2006/08/28

Our Precious Girls

CANCERS of the CERVIX : Best measure is Prevention.

Human Papilloma Viruses (HPV) are a large group with 100+ subtypes that usually present as a self-limited infection. Certain HPV strains are known to be strongly associated with the genesis of cervical cancer, and similar mechanisms may apply to HPV+ cancers of the vulva, anus, and throat. Merck"s GARDASIL is a vaccine that was developed against known culprits HPV 6, 11, 16, 18. Three injections over six months are necessary for protection against infection by these subtypes which cause the majority of cervical cancer in the US. It is a pure preventive, not a targeted therapy. As such, it can't impact upon established disease. 

So then, given the predominantly sexual mode of HPV transmission, the question now arises– how young should girls be at vaccination to allow for maximum benefit from this new intervention? The US trials have looked at girls as young as 9 years of age. As a doctor, starting them in the pre-sexual years makes great sense to me. As a parent in a conservative society, it gives me pause: Will our girls read an implicit message there?

Social norms, religious objections, parental desires aren't nearly as straightforward as science. There lies the rub.

photo by timcunnup (photobucket)


2006/08/24

Colorectal Cancer WebClips

There is no way that an oncologist can survive without the internet these days, not with the furious rate of developments in the field. Patients who mine the Web for info are best served by peer-reviewed sites (see links) for their own safety. Journal articles, commentaries, summaries etc need method & data evaluation, coupled with some insight into basic & clinical science. Discuss them with your physician.

COLORECTAL CANCER
  • Screening: Radiographic "virtual" colonoscopy (actually, colonography) is not quite ready to replace optical colonoscopy for colorectal cancer screening. The most common complaint is that you can't biopsy suspicious lesions with the new procedure. Hmm… the GI guys are especially wary, while the x-ray people seem to be ardent fans. A cost comparison for the Philippines should be interesting. In any case, virtual colonography will have to do if the patient absolutely refuses standard endoscopy, is medically unfit for sedation etc, has a partial colon obstruction that a scope can't squeeze through… *Rex DK, Lieberman D. ACG Colorectal cancer prevention action plan: Update on CT-colonography. American Journal of Gastroenterology. 2006;101:1410-1413.

  • Resectable Disease: A study in this month's JCO reports that physical activity may be an independent factor in reducing colorectal cancer's recurrence & death rates after definitive treatment. As the accompanying editorial says, "It's time to get moving!" *Meyerhardt JA, Heseltine D, Niedzwiecki D, et al: The impact of physical activity on cancer recurrence and survival in patients with stage III colon cancer: Findings from CALGB 89803. J Clin Oncol 24:3535-3541, 2006  

  • Advanced/Stage IV: Chemotherapy-based cancer treatment leading to the disappearance of liver metastases on a CT scan/MRI/PET does not mean cure in the great majority of cases. Surgery must still be considered in this setting, where possible. *Benoist S, Brouquet A, Penna C, et al: Complete response of colorectal liver metastases after chemotherapy: Does it mean cure? Journal of Clinical Oncology 24: 3939-3945, 2006



2006/07/03

Medical Oncology’s Nibs and Mabs

Targeted therapy is changing cancer treatment. 

Its a great time to be an oncologist. Tremendous toys!  Hats off to modern science-- if we forget about costs & exclusivity for a minute, we’d be dizzily restructuring our ongoing protocols.

Normal tissues grow & die in a controlled manner. They rely upon interactive signals and factors to initiate, then complete, important functions. In fact, the way cells obediently "go jump in the lake" on command may give you nightmares about dictatorships and the natural order of things. Cancer is the disease marked by loss of that order. The signals get messed up and the factors are mis-used. The abnormal cells keep growing & refuse to die. Sounds like a rebellion, doesn’t it?

Targeted therapy is one cool way to "salvage" the rebels.  It is great stuff! When you specify a tumor target, you avoid many side effects resulting from normal tissue injury or death (such as those caused by radiation & most chemotherapy agents).  Its not an entirely new idea.  Hormonal manipulation has been around for some time for tumors which express the corresponding receptors on their cell surfaces.  What’s new is that The Human Genome Project and other humongous brain trusts have clarified new tumor-specific targets for similar manipulation.  We can now zero in on teeny molecules inside of & exterior to the cancer cell, even on its blood supply.  By doing so, we are able to hinder cancer cell function, growth, & propagation while largely avoiding damage to other tissues.

I use a mnemonic to broadly classify the manner by which these targeted agents do their thing and, consistent with my personality, its by no means 100% scientific.  Nibs (imatinib, gefitinib, erlotinib, lapatinib, sunitinib, sorafenib, etcetera) interfere with signalling pathways which control functions like cell proliferation & death.  Mabs are antibodies that attach to predetermined molecules. They can block receptors to prevent growth factors from acting on the target cell, incite direct cell lysis by the patient’s own immune response, act as guides for killer isotopes attached to them, and so on. (Trastuzumab, bevacizumab, cetuximab, ibritumomab, alemtuzumab, rituximab). Then there are the cancer vaccines, which may someday effectively build up & use patients’ defenses against their own malignancies.

Can these amazing drugs take the place of chemotherapy? In a few instances, yes- esp in those malignancies where chemo doesn’t work well anyway, like Gleevec for GIST & Sutent for renal cell cancer. In many cases, however, the 2 treatment types are complementary or even synergistic, i.e., the benefit when given together is more than the sum of one treatment’s effect. Are they curative in very advanced disease? No. They do improve on the success rates of conventional therapies in more limited stages (as in "adjuvant" herceptin in breast cancer or rituximab added to chemo in certain lymphomas).

Thank you ImClone, Amgen, Genentech et al for the gazillions you invested in R&D. We wish you the Big Payoff that you deserve, so that you can do even more research. Through such efforts, cancer control & therapy may someday be a matter of prescribing the right pill.

But… when will the Indians & Chinese do decent clones for the benefit of those who don’t receive state health subsidies?  Politics again. Ahh me.

Image from Harper’s Weekly; 5 March, 1864




      



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