Optimizing Chemotherapy:It is important to note that standard cancer treatments (surgery, chemo/radiation) can always beop...
Based on cytogenetic and immune based data, patients with an abnormal 3q chromosome mostlikely have the MEL1S fusion prote...
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Optimizing Chemotherapy

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It is important to note that standard cancer treatments (surgery, chemo/radiation) can always be optimized and improved and many examples exist of life enhancing advancements for almost every type of cancer.

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Optimizing Chemotherapy

  1. 1. Optimizing Chemotherapy:It is important to note that standard cancer treatments (surgery, chemo/radiation) can always beoptimized and improved and many examples exist of life enhancing advancements for almostevery type of cancer.Since the genetic subtypes of each cancer usually have varying prognoses and responses totreatment, so it is important to determine the specific subtype for each patient. The subtypes ofmost cancers are determined by the types of cell surface proteins (immunophenotyping) and thechromosomal changes (translocations).Therefore, it is fundamental that the treatment you engage in is optimized for your particularmolecular signature and not just the most common form of treatment available in your area.The following section shows how the standard treatment for Acute Myeloid Leukemia can beoptimized.The Five-year survival for standard AML treatment with 7+3 (cytarabine & daunorubicin) variesfrom 15-70% and relapse rates vary from 78-33%, depending on the genetic subtype (Grimwadeet al. (1998).The effectiveness the standard treatment (referred to as 7+3) has on patients with specific geneticsignatures is indicated below.The prognostic chromosomal rearrangements for standard treatment of AML (7+3) are asfollows:Good Prognosis:AML cases with chromosomal rearrangements such as t(8;21), t(15;17), inv(16) have a five yearsurvival rate of 70% and a relapse rate of 33%.Intermediate Prognosis:AML cases with chromosomal rearrangements such as normal, +8, +21, +22, del(7q), del(9q) orabnormal 11q23, have a five year survival rate of 48% and a relapse rate of 50%.Poor Prognosis:AML cases with chromosomal rearrangements such as -5, -7, del(5q), abnormal 3q or complexcytogenetics, have a five year survival rate of 15% and a relapse rate of 78%As you can see, the outlook for patients with poor prognosis rearrangements is not good.The next section outlines a significant improvement in treating these patients.Concerns with Standard Treatment for AML Patients Harboring Abnormal Chromosome3q:Genetically, AML is a heterogeneous disease with 40% of cases based on primary chromosometranslocations or inversions that encode fusion proteins (Shing et al., 2007).
  2. 2. Based on cytogenetic and immune based data, patients with an abnormal 3q chromosome mostlikely have the MEL1S fusion protein driving their disease. The loss of the p53 tumor suppressorgene usually accompanies this genetic rearrangement. Since the standard treatment was notdesigned to target cells expressing this fusion protein, it is unlikely to achieve remission in thiscase.Furthermore, the 7+3 regime is only effective when the chemotherapeutic agents are combined ina specific ratio. Since the genes that metabolize these agents as well as individual patients healthvaries greatly, maintaining this narrow therapeutic window is challenging.Improvements to Treatment for AML (Optimized Chemotherapy):In CPX-351,cytarabine and daunorubicin are encapsulated within liposomes in a 5:1 ratio,allowing for the synergistic drug ratio to be maintained in the blood plasma for 24 hours post-injection, which is a significant improvement.Results from pre-clinical studies have shown that despite using sub-MTD daunorubicin doses,CPX-351 exhibited superior therapeutic activity, maintenance of synergistic drug ratios in bonemarrow, and high proportions of long-term survivors compared to standard free-drug cocktails(Lim et al., 2010).Significance:The significance of this example is that it indicates how a simple variation in a commonprocedure, such as maintaining a synergistic 5:1 drug ratio, results in superior therapeuticactivity, maintenance of synergistic drug ratios in bone marrow, and high proportions of long-term survivors compared to standard free-drug cocktails.While this variation may not appear significant in long-term management of AML, it isimportant to note that with every therapeutic approach and type of cancer examined, we haveidentified many similar examples of life enhancing updates and improvements.If you have AML and are interested in receiving CPX-351, click on the following link tocontact Celator:http://www.celatorpharma.com/new/products_cpx351.html

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