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Old 07-23-2015, 05:39 PM
gdpawel gdpawel is offline
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Default Chemotherapy Use, Performance Status, and Quality of Life at the End of Life

ABSTRACT

Importance Although many patients with end-stage cancer are offered chemotherapy to improve quality of life (QOL), the association between chemotherapy and QOL amid progressive metastatic disease has not been well-studied. American Society for Clinical Oncology guidelines recommend palliative chemotherapy only for solid tumor patients with good performance status.

Objective To evaluate the association between chemotherapy use and QOL near death (QOD) as a function of patientsí performance status.

Design, Setting, and Participants A multi-institutional, longitudinal cohort study of patients with end-stage cancer recruited between September 2002 and February 2008. Chemotherapy use (n = 158 [50.6%]) and Eastern Cooperative Oncology Group (ECOG) performance status were assessed at baseline (median = 3.8 months before death) and patients with progressive metastatic cancer (N = 312) following at least 1 chemotherapy regimen were followed prospectively until death at 6 outpatient oncology clinics in the United States.

Main Outcomes and Measures Patient QOD was determined using validated caregiver ratings of patientsí physical and mental distress in their final week.

Results Chemotherapy use was not associated with patient survival controlling for clinical setting and patientsí performance status. Among patients with good (ECOG score = 1) baseline performance status, chemotherapy use compared with nonuse was associated with worse QOD (odds ratio [OR], 0.35; 95% CI, 0.17-0.75; P = .01). Baseline chemotherapy use was not associated with QOD among patients with moderate (ECOG score = 2) baseline performance status (OR, 1.06; 95% CI, 0.51-2.21; P = .87) or poor (ECOG score = 3) baseline performance status (OR, 1.34; 95% CI, 0.46-3.89; P = .59).

Conclusions and Relevance Although palliative chemotherapy is used to improve QOL for patients with end-stage cancer, its use did not improve QOD for patients with moderate or poor performance status and worsened QOD for patients with good performance status. The QOD in patients with end-stage cancer is not improved, and can be harmed, by chemotherapy use near death, even in patients with good performance status.

[url]http://oncology.jamanetwork.com/article.aspx?articleid=2398177
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Old 07-23-2015, 05:40 PM
gdpawel gdpawel is offline
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Default Chemotherapy just in case?

In regards to what "theoretical" microscopic disease may be left behind, spontaneous remissions in cancer suggests that the body can heal itself. It seems like most apparently occur in just a few types of malignancies: malignant melanoma, renal cell cancer, low-grade non-Hodgkin's lymphoma, chronic lymphocytic leukaemia and neuroblastoma in children. However, spontaneous remissions do occur in vastly different other types of cancers.

The very existence of spontaneous remissions represents a threat to some in the cancer industry. But such anomalies can pave the way to a better understanding of the causes of cancer which can then lead to rational therapies. Historical observations of spontaneous remissions of breast cancer after the onset of menopause lead to approaches of hormonal treatment which is a mainstay of adjuvant and palliative therapy in breast cancer.

Regardless, spontaneous remissions represent an important clue as to how the body can defend itself against cancer. Researchers should think "outside the box" at this important phenomenon rather than see it as a threat to their conventional thinking and appreciate the insight it may provide to rational approaches to cancer treatment.

For some common cancers, it is not clear that early detection and treatment actually prolong patients' lives. Early detection may just mean patients spend a longer time knowing they have cancer, and yet die at the same time they would have died anyway if the tumor had been diagnosed later. A decision to forgo cancer screening can be a reasonable option.

And the mutagenic (changes in form) effects of the wrong chemo can start the chain of metastatic events. A chemo-induced gene mutation can happen when the original chemo received does not work. The cancer can either continue to grow or comes back. When it does this, the tumor acts more aggressively. The mutagenic effects of chemotherapy on a genetically-unstable tumor, drives the tumor into a state of more aggressive behavior. You may even 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 aggressive fashion.

When your first-line treatment does not work, there are several downsides:

It can take months for tests to confirm whether chemotherapy has been effective. If it has not, the cancer may have progressed. And then the patient, if strong enough, has to go back to square one and try again with something new.

Ineffective chemotherapy can cause the patient to become sicker or suffer serious side effects with no treatment benefit.

Many chemotherapies can cause mutations leading to drug-resistant tumors. Exposure to drugs may actually diminish subsequent benefit from treatment.

With patients absorbing a larger percentage of their own costs of care, the expenses associated with ineffective treatments become a personal financial burden.

Ineffective chemotherapy can diminish not just the quality of life but also the quantity of life through organ toxicity, immunosuppression, and/or by inducing mutations in genetically unstable tumor cells to more aggressive phenotypes.

The tumor microenvironment is characterized by regions of fluctuating hypoxia, low pH, and nutrient deprivation. Each of these microenvironment factors has been shown to cause severe disturbance in cell metabolism and physiology.

Both in vivo and in vitro data demonstrate that exposure of tumor cells to adverse conditions can directly cause mutations, contributing to genetic instability (Mutat Res;1998 May 25;400[1-2]:439-46).

Mutagenesis induced by the tumor microenvironment

[url]http://www.ncbi.nlm.nih.gov/pubmed/9685702

Genetic Instability Induced by the Tumor Microenvironment

[url]http://cancerres.aacrjournals.org/content/56/24/5754.full.pdf

Genetic instability and the tumor microenvironment

[url]http://www.ncbi.nlm.nih.gov/pubmed/15603753
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