Anticancer carrier-linked prodrugs in clinical trials

被引：75

作者：

Kratz, Felix ^{[1
]}

Abu Ajaj, Khalid ^{[1
]}

Warnecke, Andre ^{[1
]}

机构：

[1] Tumor Biol Ctr, Macromol Prodrugs, D-79106 Freiburg, Germany

来源：

EXPERT OPINION ON INVESTIGATIONAL DRUGS | 2007年 / 16卷 / 07期

关键词：

antibodies; anticancer prodrugs; cancer chemotherapy; drug targeting; polymer therapeutics;

D O I：

10.1517/13543784.16.7.1037

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Coupling of low molecular weight anticancer drugs to antibodies, serum proteins or polymers through a cleavable linker has been an effective method for improving the therapeutic index of cytotoxic established agents. Modern drug-antibody conjugates that have recently entered clinical trials have primarily used highly potent drugs such as calicheamicin or maytansins. Gemtuzumab ozogamicin, a conjugate of calicheamicin and an anti-CD33 humanized antibody, is the first drug-antibody conjugate to receive market approval. Drug conjugates that have undergone clinical assessment include N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates with doxorubicin, camptothecin, paclitaxel and Pt(II) complexes, poly(ethylene glycol) conjugates with camptothecin and paclitaxel, polyglutamate conjugates with paclitaxel and camptothecin, a methotrexate-albumin conjugate and an albumin-binding doxorubicin prodrug. This review summarizes the Phase I - III studies that have been performed with these macromolecular prodrugs.

引用

页码：1037 / 1058

页数：22

共 82 条

[61] Synthesis and characterization of AP5346, a novel polymer-linked diaminocyclohexyl platinum chemotherapeutic agent [J].

Sood, Paul ;

Thurmond, K. Bruce, II ;

Jacob, Jeremy E. ;

Waller, Lynda K. ;

Silva, George O. ;

Stewart, Donald R. ;

Nowotnik, David P. .

BIOCONJUGATE CHEMISTRY, 2006, 17 (05) :1270-1279

[62] Pharmacokinetics of methotrexate-albumin conjugates in tumor-bearing rats [J].

Stehle, G ;

Wunder, A ;

Sinn, H ;

Schrenk, HH ;

Schutt, S ;

Frei, E ;

Hartung, G ;

MaierBorst, W ;

Heene, DL .

ANTI-CANCER DRUGS, 1997, 8 (09) :835-844

[63]

Stehle G, 1997, ANTI-CANCER DRUG, V8, P677

[64]

TANNOCK IF, 1989, CANCER RES, V49, P4373

[65] Cytotoxic activity of the maytansinoid immunoconjugate B-B4-DM1 against CD138+ multiple myeloma cells [J].

Tassone, P ;

Goldmacher, VS ;

Neri, P ;

Gozzini, A ;

Shammas, MA ;

Whiteman, KR ;

Hylander-Gans, LL ;

Carrasco, DR ;

Hideshima, T ;

Shringarpure, R ;

Shi, JL ;

Allam, CK ;

Wijdenes, J ;

Venuta, S ;

Munshi, NC ;

Anderson, KC .

BLOOD, 2004, 104 (12) :3688-3696

[66] Phase I clinical and pharmacokinetic study of PNU166945, a novel water-soluble polymer-conjugated prodrug of paclitaxel [J].

Terwogt, JMM ;

Huinink, WWT ;

Schellens, JHM ;

Schot, M ;

Mandjes, IAM ;

Zurlo, MG ;

Rocchetti, M ;

Rosing, H ;

Koopman, FJ ;

Beijnen, JH .

ANTI-CANCER DRUGS, 2001, 12 (04) :315-323

[67] Randomized phase II study of BR96-doxorubicin conjugate in patients with metastatic breast cancer [J].

Tolcher, AW ;

Sugarman, S ;

Gelmon, KA ;

Cohen, R ;

Saleh, M ;

Isaacs, C ;

Young, L ;

Healey, D ;

Onetto, N ;

Slichenmyer, W .

JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (02) :478-484

[68] Cantuzumab mertansine, a maytansinoid immunoconjugate directed to the CanAg antigen: A phase I, pharmacokinetic, and biologic correlative study [J].

Tolcher, AW ;

Ochoa, L ;

Hammond, LA ;

Patnaik, A ;

Edwards, T ;

Takimoto, C ;

Smith, L ;

de Bono, J ;

Schwartz, G ;

Mays, T ;

Jonak, ZL ;

Johnson, R ;

DeWitte, M ;

Martino, H ;

Audette, C ;

Maes, K ;

Chari, RVJ ;

Lambert, JM ;

Rowinsky, EK .

JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (02) :211-222

[69] CURE OF XENOGRAFTED HUMAN CARCINOMAS BY BR96-DOXORUBICIN IMMUNOCONJUGATES [J].

TRAIL, PA ;

WILLNER, D ;

LASCH, SJ ;

HENDERSON, AJ ;

HOFSTEAD, S ;

CASAZZA, AM ;

FIRESTONE, RA ;

HELLSTROM, I ;

HELLSTROM, KE .

SCIENCE, 1993, 261 (5118) :212-215

[70]

Trail PA, 1997, CANCER RES, V57, P100

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