Importance of nutrition in chemotherapy:

Doyle 2006: Cancer J ournal Clinics:

-Even before treatment begins, cancer can cause profound metabolic and physiological
alterations that can affect the nutritional needs for protein, carbohydrate, fat, vitamin,
and minerals.

-Symptoms such as anorexia, early satiety, changes in taste and smell, and
disturbances of the gastrointestinal tract are common side effects of cancer treatment
and can lead to inadequate nutrient intake and subsequent malnutrition.

-Substantial weight loss and poor nutritional status have been documented in more than
50% of patients at the time of diagnosis, although the prevalence of malnutrition and
weight loss varies widely across cancer types. Maintaining energy balance or
preventing weight loss is therefore vital for survivors at risk for unintentional weight loss,
such as those who are already malnourished or those who receive directed treatment to
the gastrointestinal tract.

-Other patients begin the cancer treatment process in a state of overweight or obesity,
and for some, weight gain can be a complication of treatment. Nutritional screening and
assessment for survivors should begin while treatment is being planned and should
focus on both the current nutritional status and anticipated symptoms related to
treatment that could affect nutritional status.

-Chemotherapy adversely affects how the body digests, absorbs, and uses food.
Commonly experienced symptoms of cancer and side effects of treatment that may
impact nutritional status include changes in taste or smell, loss of appetite, nausea,
vomiting, changes in bowel habits, weight change, loss of lean mass, pain, and fatigue.
If these occur, usual food choices and eating patterns may need to be temporarily
adjusted to optimize intake and meet nutritional needs.

-During active cancer treatment, the overall goals of nutritional care for survivors should
be to prevent or reverse nutrient deficiencies, to preserve lean body mass, to minimize
nutrition related side effects (such as decreased appetite, nausea, taste changes, or
bowel changes), and to maximize quality of life. Recent studies confirm the benefit of
dietary counseling during cancer treatment for improving outcomes, such as fewer
treatment-related symptoms, improved quality of life, and better dietary intake.
Providing short-term individualized nutritional support can improve appetite and dietary
intake and decrease the toxicities associated with cancer treatments.

-The use of dietary supplements such as vitamins, minerals, and herbal preparations
during cancer treatment remains controversial. For example, it may be
counterproductive for survivors to take folate supplements or to eat fortified food
products that contain high levels of folate when receiving methotrexate, that acts by
interfering with folate metabolism.

-Many dietary supplements contain levels of antioxidants (such as vitamins C and E)
that exceed the amount recommended in the Dietary Reference Intakes for optimal
health. At the present time, most cancer experts advise against taking higher doses of
supplements with antioxidant activity during treatment because antioxidants could
prevent the cellular oxidative damage to cancer cells that is required for treatments such
as radiotherapy and chemotherapy to be effective.

-In contrast, others have noted that the possible harm from antioxidants is only
hypothetical and that there may be a net benefit to help protect normal cells from the
collateral damage associated with these therapies. Whether antioxidants or any other
dietary supplements specifically are beneficial or harmful is a critical question without a
clear scientific answer at this time.

-Given this uncertainty, until more evidence is available that suggests more benefit than
harm, it is prudent for cancer survivors receiving chemotherapy or radiation therapy to
avoid exceeding more than 100% of the daily value for antioxidant-type vitamins such
as vitamins C and E during the treatment phase.

New chemo agents that show promise in H/N cancer:
Haddad 2008: NEJ M:
Several chimeric and humanized IgG antibodies that target various EGFR epitopes
have been synthesized and shown to prevent EGFR signaling by distinct mechanisms;
such antibodies have also been shown to have antitumor activity.

- EGFR tyrosine kinase inhibitors, such as gefitinib and erlotinib, bind within the kinase
domain to inhibit kinase activity, thus modulating transcription, cell-cycle progression,
cell survival, and motility, all of which facilitate invasiveness and metastasis.

Ito 2009: Molecular Pharmacology:
-Cetrimonium bromide, an existing antimicrobial was identified to have anticancer
efficacy against several human HNC cell lines with minimal toxicity toward normal cells.

-CTAB significantly compromises mitochondrial bioenergetic function, inducing cell
death primarily through the intrinsic caspase-dependent apoptotic pathway;
nonapoptotic death such as senescence and mitotic catastrophe were not observed.

-When combined with local RT, CTAB delayed tumor growth while maintaining a
favorable toxicity profile. CTAB is a known component of cetrimide, which has been
routinely used during hydatid cyst, and colorectal surgeries at concentrations
that are clinically well tolerated.

-Dysregulation of mitochondrial functions and aberrant metabolic bioenergetics are
mechanisms cancer cells have developed to resist mitochondrial-mediated apoptosis,
thereby surviving in the toxic tumor microenvironment. These features, however, can be
exploited for the development of novel anticancer therapies targeting mitochondrial
proteins and membranes to promote cell death.

-Once CTAB is concentrated into the tumor mitochondria, the H+gradient across the
inner mitochondrial membrane may begin to dissipate. Opening of the permeability
transition pore causes mitochondrial outer membrane permeabilization, a pivotal event
in the intrinsic apoptotic pathway, leading to the disruption of essential mitochondrial
functions, along with release of apoptogenic factors, such as cytochrome c

Current Data on Intra-arterial chemo for H/N cancer; what are the risks and
benefits?
Robbins, Cancer 2010:
-The most prominent concern relates to the technique used to deliver the IA infusions.
The contemporary method for IA infusions employs the transfemoral approach for the
placement of microcatheters through which the chemotherapy agent can be rapidly and
selectively infused to the tumor bed.

-which artery or arteries to infuse and whether to target the external carotid artery and
its branches on the ipsilateral side versus additional infusions through the contralateral
carotid artery system is a judgment typically made by the interventional radiologist
based on observed blood flow and anatomical location of the primary disease.

-Most often, the primary tumor can be effectively treated simply by using the carotid
artery system on the side ipsilateral to the side of the tumor, even when the lesion has
crossed the midline. Most tumors extending across the midline will continue to receive
arterial flow through the ipsilateral vessels. The decision to perform an additional
infusion through the contralateral carotid artery is reserved only for a small number of
patients whose primary disease substantially encompasses the opposite side of the
upper aerodigestive tract or who have angiographic evidence of a bilateral arterial
supply.

-Furthermore, the proportion of the infusate delivered through the contralateral arterial
system is virtually always smaller. However, in the current study Rasch et al chose to
employ bilateral infusions in the majority of patients (58 %) receiving IA chemotherapy
using the criteria of more than 1 cm extension across the midline and delivering 50%
if the infusate through the opposite vessels. Inherent to the technique of bilateral IA
infusions is the necessity to divide the total dose and, hence, diminish the effect of the
drug delivered.

- In the case of cisplatin infusion with sodium thiosulfate neutralization, an infusate that
has been divided may represent an amount that is disproportionate to the targeted
tumor volume. As a consequence, not only is the cisplatin more likely to be neutralized
by the sodium thiosulfate, but also a suboptimal dose is delivered to the tumor being
supplied by the dominant artery. The corollary is that the majority of the cisplatin
delivered through the contralateral carotid system will not pass through the tumor bed
and will be rapidly neutralized by the sodium thiosulfate circulating systemically.

-A second confounding factor to be considered when interpreting the results of the
current trial is the potential influence of human papilloma virus (HPV). It is now
recognized that HPV infects tumor cells in a large portion of patients with head and neck
cancer, including the majority of those with oropharyngeal lesions.It is also well
documented that the presence of HPV confers a better prognosis.The expected higher
survival rates for HPV positive patients is relevant in this current trial, because this
subset is likely to have done just as well when treated with the lower cisplatin dose
intensity of IV chemoradiation compared with the higher cisplatin dose intensity of the IA
arm.


-More recent approaches have included the addition of doublet or triplet induction
chemotherapy followed by chemoradiation, and the incorporation of biologic agents into
existing regimens. Despite these newer and potentially more intensive protocols, none
has yet proven to be more effective than concomitant single agent IV cisplatin
chemoradiation.