A Glimmer of Hope Against a Vicious Adversary

Here's a bit of encouraging news for patients afflicted with the brain tumor known as glioblastoma multiforme (GBM):

U.S. biotechnology company Genentech, Inc. said on Sunday its blockbuster cancer drug, Avastin, showed encouraging results for patients with the most aggressive form of brain cancer.

A pilot study from Duke University Medical Center, published in the Journal of Clincial Oncology, showed that the combination of irinotecan, a chemotherapy drug, plus the monoclonal antibody bevacizumab produced a significant improvement in the response rate and 6 month survival of patients with progressive GBM compared with historical controls. All study patients had previously received brain radiation therapy with concurrent oral temozolomide chemotherapy.

At the risk of inducing torpitude, let me quickly summarize why this study is important:

1. Glioblastoma multiforme, the most frequent primary brain malignancy in adults, is a heinous tumor that snuffs out life not just with speed but with cruelty:

No significant advancements in the treatment of glioblastoma have occurred in the past 25 years. Although current therapies remain palliative, they have been shown to prolong quality survival. Without therapy, patients with GBMs uniformly die within 3 months. Patients treated with optimal therapy, including surgical resection, radiation therapy, and chemotherapy, have a median survival of approximately 12 months, with fewer than 25% of patients surviving up to 2 years and fewer than 10% of patients surviving up to 5 years.

For example, a major study from Europe showed that patients who receive surgery, radiation therapy and temozolomide chemotherapy have a median survival of 14.6 months and a two-year survival rate of 26.5 percent. This compares to a median survival of 12 months and a two-year survival of 10.4 percent with radiation therapy alone.

Anyone still awake? All right, then let's see the next slide:

2. Patients with progression of their GBM after treatment have less than a 20% chance of responding to second-line chemotherapy. Their lives are now measured in "6 month progression-free survival" curves, which reveal less than 15 to 20% of patients with recurrent GBM will be alive and without noticeable growth of their cancer six months after starting the clock.

By the way, expert readers of the tea leaves might notice that one can "improve" the outcomes data by including patients with a slightly less aggressive form of glioma (anaplastic astrocytoma) in second-line chemotherapy studies. This makes the treatment appear more efficacious than if one includes only patients with GBM, and is exactly the case in the review linked in the above paragraph.

So why is the Duke study of interest? Final slide, please:

3. After giving 35 patients with recurrent GBM the combination of irinotecan (chemotherapy) and bevacizumab (Avastin®, the monoclonal antibody that inhibits VEGF and thereby blocks tumor angiogenesis), the response rate was 57% and the 6 month progression-free survial was 46%, double what has been previously published. In addition, 37% of the patients were still alive one year later.

(I'm sorry I lied, but there is one more slide):

4. CONCLUSIONS:

No true advances in the treatment of solid tumors will occur without first decoding, then exploiting the myriad ways cancer cells proliferate, receive nutrients, invade and avoid the automated suicide instructions placed within each nucleus, i.e. apoptosis.

Chemotherapy combined with targeted therapy will undoubtedly prove to be a deadly combination to many types of cancers. The hard work in figuring out the why, which and how is the motivation of scientists and the stuff of dreams of junior high school kids everywhere. Let the contest between humans and their traitorous cells proceed.