1.
Nanotech News
March 20, 2006
Magnetic Nanoparticles Separate Tumor Cells from Healthy Blood Cells

...metastatic lesions, and not primary tumors, are the primary cause of cancer's lethality.

Since metastatic lesions invariably form when primary tumor cells migrate through the bloodstream, researchers have been developing methods for removing tumor cells from the bloodstream.

...tumor cells could be separated easily from healthy cells using a commercial magnetic cell sorter.

J Cancer Res Clin Oncol. 2006 May;132(5):287-92. Epub 2006 Jan 24.

Differential interaction of magnetic nanoparticles with tumor cells and peripheral blood cells.

Clement JH, Schwalbe M, Buske N, Wagner K, Schnabelrauch M, Gornert P, Kliche KO, Pachmann K, Weitschies W, Hoffken K.

Department of Internal Medicine II, Friedrich Schiller University
Jena, Erlanger Allee 101, 07740, Jena, Germany,
joachim.clement@med.uni-jena.de.

PMID: 16432758 [PubMed - in process]

http://nano.cancer.gov/news_center/nanotech_news_2006-03-20e.asp

Posted at 10:06AM on Apr 10th 2006 by Stuart Kelley

2. Drug Selection in Cancer Treatment

The American Society of Clinical Oncologists (ASCO) says oncologists should make chemotherapy treatment recommendations on the basis of published reports of clinical trials and a patient's health status and treatment preferences.

How about published reports of clinical trials?

More chemotherapy is given for breast cancer than for any other form of cancer and there have been more published reports of clinical trials for breast cancer than for any other form of cancer.

According to NCI's March 31, 2006 official cancer information website on "state of the art" chemotherapy for recurrent or metastatic breast cancer, it is unclear whether single-agent chemotherapy or combination chemotherapy is preferable for first-line treatment. At this time, no data support the superiority of any particular regimen. So, it would appear that published reports of clinical trials provide precious little in the way of guidance.

Single agents that have shown activity in metastatic breast cancer:

Anthracyclines.
Doxorubicin, Epirubicin, Liposomal doxorubicin, Mitoxantrone.
Taxanes.
Paclitaxel, Docetaxel, Albumin-bound nanoparticle paclitaxel (ABI-007 or Abraxane)
Alkylating agents.
Cyclophosphamide.
Fluoropyrimidines.
Capecitabine,5-FU.
Antimetabolites.
Methotrexate.
Vinca alkaloids.
Vinorelbine,Vinblastine,Vincristine.
Platinum.
Carboplatin,Cisplatin.
Other.
Gemcitabine, Mitomycin C.

Combination regimens that have shown activity in metastatic breast cancer:

CA: cyclophosphamide and doxorubicin.
Docetaxel and doxorubicin.
CAF: cyclophosphamide, doxorubicin, 5-fluorouracil.
CMF: cyclophosphamide, methotrexate, 5-fluorouracil.
Doxorubicin and paclitaxel.
Docetaxel and capecitabine.
Vinorelbine and epirubicin.

http://www.cancer.gov/cancertopics/pdq/treatment/breast/HealthProfessional/page8#Section_297

In the total absence of guidance from published reports of clinical trials then, what basis are treatment regimens selected instead? ASCO says that this should be further based on a patient's health status and patient treatment preferences.

So what is being done?

Just published in the journal Health Affairs is a joint Harvard/Michigan study entitled "Does reimbursement influence chemotherapy treatment for cancer patients?" The authors documented a clear association between reimbursement to the oncologists for the chemotherapy of breast, lung, and colorectal cancer and the regimens which the oncologists selected for the patients. In other words, oncologists tended to base their treatment decisions on which regimen provided the greatest financial remuneration to the oncologist.

http://content.healthaffairs.org/cgi/content/abstract/25/2/437

A March 8, 2006 New York Times article described the study. One of the more interesting aspects of the story was the following: "An executive with the American Society of Clinical Oncology, Dr. Joseph S. Bailes, disputed the study's findings, saying that cancer doctors select treatments only on the basis of clinical evidence. 'All of us are looking at clinical trials,' he said."

http://www.nytimes.com/2006/03/08/health/08docs.html?ex=1145160000&en=584b5c2aa35995a3&ei=5070

So ASCO's Dr. Bailes maintains that drugs are chosen only on the basis of "clinical evidence."

Well, Dr. Neil Love reported in a survey of breast cancer oncologists based in academic medical centers and community based, private practice medical oncologists. The former oncologists do not derive personal profit from the administration of infusion chemotherapy, the latter oncologists do derive personal profit from infusion chemotherapy, while deriving no profit from prescribing oral-dosed chemotherapy.

The results of the survey could not have been more clear-cut. For first line chemotherapy of metastatic breast cancer, 84-88% of the academic center-based oncologists (who are motivated to keep off-protocol patients out of their chemotherapy infusion rooms to reserve these rooms for on-protocol patients) prescribed an oral-dose drug (capecitabine), while only 13% prescribed infusion drugs, and none of them prescribed the expensive, highly remunerative drug docetaxel.

In contrast, among the commuity-based oncologists, only 18% prescribed the non-remunerative oral-dose drug (capecitabine), while 75% prescribed remunerative infusion drugs, and about 40% prescribed the expensive, highly remunerative drug docetaxel.

http://patternsofcare.com/2005/1/editor.htm (figure 37, volume 2, issue 1, 2005)

The existence of this profit motive in drug selection has been one of the major factors working against the individualization of cancer chemotherapy based on testing the cancer biology.

In the absence of cell culture assay testing, oncologists will continue to base their drug selections on reimbursement more than on any other single factor. Absent assay testing, they are free to choose the most remunerative therapy (infusional).

By utilizing cell culture assay tests, they do so either because they want to choose the treatment which is most likely to work or that is what their patients want. Afterall, even ASCO endorses "patient's treatment preferences." Either way, they are forced to consider information going beyond reimbursement.

There are patients who have progressive disease after first-line therapy, only to enjoy a dramatic benefit from second or even third line therapy, and these patients would have been much better served by receiving the most probable active treatment "the first time around."

Posted at 4:00AM on Apr 14th 2006 by Gregory D. Pawelski