Drug intelligence / Profile preview

rh-endostatin + carboplatin + pemetrexed

Development stage
Phase 4
Lead developer
Simcere Pharmaceutical Group
Modality
Classical Binding Small Molecules → Small Molecules, Covalent Small Molecules → Small Molecules, Nucleic Acid-Directed Small Molecules → Small Molecules
Administration
Intravenous
01

Overview

This combination therapy consists of recombinant human endostatin (rh-endostatin, also known as Endostar) combined with the chemotherapy agents carboplatin and pemetrexed. It's primarily used in the treatment of non-small cell lung cancer (NSCLC). ## Mechanism of Action The combination works through multiple mechanisms: 1. **Rh-endostatin (Endostar)** is an anti-angiogenic agent that directly targets new capillary endothelial cells around tumors. It's a C-terminal fragment type of XVIII collagen that inhibits neovascularization[1][3]. Rh-endostatin can remodel and normalize tumor blood vessels, which improves the hypoxic condition in tumors and increases the concentration of other drugs inside tumor tissues[2]. 2. **Pemetrexed** (Alimta) is a chemotherapy drug that destroys quickly dividing cells, such as cancer cells[5]. 3. **Carboplatin** is another chemotherapy drug that also targets rapidly dividing cells[5]. ## Clinical Evidence Studies have shown that adding rh-endostatin to chemotherapy regimens can improve outcomes in NSCLC patients: - Extended use of rh-endostatin (≥4 cycles) with platinum-based chemotherapy has been associated with significantly better progression-free survival (PFS) and overall survival (OS) in advanced NSCLC patients[3]. - When combined with pemetrexed/cisplatin, rh-endostatin showed a trend of improved PFS in maintenance therapy for NSCLC patients, though it did not significantly prolong PFS or OS in first-line treatment compared to pemetrexed/cisplatin alone[1]. - A phase II clinical study in extensive small cell lung cancer (SCLC) patients showed promising results with rh-endostatin plus chemotherapy (etoposide plus cisplatin), with median PFS and OS of 5 and 11.5 months, respectively[2]. ## Administration The treatment is typically administered as follows: - Pemetrexed is given as an intravenous drip over 10 minutes - Carboplatin is administered as an intravenous drip over 15 to 60 minutes - Rh-endostatin is given intravenously Treatment cycles usually last 3 weeks (21 days), and patients might receive 4 to 6 cycles over approximately 4 months[5]. To reduce side effects of pemetrexed, patients may also receive: - Folic acid tablets starting at least 5 days before treatment - Vitamin B12 injections - Steroid tablets[5] ## Safety Profile The combination therapy has shown acceptable toxicity profiles. Common side effects associated with rh-endostatin include fever, rash, dizziness, headache, diarrhea, fatigue, palpitation, and chest discomfort[1]. Studies have indicated that extended use of rh-endostatin (≥4 cycles) provides additional survival benefits with satisfactory toxicity profiles[3]. This combination represents an important treatment option for advanced NSCLC patients, particularly those without driver gene mutations who may benefit from the anti-angiogenic effects of rh-endostatin alongside traditional chemotherapy.

Brand names
Endostar
Other names
recombinant human endostatin, carboplatin, pemetrexed combination
02

Targets

DNADHFR (Dihydrofolate reductase)GART (GAR transformylase)GPC (Lassa virus glycoprotein complex)NCL (Nucleolin)TS (Thymidylate synthase)VEGFR2 (Vascular endothelial growth factor receptor 2)ITGA5:ITGB1 (Integrin α5β1)

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