Particles of paclitaxel and albumin in combination with bevacizumab against cancer
A nanoparticle, bevacizumab technology, applied in peptide/protein components, antibodies, drug combinations, etc., can solve problems such as affecting albumin transport
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Embodiment 1
[0268] Example 1. Administered every three weeks In Phase III studies, compared to improved response and reduced toxicity
[0269] [000237] Significantly lower rates of neutropenia and hypersensitivity reactions, no need for steroid premedication, shorter duration of neuropathy, shorter infusion times, and higher doses.
[0270] [000238] In individuals with metastatic breast cancer (MBC), ABI-007 - the first biologically interacting nab-paclitaxel in the form of nanoparticles without any solvent, and based on Paclitaxel Compare. This Phase III study was conducted to corroborate preclinical studies demonstrating that ABI-007 interacts with Superior efficacy and reduced toxicity compared to Subjects were randomized to a 3-week cycle or ABI-007 260mg / m administered (iv) over a 30-minute period 2 Without predosing (n=229), or given intravenously over a 3-hour period 175mg / m 2 , predosed (n=225). and In contrast, ABI-007 showed a significantly higher response r...
Embodiment 2
[0271] Example 2. In individuals with taxane-refractory metastatic breast cancer, weekly dosing
[0272] [000239] A recent phase II clinical study showed that in individuals with metastatic breast cancer, at a dose of 125 mg / m 2 give weekly (nanoparticle albumin-bound paclitaxel) produces long-term disease control, the patient's disease in the application or Progression despite treatment (ie, the individual is taxane refractory).
[0273] 【000240】 Believed to represent the first biologically interacting composition utilizing a receptor-mediated (gp60) pathway found to be integral to obtaining high intracellular tumor concentrations of the active ingredient, paclitaxel. The phase II study included 75 individuals with taxane-refractory metastatic breast cancer. 125mg / m per week 2 Administered by 30-minute infusion No preadministration of steroids / antihistamines or G-CSF prophylaxis. Subjects received three weekly doses followed by 1 week off, repeated every 28 day...
Embodiment 3
[0281] Example 3. In MDA-MB-435 human tumor xenografts, (ABI-007) synergizes with targeted anti-angiogenic pro-apoptotic peptide (HKP)
[0282][000248] The anti-angiogenic activity of a small synthetic pro-apoptotic peptide consisting of two functional domains has been reported, one targeting the CD 13 receptor (aminopeptidase N) on tumor microvessels and the other functional Domain interferes with mitochondrial membranes after internalization. See, Nat Med. 1999 Sep;5(9):1032-8. Discovery of the second generation dimer peptide CNGRC-GG-d(KLAKLAK) 2 ——Named as HKP (Hunter Killer Peptide), it has improved anti-tumor activity. Due to anti-angiogenic agents such as Exhibiting synergy with cytotoxic agents such as 5-fluorouracil, we evaluated the anti-angiogenic agents HKP and (ABI-007) in combination, Paclitaxel, an albumin nanoparticle, is transported by gp60 receptors in the vascular endothelium (Desai, SABCS 2003).
[0283] [000249] method: with an average tumor vol...
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