balduzzi, A ;

Levati, L ;

Vergati, M ;

Biroccio, A ;

Gold, B ;

Lombardi, ML ;

Graziani, G .

MOLECULAR PHARMACOLOGY, 2003, 63 (01) :192-202

[25] Poly (ADP-ribose) polymerase inhibitor increases growth inhibition and reduces G2/M cell accumulation induced by temozolomide in malignant glioma cells [J].

Tentori, L ;

Portarena, I ;

Torino, F ;

Scerrati, M ;

Navarra, P ;

Graziani, G .

GLIA, 2002, 40 (01) :44-54

[26] Combined treatment with temozolomide and poly(ADP-ribose) polymerase inhibitor enhances survival of mice bearing hematologic malignancy at the central nervous system site [J].

Tentori, L ;

Leonetti, C ;

Scarsella, M ;

d'Amati, G ;

Portarena, I ;

Zupi, G ;

Bonmassar, E ;

Graziani, G .

BLOOD, 2002, 99 (06) :2241-2244

[27] Pharmacological strategies to increase the antitumor activity of methylating agents [J].

Tentori, L ;

Graziani, G .

CURRENT MEDICINAL CHEMISTRY, 2002, 9 (13) :1285-1301

← 1 2 3 →