[gdpawel]

Using the CellSearch technique that quantifies circulating tumor cells, German investigators have shown that neoadjuvant chemotherapy with paclitaxel (taxol) causes a massive release of cells into the circulation, while at the same time reducing the size of the tumor. The finding could help explain the fact that complete pathologic responses do not correlate well with improvements in survival.

Circulating tumor cells (CTCs) are cancer cells that have detached from solid tumors and entered the blood stream. This can begin the process of metastasis, the most life-threatening aspect of cancer. To metastasize, or spread cancer to other sites in the body, CTCs travel through the blood and can take root in another tissue or organ.

In the study, breast cancer patients undergoing neoadjuvant chemotherapy gave blood samples in which epithelial antigen-positive cells were isolated. Such cells are detected in most breast cancer patients but are rarely found in normal subjects. The investigators measured the levels of cirulating tumor cells before and during primary chemotherapy with several different cytotoxic agents.

What this recent study has shown is that in three different paclitaxel (taxol) containing regimens, as the tumor collapses (a clinical response, not cure), it produces the greatest release of circulating tumor cells. The study has not looked at any other combination regimens.

The tumor shrinks, but more cells are found in the circulation. This corresponds with a high pathologic complete response during paclitaxel treatment, but in the end, this is not reflected in improved survival. These cells are alive in the circulation. The results indicate that monitoring of circulating tumor cells can contribute to understanding of tumor-blood interactions and may provide a valuable tool for therapy monitoring in solid tumors.

The results of this kind of study are coming out slowly and quietly and indicate that taxol containing regimens didn't prolong survival over other more conventional and less expensive cytotoxic drugs. It may indeed give clincial response (tumor shrinkage), sometimes impressive, however, these are mostly short-lived and relapses after a response to taxanes (taxol) are often dramatic.

Even before the advent of the CellSearch technique, it had been observed in "cell death" cell culture assays, that there was an increase in the number of metabolic activity of mitochondria of the surviving cells from Taxol therapy, even in cases where the majority of the cells are being killed by Taxol. It may indeed give clinical response (tumor shrinkage), however, these are mostly short-lived and relapses after a response are often dramatic.

Even if one or more chemotherapy regimen is identified as being likely to work on a particular cancer, has the science advanced to tell us whether application of the chosen chemotherapy regimen will not cause other changes that also cause cancer to later return and perhaps be even harder to treat? Is it a case of chemotherapy being bad, in cases where it apparently works? Traditional chemotherapy is mutagenic (changes in form), you might kill off a whole lot of cancer, only to cause a mutation in the remaining cancer, such that the remaining cancer behaves in a more agressive fashion.

Cancers that are a product of these genetic mutations release cells from the usual controls of proliferation and survival, making them so much harder to fight it. Following this mutation, the cancer cells acquire the ability to proliferate without the normal restraints. As the cancer grows, it may infiltrate and destroy the surrounding tissue, and metastasize by penetrating into blood vessels, lymph nodes, and body cavities. Distant metastasis via the bloodstream may affect virtually any organ (the lungs, bones, liver, adrenals, and even the brain).

These studies tell us that much more work needs to be done, and oncologists need to adapt treatment to the patient. There are over 100 chemotherapeutic agents, all of which have approximately the same probability of working. The tumors of different patients have different responses to chemotherapy. It requires individualized treatment based on testing individual properties of each patient's cancer.

Source: (Oncol News Int'l, Vol 14, #5, May '05)