In the U.S., there are currently thirteen approved anti-cancer therapies with recognized antiangiogenic properties in oncology. These agents, which interrupt critical cell signaling pathways involved in tumor angiogenesis and growth, comprise three primary categories:
1) monoclonal antibodies directed against specific proangiogenic growth factors and/or their receptors; and
2) small molecule tyrosine kinase inhibitors (TKIs) of multiple proangiogenic growth factor receptors;
3) inhibitors of mTOR (mammalian target of rapamycin).
In addition, at least two other approved angiogenic agents may indirectly inhibit angiogenesis through mechanisms that are not completely understood. Finally, in the field of dermatology, there are several agents used for neoplasms of the skin.
- In combination with 5-FU-based chemotherapy as first-line and second-line treatment of mCRC.
- In combination with carboplatin and paclitaxel as first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC.
- In combination with paclitaxel as first-line treatment in patients with locally recurrent or metastatic breast cancer (Europe only).
- Second-line treatment of patients with glioblastoma following temozolomide failure.
- In combination with interferon-alfa as first-line treatment of RCC.
- In combination with chemotherapy as first-line treatment in patients with newly diagnosed, advanced ovarian cancer (Europe only).
- In combination with paclitaxel plus cisplatin or topotecan as a treatment for patients with persistent, recurrent, or metastatic cervical cancer.
- As a single agent or in combination with paclitaxel as a treatment for people with advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose cancer has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy.
- In combination with docetaxel as a treatment for people with metastatic non-small cell lung cancer whose cancer has progressed on or after platinum-based chemotherapy.
- Treatment with FOLFIRI as a therapy for people with metastatic colorectal cancer whose cancer has progressed on or after therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.
Onyx
- Treatment of advanced renal cell carcinoma.
- Treatment of unresectable hepatocellular carcinoma.
- Treatment of locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (DTC) refractory to radioactive iodine.
- Treatment of gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib mesylate.
- Progressive neuroendocrine cancerous tumors located in the pancreas that cannot be removed by surgery or that have spread to other parts of the body (metastatic).
- Late-stage (metastatic) medullary thyroid cancer in adult patients who are ineligible for surgery.
- After failure of treatment with sunitinib or sorafenib.
- Treatment of progressive neuroendocrine tumors of pancreatic origin (PNET) in patients with unresectable, locally advanced, or metastatic disease.
- Patients with subependymal giant cell astrocytoma (SEGA) who require therapeutic intervention but are not candidates for curative surgical resection.
- In combination with exemestane to treat certain postmenopausal women with advanced hormone-receptor positive, HER2-negative breast cancer.
Schering
- Treatment of multiple myeloma in combination with dexamethasone in patients who have received at least one prior therapy.
- Administered in combination with dexamethasone in patients with newly diagnosed multiple myeloma.
Additionally, in the field of dermatology, a number of FDA-approved agents have antiangiogenic properties:
- Alitretinoin (Panretin® 0.1% gel, Ligand) is a topical retinoid indicated for the treatment of AIDS-related Kaposi’s sarcoma (KS). Retinoids, derivates of vitamin A, are antiangiogenic via downregulation of VEGF.
- Imiquimod (Aldara® 5% cream, Zyclara 3.75% cream, Medicis) is a Toll-Like Receptor 7 agonist which is an immune response modifier that exerts antiangiogenic activity through local upregulation of interferons and interleukins, downregulation of FGF-2 and MMP-9, and induction of endothelial apoptosis. Imiquimod is indicated for both benign neoplasms (genital warts) and for malignant skin cancers (actinic keratosis and basal cell carcinoma).
- Polyphenon E (Veregen® 15% ointment, Bradley/MediGene) is a defined composition of polyphenolic kunecatechins extracted from green tea leaves. The major green tea catechins, epigallocatechin-3 (EGCG), inhibits VEGF expression. Polyphenon E topical ointment indicated for genital warts.
- Vismodegib (Eviredge, Genentech) is a cyclopamine-competitive antagonist of the smoothened receptor (SMO) which is part of the hedgehog signaling pathway. Vismodegib is indicated for patients with basal cell carcinoma (BCC) which has metastasized to other parts of the body, relapsed after surgery, or cannot be treated with surgery or radiation.
- Sonidegib (Odomzo, Novartis) is a Hedgehog signaling pathway inhibitor (via smoothened antagonism) indicated for locally advanced basal cell carcinoma that has recurred following surgery or radiation therapy, or who are not candidates for surgery or radiation therapy.