riociguat
Bayer Inc. announced today that the Health Canada has approved the drug Adempas (riociguat) for the treatment of inoperable, or persistent and recurrent chronic thromboembolic pulmonary hypertension (CTEPH) after surgery in adult patients. Learn more…http://www.dddmag.com/news/2013/09/health-canada-approves-bayers-hypertension-drug?et_cid=3497158&et_rid=523035093&type=headline
The bark of Nauclea latifolia contains tramadol at medicinal concentrations © imagebroker / Alamy
http://www.rsc.org/chemistryworld/2013/09/african-plant-natural-source-tramadol
In another example of nature beating chemists, the African plant Nauclea latifolia has been found to be a natural source of the synthetic opioid tramadol. First marketed in 1977, tramadol is frequently used to relive moderate to moderately-severe pain. While other synthetic drugs have later been found in nature, this is the first instance where the discovery involves clinically viable concentrations.
Colloquially known as the ‘African peach’ or ‘pin cushion tree’, N. latifolia is a flowering, sub-Saharan evergreen that grows widely across Central and West Africa and is used by local populations to treat a wide variety of ailments – including epilepsy, malaria, general pain and many infectious diseases………………………. READ ALL AT
http://www.rsc.org/chemistryworld/2013/09/african-plant-natural-source-tramadol
tramadol
tramadol hydrocloride
The chemical name for tramadol hydrochloride is (±)cis-2-[(dimethylamino)methyl]-1-(3methoxyphenyl) cyclohexanol hydrochloride
Tramadol (marketed as the hydrochloride salt by Janssen Pharmaceutica as Ultram in the United States, Ralivia by Biovail in Canada and many other companies throughout the world) is a centrally acting synthetic opioid analgesic used to treat moderate to moderately severe pain. The drug has a wide range of applications, including treatment of rheumatoid arthritis, restless legs syndrome, motor neurone disease and fibromyalgia.[citation needed] It was launched and marketed as Tramal by the German pharmaceutical company Grünenthal GmbH in 1977.
Tramadol is a weak μ-opioid receptor agonist, a serotonin releaser and a reuptake inhibitor of norepinephrine. Tramadol is metabolized to O-desmethyltramadol, a significantly more potent μ-opioid agonist. Tramadol and its major metabolite(s) are distinguished from other more potent opioid agonists by relative selectivity for μ-opioid receptors.
Structurally, tramadol closely resembles a stripped down version of codeine. Both codeine and tramadol share the 3-methyl ether group, and both compounds are metabolized along the same hepatic pathway and mechanism to the stronger opioid, phenol agonist analogs. For codeine, this is morphine, and for tramadol, it is the O-desmethyltramadol.
When administered through IV, patients notice very little clinical difference in subjective potency compared to morphine.
Structurally, tapentadol is the closest chemical relative of tramadol in clinical use. Tapentadol is also an opioid, but unlike both tramadol and venlafaxine, tapentadol represents only one stereoisomer and is the weaker of the two, in terms of opioid effect. Both tramadol and venlafaxine are racemic mixtures. Structurally, tapentadol also differs from tramadol in being a phenol, and not an ether. Also, both tramadol and venlafaxine incorporate a cyclohexyl moiety, attached directly to the aromatic, while tapentadol lacks this feature.
-Tramadol.svg)
-Tramadol_gespiegelt.svg)
(1R,2R)-Tramadol (1S,2S)-Tramadol
-Tramadol.svg)
-Tramadol_gespiegelt.svg)
(1R,2S)-Tramadol (1S,2R)-Tramadol
The chemical synthesis of tramadol is described in the literature.[62] Tramadol [2-(dimethylaminomethyl)-1-(3-methoxyphenyl)cyclohexanol] has two stereogenic centers at the cyclohexane ring. Thus, 2-(dimethylaminomethyl)-1-(3-methoxyphenyl)cyclohexanol may exist in four different configurational forms:
The synthetic pathway leads to the racemate (1:1 mixture) of (1R,2R)-isomer and the (1S,2S)-isomer as the main products. Minor amounts of the racemic mixture of the (1R,2S)-isomer and the (1S,2R)-isomer are formed as well. The isolation of the (1R,2R)-isomer and the (1S,2S)-isomer from the diastereomeric minor racemate [(1R,2S)-isomer and (1S,2R)-isomer] is realized by the recrystallization of the hydrochlorides. The drug tramadol is a racemate of the hydrochlorides of the (1R,2R)-(+)- and the (1S,2S)-(–)-enantiomers. The resolution of the racemate [(1R,2R)-(+)-isomer / (1S,2S)-(–)-isomer] was described[63] employing (R)-(–)- or (S)-(+)-mandelic acid. This process does not find industrial application, since tramadol is used as a racemate, despite known different physiological effects[64] of the (1R,2R)- and (1S,2S)-isomers, because the racemate showed higher analgesic activity than either enantiomer in animals[65] and in humans.[66]
capecitabine
154361-50-9
pentyl [1-(3,4-dihydroxy-5-methyltetrahydrofuran-2-yl)-5-fluoro-2-oxo-1H-pyrimidin-4-yl]carbamate
MONDAY Sept. 16, 2013 — The first generic version of the oral chemotherapy drug Xeloda (capecitabine) has been approved by the U.S. Food and Drug Administration to treat cancers of the colon/rectum or breast, the agency said Monday in a news release.
This year, an estimated 142,820 people will be diagnosed with cancer of the colon/rectum, and 50,830 are predicted to die from the disease, the FDA said, citing the U.S. National Cancer Institute. An estimated 232,340 women will be diagnosed with cancer of the breast this year, and some 39,620 will die from it.
The most common side effects of the drug are diarrhea, vomiting; pain, redness, swelling or sores in the mouth; fever and infection, the FDA said.
The agency stressed that approved generics have the same high quality and strength as their brand-name counterparts.
License to produce the generic drug was given to Israel-based Teva Pharmaceuticals. The brand name drug is produced by the Swiss pharma firm Roche.
Capecitabine (INN) /keɪpˈsaɪtəbiːn/ (Xeloda, Roche) is an orally-administeredchemotherapeutic agent used in the treatment of metastatic breast andcolorectal cancers. Capecitabine is a prodrug, that is enzymatically converted to 5-fluorouracil in the tumor, where it inhibits DNA synthesis and slows growth of tumor tissue. The activation of capecitabine follows a pathway with three enzymatic steps and two intermediary metabolites, 5′-deoxy-5-fluorocytidine (5′-DFCR) and 5′-deoxy-5-fluorouridine (5′-DFUR), to form 5-fluorouracil
Capecitabine is FDA-approved for:
In the UK, capecitabine is approved by the National Institute for Health and Clinical Excellence (NICE) for colon and colorectal cancer, and locally advanced or metastatic breast cancer.[1] On March 29, 2007, the European Commission approved Capecitabine, in combination with platinum-based therapy (with or without epirubicin), for the first-line treatment of advanced stomach cancer.
Capecitabine is a cancer chemotherapeutic agent that interferes with the growth of cancer cells and slows their distribution in the body. Capecitabine is used to treat breast cancer and colon or rectum cancer that has spread to other parts of the body.
Capecitabine (as brand-name Xeloda) is available in light peach 150 mg tablets and peach 500 mg tablets.
Capecitabine is an orally-administered anticancer agent widely used in the treatment of metastatic breast and colorectal cancers. Capecitabine is a ribofuranose-based nucleoside, and has the sterochemical structure of a ribofuranose having an β-oriented 5-fluorocytosine moiety at C-I position.
US Patent Nos. 5,472,949 and 5,453,497 disclose a method for preparing capecitabine by glycosylating tri-O-acetyl-5-deoxy-β-D-ribofuranose of formula I using 5-fluorocytosine to obtain cytidine of formula II; and carbamoylating and hydrolyzing the resulting compound, as shown in Reaction Scheme 1 :
Reaction Scheme 1
1
The compound of formula I employed as an intermediate in Reaction
Scheme 1 is the isomer having a β-oriented acetyl group at the 1 -position, for the reason that 5-fluorocytosine is more reactive toward the β-isomer than the α-isomer in the glycosylation reaction due to the occurrence of a significant neighboring group participation effect which takes place when the protecting group of the 2-hydroxy group is acyl.
Accordingly, β-oriented tri-O-acetyl-5-deoxy-β-D-ribofuranose (formula
I) has been regarded in the conventional art to the essential intermediate for the preparation of capecitabine. However, such a reaction gives a mixture of β- and α-isomers from which cytidine (formula II) must be isolated by an uneconomical step.
Meanwhile, US Patent No. 4,340,729 teaches a method for obtaining capecitabine by the procedure shown in Reaction Scheme 2, which comprises hydrolyzing 1-methyl-acetonide of formula III to obtain a triol of formula IV; acetylating the compound of formula IV using anhydrous acetic anhydride in pyridine to obtain a β-/α-anomeric mixture of tri-O-acetyl-5-deoxy-D-ribofuranose of formula V; conducting vacuum distillation to purify the β-/α-anomeric mixture; and isolating the β-anomer of formula I therefrom:
Reaction Scheme 2
III IV
However, the above method is also hampered by the requirement to perform an uneconomical and complicated recrystallization steps for isolating the β-anomer from the mixture of β-/α-anomers of formula V, which leads to a low yield of only about 35% to 40% (Guangyi Wang et al., J. Med. Chem., 2000, vol. 43, 2566-2574; Pothukuchi Sairam et al., Carbohydrate Research, 2003, vol. 338, 303-306; Xiangshu Fei et al., Nuclear Medicine and Biology, 2004, vol. 31, 1033-1041; and Henry M. Kissman et al., J. Am. Chem. Soc, 1957, vol. 79, 5534-5540).
Further, US Patent No. 5,476,932 discloses a method for preparing capecitabine by subjecting 5′-deoxy-5-fluorocytidine of formula VI to a reaction with pentylchloroformate to obtain the compound of formula VII having the amino group and the 2-,3-hydroxy groups protected with C5Hi1CO2 groups; and removing the hydroxy-protecting groups from the resulting compound, as shown in Reaction Scheme 3 :
Reaction Scheme 3
Vl VII 1
However, this method suffers from a high manufacturing cost and also requires several complicated steps for preparing the 5′-deoxy-5-fluorocytidine of formula VI: protecting the 2-,3-hydroxy groups; conducting a reaction thereof with 5-fluorocytosine; and deprotecting the 2-,3-hydroxy groups.
Accordingly, the present inventors have endeavored to develop an efficient method for preparing capecitabine, and have unexpectedly found an efficient, novel method for preparing highly pure capecitabine using a trialkyl carbonate intermediate, which does not require the uneconomical β-anomer isolation steps.
synthesis
more info and description
Aspects of the present invention relate to capecitabine and processes for the preparation thereof.
The drug compound having the adopted name “capecitabine” has a chemical name 5′-deoxy-5-fluoro-N-[(pentyloxy) carbonyl] cytidine and has structural formula I.
H
OH OH I
This compound is a fluoropyrimidine carbamate with antineoplastic activity. The commercial product XELODA™ tablets from Roche Pharmaceuticals contains either 150 or 500 mg of capecitabine as the active ingredient.
U.S. Patent No. 4,966,891 describes capecitabine generically and a process for the preparation thereof. It also describes pharmaceutical compositions, and methods of treating of sarcoma and fibrosarcoma. This patent also discloses the use of ethyl acetate for recrystallization of capecitabine. The overall process is summarized in Scheme I.
Scheme I
U.S. Patent No. 5,453,497 discloses a process for producing capecitabine that comprises: coupling of th-O-acetyl-5-deoxy-β-D-hbofuranose with 5- fluorocytosine to obtain 2′,3′-di-O-acetyl-5′-deoxy-5-fluorocytidine; acylating a 2′, 3′- di-O-acetyl-5′-deoxy-5-fluorocytidine with n-pentyl chloroformate to form 5′-deoxy- 2′,3′-di-O-alkylcarbonyl-5-fluoro-N-alkyloxycarbonyl cytidine, and deacylating the 2′ and 3′ positions of the carbohydrate moiety to form capecitabine. The overall process is summarized in Scheme II.
Capecitabine
Scheme Il
The preparation of capecitabine is also disclosed by N. Shimma et al., “The Design and Synthesis of a New Tumor-Selective Fluoropyrimidine Carbamate, Capecitabine,” Bioorganic & Medicinal Chemistry, Vol. 8, pp. 1697-1706 (2000). U.S. Patent No. 7,365,188 discloses a process for the production of capecitabine, comprising reacting 5-fluorocytosine with a first silylating agent in the presence of an acid catalyst under conditions sufficient to produce a first silylated compound; reacting the first silylated compound with 2,3-diprotected-5- deoxy-furanoside to produce a coupled product; reacting the coupled product with a second silylating agent to produce a second silylated product; acylating the second silylated product to produce an acylated product; and selectively removing the silyl moiety and hydroxyl protecting groups to produce capecitabine. The overall process is summarized in Scheme III. te
R: hydrocarbyl
Scheme III
Further, this patent discloses crystallization of capecitabine, using a solvent mixture of ethyl acetate and n-heptane. International Application Publication No. WO 2005/080351 A1 describes a process for the preparation of capecitabine that involves the refluxing N4– pentyloxycarbonyl-5-fluorocytosine with trimethylsiloxane, hexamethyl disilazanyl, or sodium iodide with trimethyl chlorosilane in anhydrous acetonitrile, dichloromethane, or toluene, and 5-deoxy-1 ,2,3-tri-O-acetyl-D-ribofuranose, followed by hydrolysis using ammonia/methanol to give capecitabine. The overall process is summarized in Scheme IV.
Scheme IV
International Application Publication No. WO 2007/009303 A1 discloses a method of synthesis for capecitabine, comprising reacting 5′-deoxy-5- fluorocytidine using double (trichloromethyl) carbonate in an inert organic solvent and organic alkali to introduce a protective lactone ring to the hydroxyl of the saccharide moiety; reacting the obtained compound with chloroformate in organic alkali; followed by selective hydrolysis of the sugar component hydrolytic group using an inorganic base to give capecitabine. The overall process is summarized in Scheme V.
Scheme V
Even though all the above documents collectively disclose various processes for the preparation of capecitabine, removal of process-related impurities in the final product has not been adequately addressed. Impurities in any active pharmaceutical ingredient (API) are undesirable, and, in extreme cases, might even be harmful to a patient. Furthermore, the existence of undesired as well as unknown impurities reduces the bioavailability of the API in pharmaceutical products and often decreases the stability and shelf life of a pharmaceutical dosage form.
nmr
1H NMR(CD3OD) δ 0.91(3H5 t), 1.36~1.40(4H, m), 1.41(3H, d), 1.68~1.73(2H, m), 3.72(1H, dd), 4.08(1H, dd), 4.13~4.21(3H, m), 5.7O(1H, s), 7.96(1H, d)
128196-01-0 ESCITALOPRAM
Escitalopram (also known under various trade names) is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults and children over 12 years of age with major depressive disorder and generalized anxiety disorder. Escitalopram is the (S)-stereoisomer (enantiomer) of the earlier Lundbeck drug citalopram, hence the name escitalopram. Escitalopram is noted for its high selectivity with serotonin reuptake inhibition. The similarity between escitalopram and citalopram has led to accusations of “evergreening“, an accusation that Lundbeck has rejected.[1]
Escitalopram has FDA approval for the treatment of major depressive disorder and generalized anxiety disorder in adults.[2]
Escitalopram is sometimes prescribed off-label for the treatment of other conditions: social anxiety disorder,[3] panic disorder[4]and obsessive-compulsive disorder.[5] There is some evidence favouring escitalopram over the antidepressants citalopram andfluoxetine in the first two weeks of major depression.[6] Concerns of sponsorship bias with the studies are however noted.[6] In another review escitalopram and sertraline had the highest rate of efficacy and acceptability among adults receiving treatment for major depression with second-generation antidepressants.[7]
There is some controversy over selective publishing of SSRI clinical trials.[8] A meta-analysis analyzing published as well as unpublished trials found placebos to be similarly effective to SSRIs in treating mild depression, although SSRIs were more effective than placebo in more severe cases, with the magnitude of SSRI superiority increasing with increasing depression severity.[9]
A series of randomized, double-blind trials have found Escitalopram to be more efficacious and have fewer adverse effects than Citalopram.[10][11][12][13] Meta-analysis show a “small” but statistically significant improvement in effect strength [14][15] and some dispute these findings.[16]
Cipralex brand escitalopram 10mg package and tablet sheet
Escitalopram increases intrasynaptic levels of the neurotransmitter serotonin by blocking the reuptake of the neurotransmitter into the presynaptic neuron. Of the SSRIs currently on the market, escitalopram has the highest affinity for the human serotonin transporter (SERT). The enantiomer of escitalopram ((R)-citalopram) counteracts to a certain degree the serotonin-enhancing action of escitalopram. As a result, escitalopram has been claimed to be a more potent antidepressant than citalopram, which is a mixture of escitalopram and (R)-citalopram. In order to explain this phenomenon, researchers from Lundbeck proposed that escitalopram enhances its own binding via an additional interaction with another allosteric site on the transporter.[42] Further research by the same group showed that (R)-citalopram also enhances binding of escitalopram,[43] and therefore the allosteric interaction cannot explain the observed counteracting effect. In the most recent paper, however, the same authors again reversed their findings and reported that R-citalopram decreases binding of escitalopram to the transporter.[44] Although allosteric binding of escitalopram to the serotonin transporter is of unquestionable research interest, its clinical relevance is unclear since the binding of escitalopram to the allosteric site is at least 1000 times weaker than to the primary binding site.
In vitro studies using human liver microsomes indicated that CYP3A4 and CYP2C19 are the primary isozymes involved in the N-demethylation of escitalopram. The resulting metabolites, desmethylescitalopram and didesmethylescitalopram, are significantly less active and their contribution to the overall action of escitalopram is negligible.
Escitalopram was developed in close cooperation between Lundbeck and Forest Laboratories. Its development was initiated in the summer of 1997, and the resulting new drug application was submitted to the U.S. FDA in March 2001. The short time (3.5 years) it took to develop escitalopram can be attributed to the previous extensive experience of Lundbeck and Forest with citalopram, which has similar pharmacology.[45] The FDA issued the approval of escitalopram for major depression in August 2002 and for generalized anxiety disorder in December 2003. Escitalopram can be considered an example of “evergreening“[46] (also called “lifecycle management”[47])– the long-term strategy pharmaceutical companies use in order to extend the lifetime of a drug, in this case of the citalopram franchise. Escitalopram is an enantiopure compound of theracemic mixture citalopram, used for the same indication, and for that reason it required less investment and less time to develop. Two years after escitalopram’s launch, when the patent on citalopram expired, the escitalopram sales successfully made up for the loss. On May 23, 2006, the FDA approved a generic version of escitalopram by Teva.[48]On July 14 of that year, however, the U.S. District Court of Delaware decided in favor of Lundbeck regarding the patent infringement dispute and ruled the patent on escitalopram valid.[49]
In 2006 Forest Laboratories was granted an 828 day (2 years and 3 months) extension on its US patent for escitalopram.[50] This pushed the patent expiration date from December 7, 2009 to September 14, 2011. Together with the 6-month pediatric exclusivity, the final expiration date was March 14, 2012.
Escitalopram is sold under the following brand names:
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http://www.sciencedirect.com/science/article/pii/S0040402011015249
http://www.sciencedirect.com/science/article/pii/S0040402011015249
A remarkable human clinical study published in the journal Diabetes Care, the journal of the American Diabetes Association, revealed that turmeric extract was 100% successful at preventing prediabetic patients from becoming diabetic over the course of a 9-month intervention.[1]
Performed by Thailand researchers, the study’s primary object was to assess the efficacy of curcumin, the primary polyphenol in turmeric which gives the spice its golden hue, in delaying the development of type 2 diabetes mellitus (T2DM) in a prediabetic population.http://www.greenmedinfo.com/blog/turmeric-extract-100-effective-preventing-type-2-diabetes-ada-journal-study-finds
Transthyretin, or TTR for amyloidosis
THURSDAY Aug. 29, 2013 — A new medication appears to be highly effective in combating a heredity-based form of the organ-damaging genetic disorder known as amyloidosis, according to researchers.
Amyloidosis refers to a family of more than a dozen diseases in which different types of abnormal proteins called amyloids lodge in major organs and nerves. These amyloids build up to the point that they cause damage and, ultimately, organ failure.
read all at
http://www.drugs.com/news/experimental-shows-promise-rare-genetic-disorder-47059.html
Transthyretin (TTR) is a serum and cerebrospinal fluid carrier of the thyroid hormone thyroxine (T4) and retinol-binding protein bound to retinol. This is how transthyretin gained its name, transports thyroxine and retinol. The liver secretes transthyretin into the blood, and the choroid plexus secretes TTR into thecerebrospinal fluid.
TTR was originally called prealbumin[1] (or thyroxine-binding prealbumin) because it ran faster than albumin on electrophoresis gels.
It functions in concert with two other thyroid hormone-binding proteins in the serum:
| Protein | Binding strength | Plasma concentration |
|---|---|---|
| thyroxine-binding globulin (TBG) | highest | lowest |
| transthyretin (TTR) | lower | higher |
| albumin | poorest | much higher |
In cerebrospinal fluid TTR is the primary carrier of T4. TTR also acts as a carrier ofretinol (vitamin A) through its association with retinol-binding protein (RBP) in the blood and the CSF. Less than 1% of TTR’s T4 binding sites are occupied in blood, which is taken advantage of below to prevent TTRs dissociation, misfolding and aggregation which leads to the degeneration of post-mitotic tissue.
Numerous other small molecules are known to bind in the thyroxine binding sites, including many natural products (such as resveratrol), drugs (Tafamidis,[2] or Vyndaqel, diflunisal,[3][4][5] flufenamic acid),[6] and toxins (PCB[7]).
TTR is a 55kDa homotetramer with a dimer of dimers quaternary structure that is synthesized in the liver, choroid plexus and retinal pigment epithelium for secretion into the bloodstream, cerebrospinal fluid and the eye, respectively. Each monomer is a 127-residue polypeptide rich in beta sheet structure. Association of two monomers via their edge beta-strands forms an extended beta sandwich. Further association of two of these dimers in a face-to-face fashion produces the homotetrameric structure and creates the two thyroxine binding sites per tetramer. This dimer-dimer interface, comprising the two T4 binding sites, is the weaker dimer-dimer interface and is the one the comes apart first in the process of tetramer dissociation.[8]
1-Fe..
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Pioglitazone increases the body’s sensitivity to insulin
Suspension of cheap and popular medicine reversed but will now come with new safety warnings
http://www.rsc.org/chemistryworld/2013/08/india-u-turn-diabetes-pioglitazone-drug-ban
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AUGUST 20, 2013
UK patients with a certain type of skin cancer can now get access to Roche’s once-daily pill Erivedge following its launch in the country.
Erivedge（vismodegib）胶囊
Erivedge (vismodegib) is the first medicine available in the UK for the treatment of patients with symptomatic metastatic basal cell carcinoma (BCC) or locally advanced BCC that is unsuitable for surgery or radiotherapy.
http://www.pharmatimes.com/Article/13-08-20/Roche_s_new_skin_cancer_drug_now_available_in_UK.aspx
ROCHESTER, Minn. — A new population-based study has found that patients with glioblastoma who died in 2010, after the Food and Drug Administration (FDA) approval of bevacizumab, had lived significantly longer than patients who died of the disease in 2008, prior to the conditional approval of the drug for the treatment of the deadly brain cancer. Bevacizumab is used to treat patients with certain cancers whose cancer has spread. The study appears in the journal Cancer
http://www.pharmalive.com/study-brain-cancer-survival-improved-following-fda-approval-of-avastin
-Molecular-diagram.jpg)
STR REF –http://www.kidneycancerinstitute.com/Bevacizumab.html
IN CASE U NEED TO CONTACT ME THEN MAIL ME. amcrasto@gmail.com
Bevacizumab (trade name Avastin, Genentech/Roche) is an angiogenesis inhibitor, a drug that slows the growth of new blood vessels. It is licensed to treat various cancers, including colorectal, lung, breast (outside the USA), glioblastoma (USA only), kidney and ovarian.
Bevacizumab is a humanized monoclonal antibody that inhibits vascular endothelial growth factor A (VEGF-A). VEGF-A is a chemical signal that stimulates angiogenesis in a variety of diseases, especially in cancer. Bevacizumab was the first clinically availableangiogenesis inhibitor in the United States.
Bevacizumab was approved by the U.S. Food and Drug Administration (FDA) for certainmetastatic cancers. It received its first approval in 2004, for combination use with standardchemotherapy for metastatic colon cancer.It has since been approved for use in certain lung cancers, renal cancers, and glioblastoma multiforme of the brain.
At one point bevacizumab was approved for breast cancer by the FDA, but the approval was revoked on 18 November 2011. The approval for breast cancer was revoked because, although there was evidence that it slowed progression of metastatic breast cancer, there was no evidence that it extended life or improved quality of life, and it caused adverse effects including severe high blood pressure and hemorrhaging. In 2008, the FDA gave bevacizumab provisional approval for metastatic breast cancer, subject to further studies. The FDA’s advisory panel had recommended against approval. In July 2010, after new studies failed to show a significant benefit, the FDA’s advisory panel recommended against the indication for advanced breast cancer. Genentech requested a hearing, which was granted in June 2011. The FDA ruled to withdraw the breast cancer indication in November 2011. FDA approval is required for Genentech to market a drug for that indication. Doctors may sometimes prescribe it for that indication, although insurance companies are less likely to pay for it. The drug remains approved for breast cancer use in other countries including Australia.
Clinical trials are underway for many other indications including ovarian cancer, pediatric osteosarcoma, and certain non-malignant eye diseases. In the curative setting (adjuvant therapy), clinical studies are underway in breast cancer and lung cancer.
