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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/12/29 15:42:23」(JST)

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The structure of HER2 and pertuzumab

Pertuzumab (also called 2C4, trade name Perjeta) is a monoclonal antibody marketed by Genentech for the treatment of HER2-positive breast cancer, in combination with trastuzumab and docetaxel.^[1] The first of its class in a line of agents called "HER dimerization inhibitors". By binding to HER2, it inhibits the dimerization of HER2 with other HER receptors, which is hypothesized to result in slowed tumor growth.^[2] Pertuzumab received US FDA approval for the treatment of HER2-positive metastatic breast cancer on June 8, 2012.^[3] Pertuzumab was developed at Genentech and is now owned by Roche which acquired Genentech in 2009.

Clinical trials[edit]

Early clinical trials of pertuzumab in prostate, breast, and ovarian cancers met with limited success.^[4]

The dosage of pertuzumab used in the pivotal phase III CLEOPATRA (Clinical Evaluation of Pertuzumab and Trastuzumab) trial was as follows: IV 840 mg loading dose followed by IV 420 mg every three weeks.^[5]

The pharmacokinetics of intravenous pertuzumab appear to be unaffected by age and no drug-drug interaction has been reported with docetaxel. The pharmacokinetics and pharmacodynamics of pertuzumab were summarized in a Feb 2012 review by Gillian Keating.^[5]

The combination of pertuzumab plus trastuzumab plus docetaxel, as compared with placebo plus trastuzumab plus docetaxel, when used as first-line treatment for HER2-positive metastatic breast cancer, significantly prolonged progression-free survival, with no increase in cardiac toxic effects in the randomized, double-blind, multinational, phase III CLEOPATRA trial.^[5]

Intravenous pertuzumab is currently being evaluated in patients with breast cancer in the following trials: MARIANNE (advanced breast cancer), NEOSPHERE (early breast cancer), TRYPHAENA (HER2-positive stage II/III breast cancer) and APHINITY (HER2-positive nonmetastatic breast cancer).^[5]

References[edit]

^ http://www.gene.com/download/pdf/perjeta_prescribing.pdf
^ de Bono, Johann S.; Bellmunt, J; Attard, G; Droz, JP; Miller, K; Flechon, A; Sternberg, C; Parker, C et al. (20 January 2007). "Open-Label Phase II Study Evaluating the Efficacy and Safety of Two Doses of Pertuzumab in Castrate Chemotherapy-Naive Patients With Hormone-Refractory Prostate Cancer". Journal of Clinical Oncology 25 (3): 257–262. doi:10.1200/JCO.2006.07.0888. PMID 17235043. |displayauthors= suggested (help)
^ "FDA Approves Perjeta (Pertuzumab) for People With HER2-Positive Metastatic Breast Cancer" (Press release). Genentech. Retrieved 2012-06-09.
^ Genentech press release - May 15, 2005
^ ^a ^b ^c ^d Keating GM. Pertuzumab: in the first-line treatment of HER2-positive metastatic breast cancer. Drugs 2012 Feb 12; 72 (3): 353-60.Link text

External links[edit]

PERJETA™ (pertuzumab) HER2/neu receptor antagonist

10.1056/NEJMoa1113216

UpToDate Contents

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1. 乳癌に対する術前補助化学療法：理論的根拠、治療前評価、および治療法の選択肢 neoadjuvant therapy for breast cancer rationale pretreatment evaluation and therapeutic options
2. 成人における抗癌剤の投与 dosing of anticancer agents in adults
3. HER2陽性転移性乳癌の全身治療 systemic treatment for her2 positive metastatic breast cancer
4. トラスツズマブおよびその他の抗HER2薬の心毒性 cardiotoxicity of trastuzumab and other her2 targeted agents
5. 乳癌の治療プロトコル treatment protocols for breast cancer

English Journal

Effects of a human compact anti-ErbB2 antibody on prostate cancer.

Malara AE, Fedele C, Aloj L, Arra C, Laccetti P, D'Alessio G, De Lorenzo C.SourceDepartment of Structural and Functional Biology, University of Naples Federico II, I-80126 Naples, Italy.
Oncology reports.Oncol Rep.2012 Jul;28(1):297-302. doi: 10.3892/or.2012.1760. Epub 2012 Apr 10.
Prostate cancer is the most commonly diagnosed malignancy in men in developed countries. ErbB2, a tyrosine kinase receptor overexpressed in many human cancer types, contributes to prostate cancer progression by activating the androgen receptor in a steroid poor en
PMID 22505344

Pertuzumab monotherapy after trastuzumab-based treatment and subsequent reintroduction of trastuzumab: activity and tolerability in patients with advanced human epidermal growth factor receptor 2-positive breast cancer.

Cortés J, Fumoleau P, Bianchi GV, Petrella TM, Gelmon K, Pivot X, Verma S, Albanell J, Conte P, Lluch A, Salvagni S, Servent V, Gianni L, Scaltriti M, Ross GA, Dixon J, Szado T, Baselga J.SourceMassachusetts General Hospital Cancer Center, 55 Fruit St, Lawrence House 108, Boston, MA 02114; jbaselga@partners.org.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology.J Clin Oncol.2012 May 10;30(14):1594-600. Epub 2012 Mar 5.
PURPOSE The combination of pertuzumab and trastuzumab resulted in a clinical benefit rate (CBR) of 50% in patients with human epidermal growth factor receptor 2 (HER2) -positive breast cancer whose disease progressed during prior trastuzumab-based therapy. To define whether this previously observed
PMID 22393084

Japanese Journal

新規HER2阻害剤--TDM1,pertuzumabを中心に (特集新しい作用機序の分子標的薬剤)

青儀健二郎
腫瘍内科 7(5), 393-397, 2011-05
NAID 40018890363

Enhancement of paclitaxel-induced apoptosis in HER2-overexpressing human breast cancer cells by a pertuzumab mimetic peptide, HRAP(MEDICAL BIOTECHNOLOGY)

Nakajima Hiroo,Mizuta Naruhiko,Sakaguchi Koichi,Fujiwara Ikuya,Yoshimori Atsushi,Magae Junji,Tanuma Sei-ichi
Journal of bioscience and bioengineering 110(2), 250-253, 2010-08
… HRAP, a pentapeptide designed to bind with the pertuzumab interacting site in an extracellular domain of the HER2 molecule, enhanced the cytotoxicity of paclitaxel in HER2-overexpressing human breast cancer cell lines, BT474 and SKBR-3, but not in MDA-231 cells, which express lower levels of HER2. …
NAID 110007700577

Related Pictures

Pertuzumab gets FDA approval Mode of action of pertuzumab (simplified Fig. 1. of the structures of pertuzumab Pertuzumab (Perjeta) packaging Protein therapeutics: new applications for action du pertuzumab et du trastuzumab

★リンクテーブル★

リンク元	「mab」「ペルツズマブ」

「mab」

Pertuzumab ^?
Monoclonal antibody
Type	Whole antibody
Source	Humanized (from mouse)
Target	HER2
Clinical data
Trade names	Perjeta; Omnitarg
Licence data	US FDA:link
Pregnancy cat.	D (US)
Legal status	℞-only (US)
Routes	Intravenous
Identifiers
CAS number	380610-27-5
ATC code	L01XC13
UNII	K16AIQ8CTM
KEGG	D05446
ChEMBL	CHEMBL2007641
Chemical data
Formula	?
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