Results tagged “Oncology” from Pathophilia

NBA legend Kareem Abdul-Jabbar, 62, has Philadelphia-chromosome-positive (Ph+) chronic myeloid leukemia (CML), according to numerous news sources. ABC News reports that Abdul-Jabbar was diagnosed with the disorder in December of last year. What treatment Jabbar has received to date is unclear; although the LA Times states that the disease is managed with "daily oral medication" (probably imatinib [Gleevec; Novartis]) and regular "blood analysis."

Here are some facts about CML and its treatment, according to the NCCN Clinical Practice Guidelines:

• CML accounts for 15% of adult leukemias. This year, an estimated 5050 cases will be diagnosed, and 470 will die of the disease.
• The median age of onset is 67 years.
• The disease is characterized by a translocation between chromosomes 9 and 22, resulting in the formation of the Philadelphia chromosome. The translocation results in a fusion gene, BCR-ABL, which is believed to play an important role in the development of CML. The fusion protein produced by BCR-ABL is an oncogene, with unregulated tyrosine-kinase (TK) activity.
• CML occurs in 3 phases: chronic, accelerated, and blast. CML is usually diagnosed in the chronic phase.
• Untreated CML will progress to advanced disease in 3-5 years.
• First-line treatment for chronic Ph+ CML is imatinib, a selective inhibitor of the TK portion of the bcr-abl fusion protein. 
• Responses to the initial treatment of CML are monitored periodically (eg, every 3 months), by assessing bone marrow cytogenetics (ie, cytogenic response [CyR]) and transcript numbers of the BCR-ABL gene (ie, molecular response).
• Long-term data (median follow-up, 60 months) for first-line imatinib: complete CyR, 87%; overall survival, 89%.
• The most common high-grade toxicities with imatinib: neutropenia and thrombocytopenia. Rare cardiotoxicity has been reported with long-term therapy.
• The most common adverse events with imatinib: GI disturbances, edema, rash, and musculoskeletal complaints.
• Management of disease progression that occurs during imatinib therapy may include increasing the imatinib dosage; the use of an alternative TK inhibitor (dasatinib [Sprycel; BMS] or nilotinib [Tasigna; Novartis]); hematopoietic stem cell transplantation (HSCT), or enrollment in a clinical trial. Traditional chemotherapy regimens may also be considered for blast crisis.

The NCCN guidelines conclude, "The development of imatinib...has revolutionized the treatment of CML." Before the advent of imatinib, CML was treated medically with interferon alpha and low-dose cytarabine. According to ABC, Abdul-Jabbar is a spokesperson for Novartis, the manufacturer of imatinib. 

The FDA approved imatinib for the first-line treatment of CML in December 2002.

NCCN = National Comprehensive Cancer Network.

Image of Abdul-Jabbar in 2007 from Flickr.

And another thing that Avastin (bevacizumab; Genentech) may be good for:

The anti-VEGF monoclonal antibody improved hearing loss and reduced tumor volume in patients with growing vestibular schwannomas. The conclusions are based on data from a small, first-of-its-kind study of patients with neurofibromatosis (NF) type 2—data which are available in an early release article from The NEJM.

Ten consecutive patients with NF type 2 and progressive vestibular schwannomas (who were not candidates for or declined the standard treatment of surgery and radiation therapy*) received at least one dose of bevacizumab (5 mg/kg every 2 weeks). The median annual growth rate of schwannomas before treatment was 62%, and the median duration of treatment was 12 months. (The rationale for assessing bevacizumab in NF-associated schwannomas is based on the expression of VEGF in tumor cells. However, the expression of the VEGF receptor, VEGFR-2, on tumor vessels is not particularly high—which suggests that an anti-VEGF-receptor drug is less likely to be of benefit than bevacizumab.)

In a retrospective analysis, 9/10 tumors shrank (best median response, 26% reduction) after bevacizumab treatment, and 6 demonstrated an imaging response. Only 1 patient experienced an increase in tumor volume (of 32%). Tumor reduction strongly correlated with baseline vasogenic edema on MR images (ie, the mean apparent diffusion coefficent). Improvements in hearing (at <12 weeks) were observed in 5 of 7 eligible patients and were progressive and durable (up to 16 months) in most.

This pilot study was not funded by Genentech; although 1 author (Gregory Sorensen, MD) reported receiving grant support from the company.

NF2 is a dominantly inherited disorder with a prevalence of 1 in 25,000. The most common tumor type associated with the condition is vestibular (or acoustic) schwannomas, benign tumors of the 8th cranial nerve. Growth of tumors causes progressive hearing loss, as does surgical and radiation therapy. Progressive vestibular schwannomas can also produce brainstem compression.

In May, the FDA approved Avastin for the treatment of the uniformly fatal brain tumor, glioblastoma multiforme, after standard therapy.

VEGF = vascular endothelial-cell growth factor.

* Eight patients were at high risk for complete hearing loss with standard therapy.

Delivering chemotherapy to brain tumors is particularly challenging because of the blood-brain barrier (BBB), the collection of tight junctions between endothelial cells in cerebral blood vessels. When intact, these protective junctions prevent the passage of a number of substances—including chemotherapeutic molecules—from the systemic circulation into the brain tumor bed. The key to effective, targeted therapy of brain tumors is to 1) selectively disrupt the BBB to allow the entry of cancer-killing drugs and then 2) reestablish the BBB so that chemotherapeutic agents are retained within the tumor bed.

Biomed engineers at Duke have constructed a prototype of an intravascular catheter, which can deliver BBB-busting hyperthermia* and provide real-time 3D imaging of brain tumors. The thin, flexible catheter is intended to be snaked through the internal jugular vein (which obviates the need for invasive cranial surgery) and manipulated into the dural venous sinuses. The investigators' proof-of-concept experiments, performed in dogs, was published in this month's issue of Ultrasonic Imaging.

The investigators concluded that their next-generation device must be smaller and more flexible than the prototype, to negotiate the curves of the cerebral vasculature. The long-term plan for the catheter is to obtain fluoroscopic-guided access to brain tumors through the venous sinuses, administer BBB-disrupting heat, which would then trigger the release of chemotherapeutic agents to the tumor bed.

* A temperature rise of approximately 5 degrees C.

Depiction of dural sinus system from Gray's Anatomy.