1. There appears to be a number of patients who have had long-term survival after high dose therapy, but there are a number of patients whose tumors are responsive to chemotherapy who have had long-term remissions from standard dose chemotherapy, as well as a number who show no difference in survival when treated with standard-dose or high-dose chemotherapy. Does chemotherapy shorten survival of some patients, while prolonging the survival of others? You do help some patients, but for every patient helped, there's another one you hurt.

It may be better not to give more aggressive and toxic, mutagenic and immunosuppressive combinations, but to give targeted single agents, or give least toxic, mutagenic synergistic combinations. You may want to reserve aggressive therapy for those patients who will derive more benefit than harm, while identifying the most promising treatment regimens for everyone. In patients with tumors very resistant to cytotoxic chemotherapy, the most promising treatments may be angiogenesis inhibitors, growth factor inhibitors, or more integrative medicine approaches.

The problem is that ineffective, aggressive chemotherapy can diminish not just the quality of life but also the quantity of life, through organ toxicity, immunosuppression, and inducing mutations in genetically unstable tumor cells to more aggressive phenotypes.

Maybe more emphasis should be put on matching treatment to the patient, through the use of individualized pre-testing, having more respect for minimal partial response or stable disease, when it can be achieved through use of the least toxic and mutagenic drug regimens, and reserve the use of higher dose therapy or aggressive combination chemotherapy to those patients with tumor biologies most amenable to attack and destroy by these aggressive treatments?

Posted at 5:48PM on Dec 23rd 2006 by Greg Pawelski

2. I'd like to see the study that says for every one helped another is hurt. I'd like to see the study that says that chemotherapy shortens the lives of some patients.

The general feeling now is that traditional chemotherapy works for estrogen receptor neg. patients, while the newer chemotherapies like tamoxifen work so well for estrogen receptor positive cancers, traditional chemotherapies are not needed.

If I was an estrogen receptor negative patient and I was told that there was a 50% chance that the chemotherapy would shorten my life, I'd like to know how the doctor knew that.

Posted at 9:09PM on Dec 23rd 2006 by hchcec

3. No one should try to guarantee any patient of any kind of chances whether they are 50% or any other number. There is never really any guarantee. It is impossible to predict accurately no matter what.

Some people deserve the chance that chemo can give them and then I have to wonder why so many are accepting of chemo when it can have such disastrous and long-lasting side effects. It's been shown in some study, that I can't remember the name of, that some children who have had to go through chemo during childhood cancer treatment will ultimately have immune system issues later in life. Well....yeah! Why not?

Not only that, right here in cancer blog, I was reading about kidney transplant patients who are at risk for developing cancer later on. Well...after taking immunosuppresive drugs....uh.....yeah!

I see a pattern developing here. Am I alone in that?

Posted at 5:05PM on Dec 27th 2006 by MaryD

4. Am J Oncology Rev 1(3):169-70, 2002 Chemotherapy in the treatment of patients with metastatic breast cancer: high-dose, low-dose, what have we accomplished? Dana-Farber Cancer Institute (Harvard Medical School), Boston.

J Clin Oncol 2002 Feb 1;20(3):743-50 High-dose versus standard chemotherapy in metastatic breast cancer: comparison of Cancer and Leukemia Group B trials with data from the Autologous Blood and Marrow Transplant Registry. University of Texas M.D. Anderson Cancer Center, Houston.

J Clin Oncol. 1997 Oct;15(10):3169-77. J Clin Oncol. 1998 Mar;16(3):1238-9. Impact of selection process on response rate and long-term survival of potential high-dose chemotherapy candidates treated with standard-dose doxorubicin-containing chemotherapy in patients with metastatic breast cancer. University of Texas M.D. Anderson Cancer Center, Houston.

N Engl J Med. 2000 Apr 13;342(15):1069-76;1119-20 N Engl J Med. 2000 Aug 10;343(6):439-40; discussion 440-1. N Engl J Med. 2000 Aug 10;343(6):439; discussion 440-1. N Engl J Med. 2000 Aug 10;343(6):440; discussion 440-1. Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. University of Pennsylvania Cancer Center, Philadelphia.

Lancet 1980 Mar 15;(8168 Pt 1):580-2 Failure of chemotherapy to prolong survival in a group of patients with metastatic breast cancer. Powles TJ, Coombes RC, Smith IE, Jones JM, Ford HT, Gazet JC.

Posted at 12:31AM on Dec 31st 2006 by Greg Pawelski

5. As in most cases, it comes down to "individualization." There are clearly situations where high dose therapy reliably produces cures in diseases such as testicular cancer, Hodgkin's disease, childhood leukemia, etc., while there are situations where low dose therapy does not. The problem has been the tendency to apply the lessons of these diseases to "all forms of cancer."

I don't think claiming that high dose therapy should be preferred is any more helpful than claiming that low dose therapy should be preferred. If one has a highly effective drug regimen, then this should be given at the optimum dose to achieve whatever it is supposed to achieve. If it has the capacity to achieve destruction of tumor cells directly, then a sufficient drug dose should be given to achieve this goal. If it does not have the capacity to destroy tumor cells, and say that a drug works through an effect like angiogenesis, then the drug should be given at a dose consistent with this aim (which is generally lower).

Take the case with ovarian cancer. Some ovarian cancer patients do have tumors which are quite sensitive to platinum. These patients should be treated with aggressive platinum dosing, because you have a good shot at getting a very long term survival. But giving high dose platinum to patients with intrinsically resistant disease causes more harm than help. Intensive chemotherapy should be selected in curable cancers such as small cell and testicular cancers, but we should select low dose chemotherapy with molecular targeting therapy such as anti-angiogenic drugs in non-curable cancers. Less toxic chemotherapy could lead to longer survival with better quality of life.

Posted at 5:25AM on Jan 21st 2007 by Greg Pawelski