PONATINIB: ARIAD ASKED TO STOP PRODUCTION !

THROMBOTIC EVENTS AND POSSIBLE VASCULOPATHY MAY HAVE LED TO THE FDA ORDER TO SUSPEND REPORTEDLY THE PRODUCTION OF PONATINIB A DRUG JUST RECENTLY APPROVED IN THE TREATMENT OF CHRONIC MYELOID LEUKEMIA

Ponatinib (Iclusig, previously AP24534) is an Food and Drug Administration approved oral drug candidate developed by ARIAD Pharmaceuticals for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). It is a multi-targeted tyrosine-kinase inhibitor.^[1] Some forms of CML, those that have the T315I mutation, are resistant to current therapies such as imatinib. Ponatinib has been designed to be effective against these types of tumors.^[2]
Oncologists have complained, however, that many patients can not afford the "astronomical" cost of $138,000 a year, which makes it one of the most expensive drugs in medicine, and far more expensive than what is needed to pay the development costs.<sup>[3][4] WIKIPIDIA

THE THROMBOTIC COMPLICATION WAS NOT NEW HOWEVER, IT IS UNCLEAR WHY THE FDA MOVED TO ORDER ARIAD TO STOP THE PRODUCTION.</sup>  


"The United States Food and Drug Administration issued a partial clinical hold on new trial enrollment for Iclusig on 9 October 2013 due to an increased number of blood clots observed in patients taking the drug.^[6] The EPIC trial was later cancelled on 18 October.^{[7]"WIKIPEDIA}

NOW THE STOP ORDER IS IN EFFECT REPORTEDLY!

*T-cell therapy, that is genetically engineered T-cells, is a valid modality of cancer treatment.  Porter et al updated their finding at the ASH describing response rate in refractory CLL and ALL.  Patients were given a lentiviral vector that expressed a chimeric antigen receptor "with specificity for the B cell Antigen CD19 paired with CD137 and CD3-zeta." (hemonc today) some of the reported results where positively dramatic.
The experience with MAGE 11 for treatment refractory melanoma did not go so well.

Melanoma Antigen Gene Protein MAGE-11 Regulates Androgen Receptor 

What you pick to attack should not be in the brain (attack to the brain by T cell is likely), and involving a "crazy gene" the like of Androgen Receptor will have many unexpected consequences.  patient died with coma and seizures!   T-cell tissue penetration is bound to occur because it is what T cell do so your task is to pick the receptor carefully!

and don't go out there and pick p300, a potent and ubiquitous transcriptional regulator, because it is Ubiquitous!  Tissue specificity as done above in Hematologic malignancies would be more appropriate!
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NOW A BIT OF GOOD NEWS

Infusion of Autologous dendritic cell Immunotherapy  (AGS-003) given with SUNITINIB extended survival in Metastatic Renal cell cancer!   Think Immunotherapy when the going get tough we told recently... congrats to NC researcher to have proven the point!   Follow this principle in tough Myeloma cases.  May be drendritic cell infusion will work in Myeloma!

Secondary Hematologic Malignancies

Japanese researchers suggested in a retrospective study of patients treated with Temodar for Glioma, that there is an increased occurrence of secondary Myelodysplasia, leukemias and particularly Acute Lymphoblastic Leukemia.  It is interesting to look further, beyond the simple observation and speculate as to what leads to such a transformation at the gene level.
Leukemias are a disease not only of pathways, but of deep derangement at the Histone-DNA level and include particularly not only protein complexes similar to core binding factors, but also regulator genes which appear to be specifically amplified in leukemias!
It is pertinent to also look closer at Proteins Kinases affecting or interacting with DNA.  Temodar is an Alkylating agent per the researcher's report.
The interval between the treatment and the occurrence is also interesting, and suggests that the secondary Leukemia results from a secondary amplification of proliferative genes after the onslaught on cellular receptors by the chemical stimulus. The NK-kB, c-JUN must be in play.  Blocking these pathways could prevent such malignant occurrence. We will soon find that secondary malignancy could be prevented by simply blocking some tumor growth factors.  We don't need to accept these complications any more.  I learned that my first patient who was diagnosed with Hodgkin disease, a curable disease, died later on with an Acute Leukemia.  She was free of Hodgkin disease. Our current follow-up is inadequate in this regard, as we sit and wait for secondary leukemia to set in.  Lets look into blocking Tumor growth factors to stop secondary leukemias!

DRUGS IN THE PIPELINE PER "ONCOLOGY LIVE"

1. POMALIDOMIDE APPROVED FOR CML (EVEN T315I POSITIVE),  A.L.L.   PHILADELPHIA POSITIVE

2.T-DM 1 FOR HER-2 POSITIVE BREAST CANCERS.

3.APF530   FOR ACUTE AND DELAYED CHEMOTHERAPY INDUCED VOMITING

4 LYMPHOSEEK, TECHNETIUM, WILL SEEK SENTINEL NODES 

5. CHEMOSAT FOR OCULAR MELANOMA METASTATIC TP THE LIVER, MELPHALAN BASED

6. TIVOZANIB ANTI-VEGF FOR METASTATIC RENAL CANCERS

7 AFATINIB  FOR ADVANCED LUNG CANCER EGFR, ERB4 INHIBITOR

8. DABRAFENIB ANTI-BRAF IN MELANOMA

9. TRAMETINIB -ANTI MEK FOR ADVANCED MELANOMA

10 RADIUM-223 DICHLORIDE ALPHA PARTICLE EMISSION,  IN BONE METASTASIS IN PROSTATE CANCER