New Drugs and Therapies at the Forefront of treatment for Acute Lymphoblastic Leukemia

J.R.Stokes Illustrations: Natural Killer: T-cell vs. Leukemia
J.R.Stokes Illustrations: Natural Killer: T-cell vs. Leukemia

Researchers received encouraging news on March 22, 2012, with the information that the novel drug to treat acute lymphoblastic leukemia, known as Marqibo won an FDA panel vote. The group of oncology advisers voted 7-4 endorsing the Vincristine Sulfate CAS# 2068-78-2 liposomal injection, also known as the brand Marqibo®, for treatment of ALL. The patients participating in this particular study had a rare form of ALL, and multiple therapeutic attempts had been deemed unsuccessful for them. Of the 65 patients in the single-arm study, 20% experienced a complete or nearly complete response, with a median duration of 5.4 months, and an overall 7.7 month survival rate. This news is the latest in several galvanizing reports released regarding new and innovative treatments for acute lymphoblastic leukemia. In addition to evidence that significant gains have been made in ALL survival rates in children, reports of unique approaches to care using Theranostics have surfaced as well.

Promising news for families with children suffering from acute lymphoblastic leukemia or ALL, was published in Reuters Health on March 16, 2012. Results were released from a study conducted at the University of Colorado School of Medicine and Children’s Hospital, which revealed significant gains in the fight against childhood leukemia have been made. Data gleaned from this study showed that out 20,000 babies, children and adolescents who had ALL, the survival rate of at least five years after the initial diagnosis increased, from 84% in the early 1990’s to 90% a decade later (Figure 1).

Figure 1. Survival rate of 20,000 patients with ALL 5 years after initial diagnosis



This research is hopeful, especially considering the fact that 98% of childhood leukemias are classified as acute lymphocytic leukemia. In addition, 25% of all childhood cancers are leukemia, which amount to roughly 2,200 American children each year. As a cancer of the bone marrow and blood, the child with leukemia has bone marrow which begins to make blood cells that don’t mature properly. These immature cells continue to reproduce, thus crowding out the healthy cells. Effective treatment is not only crucial, it is also completely within reach for scientists today. Only fifty years ago childhood leukemia was considered an incurable disease, and literally all children affected by it did not survive. Drug treatments for ALL are varied, and include cyclophosphamide, which is an alkylating agent;  methotrexate, which is an antimetabolite, and  daunorubicin, classified as both an antibiotic and antineoplastic.

Dr. Stephen Hunger and colleagues, from the University of Colorado School of Medicine and Children’s Hospital in Colorado, reported encouraging results from the Children’s Oncology Group studies between 1990 and 2005. This data included about half of the children in the U.S. diagnosed with leukemia in this time frame. Out of 21,600 kids and adolescents up to age 22, researchers found that 83.7% of the childhood patients diagnosed with leukemia between 1990 and 1994 were alive five years later, and 80.1% were alive ten years later. Reports of improved survival rates for children from the UK and the Netherlands show similar gains in the fight against ALL, but we are still in need of a cure. The sad fact remains that 10% to 15% of children diagnosed each year with ALL will not survive, and more research needs to be completed to make this percentage nonexistent (Figure 2).

Figure 2. 21,600 patients diagnosed with ALL from 1990-1994

5 years after diagnosis10 years after diagnosis


Further gains in research for new and innovative treatments for acute lymphoblastic leukemia have been exhibited as well. A recent report on Daily Rx, dated March 12, 2012, highlighted the new therapies under development at Case Western Reserve University School of Medicine, as published online, March 6, 2012 in ACS Chemical Biology . These therapies involve using personalized treatments and “Theranostic” agents when treating children with ALL. Researchers have discovered a link in 90% of children with ALL-unnaturally high levels of terminal deoxynucleotidyl transferase, also known as TdT. Working on an agent to target this enzyme is at the core of this research, along with continued evaluation of the activities of anti-leukemia molecules in patients. Information gleaned from research shows certain leukemia cells express molecules called CD19 on their surface. This knowledge has led scientists to explore collecting T-cells from the blood of patients, and engineering these cells to express a molecule called CAR, or chimeric antigen receptor. As the CAR molecule easily binds to the CD19 molecule, the CAR T cells can then be infused back into patients. The supposition is that this infusion, which targets the CD19 cancer cells, will create a formidable attack on these cells, thus causing their destruction. These novel and inspiring therapies are being pursued by researchers, who hope to acquire funding for additional research and future clinical trials.

Theranostics can be defined as diagnostics which are closely tied to a specific drug treatment. The FDA will require their use if a specific drug is to be prescribed. An example of this drug diagnostic junction, or theranostic, is the Her-2 neu testing followed with treatment, if appropriate, of Herceptin, or trastuzumab. Another example of a theranostic approach is a C-kit protein test for patients, with a follow up course of treatment with Gleevac, or imatinib, for treating chronic mylogenous leukemia or gastrointestinal stromal tumors.  LGM Pharma supplies APIs to University and research companies who develop new therapies and drugs to help treat these children.  The exploration of personalized medical care through the use of Theranostics is poised to become the next wave of pharmaceutical revelations and customized care.

Products currently covered by valid US Patents are offered for R&D use in accordance with 35 USC 271(e)+A13(1). Any patent infringement and resulting liability is solely at buyer risk.

Ondansetron Offers Relief to Adult and Pediatric Patients

nauseaOndansetronis also known by the brand name Zofran. As a medication used to prevent nausea and vomiting, geared especially for patients post chemotherapy, radiation or surgery, ondansetron is a 5-HT3 receptor antagonist. By blocking the activity of serotonin, a natural substance believed to cause nausea and vomiting, ondansetron is an effective antiemetic. Offered as a tablet, a rapidly disintegrating tablet, or an oral solution, ondansetron is typically taken prior to chemotherapy and radiation treatments, as well as before major surgery, to ward off potential nausea and vomiting. Generally well tolerated, side effects of ondansetron include headache, dizziness, constipation, and diarrhea.

OndansetronZofran is marketed by GlaxoSmithKline, and there are several generic forms of ondansetron available from Teva Pharmaceuticals, Kali Laboratories and Baxter Healthcare. Dosages range from 4 to 8 milligram tablets, with the disintegrating tablets being a 4 milligram strength. The oral solution of ondansetron is 5 milligrams per 5 milliliters, or one teaspoon.

Patients experiencing post treatment or post surgery nausea and vomiting are not the only patients who can benefit from being treated with ondansetron. Routinely given to children with severe cases of gastroenteritis as an off label treatment, doctors find ondansetron to be a safer and better choice for children with the stomach flu. Phenergan, a typical drug choice for pediatricians treating children with dangerous episodes of vomiting, received an FDA warning several years ago declaring it unsafe for children under age two. In addition, older children experience overwhelming drowsiness, making it difficult for them to stay awake to eat and drink to combat dehydration, even without the ongoing nausea and vomiting. Ondansetron is efficacious as a small, one time dose, which alleviates symptoms leading to dehydration, which is especially risky for children with medical conditions such as diabetes.

Ondansetron is proving itself to be a formidable treatment for patients with Rheumatoid Arthritis who are taking methotrexate. In the January 2012 issue of Rheumatology News, a revered physician from Manchester England shared his suggestion for patients taking methotrexate, and dealing with the adverse effects of nausea. He suggested taking ondansetron 2 hours prior to a methotrexate injection, and then again 12 hours after the methotrexate dose. Dr. Richard Warren assured colleagues that taking a reliable drug like ondansetron would effectively create a better environment for patients taking antifolates, like methotrexate, which are known to cause debilitating nausea. Opportunities utilizing ondansetron are vast, with researchers exploring the use of ondansetron in patients with not only nausea and vomiting, but also as an adjunct drug in the treatment of Schizophrenia.

LGM Pharma works in close collaboration with manufacturers worldwide, and is a preferred supplier of the API Ondansetron CAS# 99614-02-5 for research and development programs.

Products currently covered by valid US Patents are offered for R&D use in accordance with 35 USC 271(e)+A13(1). Any patent infringement and resulting liability is solely at buyer risk.

Is Voriconazole the New Primary Treatment for Orbital Aspergillosis?

VoriconazoleVoriconazole is also known as the brand name Vfend, which is marketed by Pfizer. As an antifungal medication, voriconazole is typically reserved for treating patients with serious fungal infections, like invasive aspergillosis. Voriconazole is a formidable opponent for fungal infections that begin in the lungs and spread through the bloodstream to other organs, like invasive aspergillosis, as well as esophageal candidiasis. Voriconazole slows the growth of dangerous fungi, and is an antifungal medication in the class deemed triazoles. Available in both a tablet and a suspension form, voriconazole is most effective when taken every 12 hours on an empty stomach. The majority of patients will be administered voriconazole for at least fourteen days, however, the patients with invasive aspergillosis may need this potent antifungal for several months or longer. Adverse effects include vision difficulties, such as light sensitivity or blurry vision, headache, diarrhea, vomiting, dizziness and abdominal pain. Thirty percent of clinical trial participants reported visual disturbances, which is a unique adverse effect for this particular class of drugs. Vfend dosages are dispensed in 50 and 200 milligram tablets. The oral suspension of Vfend, or voriconazole, is 40 milligrams/milliliters. Vials of 200 milligrams are also available for I.V. infusions.

The online publication, Case Reports in Opthalmology, dated February 4, 2012, touted voriconazole as being a new standard treatment for Orbital Aspergillosis. This case report and clinical study was conducted by the University of Florida’s Neuro-Opthalmology Department, under the guidance of Dr. Derek Ohlstein. When treating patients suffering from the often fatal Orbital Aspergillosis, voriconazole was compared with the current standard drug of choice, Amphotericin B. Clinical research revealed a better survival rate for patients given voriconazole in lieu of amphotericin B, and patients who received voriconazole also showed a better tolerability to it, and displayed less adverse systemic effects. While amphotericin B has remained a preferred treatment for Orbital Aspergillosis for many years, researchers are questioning it’s efficacy as the gold standard of treatment for this often misdiagnosed condition. Once the patient with the infection manifests it as an orbital apex syndrome the mortality rate is 70-80%, even with the treatment of amphotericin B. Patients who have been treated with amphotericin B reported numerous side effects as well, including irreversible nephrotoxicity. As a second generation triazole antifungal, voriconazole has shown a 22% survival benefit over amphotericin B in comparative studies. Evidence is mounting in favor of utilizing voriconazole as a primary treatment for Orbital Aspergillosis, however, additional research needs to be completed.

LGM Pharma works in close collaboration with manufacturers worldwide, and is a preferred supplier of Voriconazole CAS# 137234-62-9 as well as Amphotericin B CAS# 1397-89-3 for research and development purposes. Clients can be assured of quality API products and continuous support throughout the R&D process.

Products currently covered by valid US Patents are offered for R&D use in accordance with 35 USC 271(e) +A13(1). Any patent infringement and resulting liability is solely at buyer risk.

Gefitinib Continues to be a Viable Treatment Option for Patients with Non Small Cell Lung Cancer

GefitinibGefitinib, CAS number 184475-35-2, is also known as the brand Iressa, which is marketed by AstraZeneca and Teva. Gefitinib is approved by the FDA to treat malignant and/or advanced non small cell lung cancer. Iressa has been shown to be effective in about 10% of clinical trial patients. LGM Pharma supplies gefitinib for R&D purposes, and offers assistance to clients through all stages of research.

Acting as more of an anti-tumor medication, gefitinib is not a cytotoxic, or tumor cell killing drug. Gefitinib’s effectiveness is revealed in it’s ability to interfere with and inhibit cancer cell growth. Gefitinib is able to attach to epidermal growth factor receptors (EGFRs), thus blocking the attachment of EGF, and the activation of tyrosine kinase. This subsequently keeps cancer cells from not only growing, but also multiplying. This is ideal for patients who have not shown a positive response to traditional cancer treatments, such as chemotherapy. Gefitinib can be used in these patients as a stand alone drug, or as monotherapy.
A video from The Doctor’s Channel offers reassurance to patients with advanced non-small-cell lung cancer, whose tumors harbor EGFR mutations, that gefitinib is efficacious as a first line treatment. This video is based on the study from Dr. Geoffrey Y. Ku and his colleagues at Johns Hopkins Singapore International Medical Center, which was reported in Lung Cancer, online, May 11, 2011. This insightful study included 1860 patients who were randomized to receive gefitinib or chemotherapy. The study participants all had known or clinically suspected EGFR mutations. A positive result gleaned from this study was that progression free-survival was better with the patients who received gefitinib than for those who received chemotherapy.

Side effects of gefitinib, or Iressa, are few. The only serious side effect documented has been lung damage. This occurred in just 1% of patients, in the form of interstitial lung disease. The typical dose of gefitinib is 250 milligrams, taken once daily. Caution should be taken in prescribing this drug to patients who take blood thinners, such as warfarin, as gefitinib can increase the effects of these drugs. In addition, those patients taking phenytoin (Dilantin) or rifampin may need to receive a higher dose of gefitinib, as these drugs reduce it’s efficacy. As of January 2013 the patent for Iressa from AstraZeneca will expire. Gefitinib is, and will continue be available for both treatment and research and development.

Products currently covered by valid US Patents are offered for R&D use in accordance with 35 USC 271(e)+A13(1). Any patent infringement and resulting liability is solely at buyer risk.

Dorzolamide Hydrochloride Successfully Treats Open Angle Glaucoma

Dorzolamide HCLDorzolamide Hydrochloride is an eye drop indicated for the treatment of ocular hypertension and open angle glaucoma. Also known by the trade names Trusopt and Cosopt, Dorzolamide Hydrochloride works by inhibiting the isoenzyme carbonic anhydrase, also termed CA-II. This inhibition helps to decrease the amount of fluid made within the eye, thus decreasing pressure in the affected eye(s). Those patients who have severe kidney disease, or an allergy to sulfonamide should not take Dorzolamide Hydrochloride. Typical side effects include a bitter taste in the mouth, burning and stinging in the eye after administration, blurred vision and eye dryness. Approved by the FDA in 1994, Merck currently markets Trusopt and Cosopt.

Clinical studies tout the success of dorzolamide Hydrochloride not only for humans, but also for pets. One such study, titled “The effect of dorzolamide 2% on circadian intraocular pressure in cats with primary congenital glaucoma.”, was published in the September 16, 2011 issue of Veterinary Ophthalmology. This small, but important study involved adult cats who were given a placebo daily for five days, every eight hours, and then dorzolamide 2%, for five consecutive days, every eight hours. Fluctuations in circadian intraocular pressure, or IOP, were measured as a baseline, and then throughout the study.

eyeResults were encouraging, showing topical dorzolamide 2% was effective at lowering the IOP in the glaucomatous cats. In addition, there were no adverse affects noted in the cats who participated, including no evidence of irritation to the treated eye areas as well. This galvanizing information is inspiring for future researchers looking for treatments for the ever growing pet population worldwide. Dogs are also excellent candidates for treatment with dorzolamide Hydrochloride  for open angle glaucoma. Breeds especially prone to this disease are the American Cocker Spaniel, the Basset Hound and the Boston Terrier. Patients, human and animal alike, are continuing to benefit from treatment with dorzolamide Hydrochloride.

Dorzolamide Hydrochloride CAS# 130693-82-2 is available for research and development purposes. LGM Pharma also supplies the Dorzolamide Hydrochloride (TEVA API) for compounding purposes in the U.S.

Products currently covered by valid US Patents are offered for R&D use in accordance with 35 USC 271(e)+A13(1). Any patent infringement and resulting liability is solely at buyer risk.