The details will be presented at the upcoming ASCO annual meeting two weeks from now,  but there’s a preliminary highlight released that ginger root capsules can produce a very significant reduction in chemotherapy-induced nausea.  This work validates the general recommendation to take ginger ale for an upset stomach, etc., but it’s important to note that many food and drink products use ginger flavoring rather than actual ginger.

   This study included over 600 patients, two thirds with breast cancer, who received chemotherapy along with either a placebo or one of four dose levels of ginger root starting before the chemo.  Apparently, it was important that patients began taking the concentrated ginger capsules before chemo and not at or after the time of chemo, an earlier study of ginger had found.  In the study being presented, all of the doses produced a significant improvement in nausea, particularly the middle and lower dose levels.

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My recent post about selecting the right treatment for an individual tumor is part of a long history of trying to tailor cancer therapy. Many companies offer such services, and in fact advertise them heavily. However, the oncology community as a whole has not enthusiastically embraced such approaches, as many patients suggesting these tests may have found when they raise the question. This is based on decades of general disappointment, on marketing of ideas ahead of the clinical research to really prove the value of lab-based selection of optimal treatment. Because of these issues, there are no management guidelines that include recommendations for these types of tests, certainly not in lung cancer management.

In fact, there are good reasons to be suspicious that a treatment that looks promising in a test tube model of cancer is actually going to work in real live people. This is exactly the cautionary point I raised in a prior post about the difference between pre-clinical and actual patient-based testing of cancer treatments. Many, many more cancer treatments have looked sensational in test tube and animal models than in the clinic, which should be expected because the human experience depends on absorption of the drug, and delivery through the bloodstream, while cancer cells are constantly mutating, developing resistance to our treatments all too quickly. The lab models can’t quite capture the dynamic and more challenging nature of actual living cancer in human patients. Consequently, a lab report saying drug X will work for Mr. Smith’s lung cancer often falls short on that promise. If the companies that made broad claims actually backed up their contentions with clinical data, the way investigators are trying to follow up on the MADeIT trial with a larger direct comparison of tailored vs. standard unselected chemotherapy, the oncology community would likely be much more eager to adopt such testing as a standard of care. Read the rest of this entry »

Historically, chemotherapy has had a relatively minor role in the management of brain metastases. Although there is a rather low response rate in the brain from some standard lung cancer chemo regimens, we generally conclude that most of our chemo can’t be too effective in the brain because of the blood-brain barrier (BBB) that is relatively impermeable to the majority of our commonly used chemo agents (there is some debate about whether the metastases disrupt that barrier and can allow other chemo agents to get into the brain, but that’s still a murky issue). However, some of the drugs that are routinely used to treat primary brain tumors (cancers that start in the brain tissue) can get through the BBB and reach significant concentrations that can effectively fight cancer. One of the agents that has been shown to be valuable in treating primary brain tumors is temozolomide, or Temodar, an oral chemotherapy drug that is given with radiation to the brain and also on its own off of radiation. Because it’s been shown to improve survival for patients with tumors that start in the brain, and is also helpful for patients with metastatic melanomas, it’s also been an agent that has been the focus of research questioning whether it can improve results when added to radiation, or potentially on its own, in patients with brain metastases from solid tumors like lung cancer. Read the rest of this entry »

Paclitaxel, marketed name Taxol, is among the most commonly used drugs in oncology in general, and definitely also for lung cancer, particularly NSCLC. The combination of carboplatin/taxol is the most frequently prescribed combination for advanced NSCLC in the US and is also employed in many other settings for NSCLC as well. However, there are several potential problems with taxol. It is extremely hard to dissolve and requires a solvent called cremaphor (polyethoxylated castor oil — don’t worry, it’s not on the test!) and special tubing, as well as a three hour infusion time, to administer in its most common schedule. Patients need to take multiple premedications that include steroids, which is a nuisance for lots of patients and a significant problem for some, such as those who have diabetes, because steroids can markedly increase the blood sugar levels of patients. And despite premedications, it’s not uncommon for patients to develop significant hypersensitivity reactions that can be quite serious and, rarely, fatal.

There are several novel formulations of paclitaxel and other chemotherapeutic agents that allow the same paclitaxel molecule to be delivered without the alcohol-based solvent, thereby eliminating the need for steroid premedications and a long “chair time” of patients having to spend most of their day getting chemo because it’s unsafe to give the chemo faster than that. One of these is nanoparticle (tiny little particles) albumin bound (or nab) paclitaxel, which has the scientific name ABI-007 but is commonly known as Abraxane. Not only is this special form of taxol faster to administer and doesn’t require the premedications that solvent-bound taxol does, there is also the possibility that this albumin-bound form may be delivered and picked up by the tumor than standard taxol. In fact, there is some evidence that Abraxane may be superior in some ways to standard paclitaxel in breast cancer, where it has been studied much more than it has been studied in lung cancer thus far. In a large trial with 460 predominantly (86%) chemotherapy pretreated women with breast cancer (abstract here), those who received Abraxane had a significantly higher response rate from Abraxane given every three weeks than standard taxol (21.5% vs. 11.1%), and they also had a significantly longer progression-free survival, but the overall survival was not significantly different. It also had a no hypersensitivity reactions from the Cremaphor solvent, and lower neutropenia rates and severity of neuropathy (although the neuropathy with Abraxane remains a significant side effect challenge). On the basis of this work, Abraxane was approved by the FDA in January, 2005 for recurrent or metastatic advanced breast cancer. Read the rest of this entry »

In the Keynote Lecture at the Targeted Therapies in the Treatment of Lung Cancer Conference, Dr. Joseph Nevins from Duke’s described emerging approaches for how to personalize cancer management, including who to treat, and how to treat. I described in my last posts his efforts to refine our understanding of which patients with early stage, resected lung cancer are at higher or lower risk for cancer recurrence, and therefore better or less well served by receiving adjuvant chemotherapy. His lab is also studying how gene profiles of cancers can help us refine how to treat.

Herceptin, also known as trastuzumab, is a monoclonal antibody against HER-2/neu, a protein over-expressed in a subset of breast cancers. If given to an unselected population of breast cancer population, it would have a response rate of less than 10% and would potentially not have been recognized as a valuable and active drug in treating breast cancer. On the other hand, when given to an appropriately selected population of patients with over-expression of HER-2/neu, it has a response rate of 35-50% and emerges as a remarkably useful drug for breast cancer.

Thus far in lung cancer, we have rarely individualized our treatment recommendations, and even our targeted therapies have been given in an “untargeted” way. We have just started to identify patients, using EGFR mutations and/or clinical variables like smoking status or tumor subtype, to identify some patients as better or worse candidates for tarceva or avastin. But these are very rudimentary first steps. Dr. Nevins and his colleagues at Duke are looking at an array of genes to identify classes of different tumors with certain patterns of genes turned on and off (abstract here):

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