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Nutritional Supplementation and Fatigue in a Patient with Adenoid Carcinoma
Lisa Colodny, Pharm D. BCNSP
Abstract: Fatigue is commonly experienced by a number of patients with
differing types of cancers who are undergoing various treatments including
radiotherapy. While the etiology of radiation induced fatigue is not known,
there is much speculation as to its causes and as a result, its treatment. The
case of a 43-year-old, otherwise healthy male, recently diagnosed with adenoid
carcinoma is evaluated and reviewed. After diagnosis, he underwent surgery to
remove the tumor, and received a total amount of 6000 cGy for 42 days and
initiated nutritional supplementation with Propax. His radiotherapy was well
tolerated with no significant adverse events. Based on patient surveys, his
fatigue scores significantly improved even as his radiation treatments
progressed. Patient diaries report him to be optimistic and in otherwise good
health. He has been able to return to a lifestyle similar to that before
diagnosis of his cancer. Although randomized, blinded, clinical studies are
pending, nutritional manipulation may improve the quality of life for patients
by decreasing the fatigue and malaise commonly encountered in cancer patients.
Introduction
Fatigue is a common complaint of oncology patients who undergo radiotherapy(1 -
5). Even though it commonly occurs, it is not well understood and there are
numerous theories regarding its severity and prevalence in a patients daily
routine(5). While as many as 32% of cancer patients report that fatigue
adversely affects their lives, it is recognized by only about 76% of
oncologists(5). Of more importance, both patients and physicians report fatigue
to be a more prominent adverse event than pain. This is especially interesting
given that 74% of patients believe fatigue is an untreatable adverse event that
must simply be endured(5).
The factors that affect the level of fatigue in patients with cancer have not
been formally recognized. However, Smets et al evaluated fatigue in patients
undergoing radiation and compared it with fatigue in the general population.
Both disease-free and cancer fatigue was significantly associated with
differences in gender, physical distress, pain, sleep quality, functional
disability, psychological distress and depression(6). Thirty-four percent of
cancer patients reported fatigue to be more severe than was expected and 39%
listed fatigue as one of the most problematic symptoms of the radiation
treatments(6).
As evasive as its etiology, recognized or approved treatments appear to be even
more illusive. It is not surprising then that healthcare providers continue to
struggle with a variety of quality of life issues (including fatigue). As a
result some clinicians may consider nutritional supplements to increase the
body's inherent defenses against disease, medications, and the assault of
aggressive radiation.
Objective
To evaluate the effectiveness of nutritional supplementation for decreasing
fatigue in an adenoid cystic carcinoma undergoing surgery and radiation.
Case History
A previously healthy 43 year old male was diagnosed in January 1999 with
asymptomatic adenoid cystic carcinoma. In Febuary he complained of nasal
stuffiness and a lump on the side of his nose. CT of chest, abdomen, and pelvis
were negative for metastasis. At this time aggressive excision with
reconstruction was recommended. Alternative treatments included radiotherapy and
hyperthermia.
He acknowledged an anaphylactic allergic reaction and rash to penicillin.
Medications included alprazolam and Ambien at bedtime as needed. He denied any
significant past medical history. However, past surgical history included PRK to
both eyes approximately 1 year ago, bilateral inguinal hernia repair at 10 years
of age, and correction of undescended testicle at 12 years of age. It is not
known if the undescended testicle resulted from the hernial surgery. He denied
tobacco use and reports occasional alcohol consumption. Family history
significant for controlled Chronic Lymphocytic Leukemia for his 70 year-old
father.
Initial physical examination acknowledged a well developed, well nourished and
vigorous appearing male in no acute distress. The patient reported his energy
level was appropriate and experienced no headache or migraines. He had no
complaints of blurred vision, photophobia, or diplopia. However, he did report
visual changes when looking upward to the extreme. He had no hearing changes,
shortness of breath, chest pain, or changes in appetite or bowel habits. There
was no report of neuromuscular pain or weakness.
His skin texture and color were normal without rash, cyanosis, or petechiae.
External examination reported a atraumatic, normocephalic patient without
deformity. There was no lesions or blood noted in the oral cavity. Additionally,
no jugularvenous distension of the neck was noted. Evaluation of lymph nodes
reported no submandibular, cervical, or supraclavicular adenopathy. Review of
cardiac, respiratory, and neurologic systems were insignificant.
A CT and MRI of the head and neck performed in January 1999 confirmed a 3 - 4 cm
mass that filled most of the right nasal cavity with extension through to the
subcutaneous skin of the face. Although the orbit itself appeared normal,
initial invasion of the orbital bony floor was suspected. In addition, there was
extension into the maxillary sinus. He was diagnosed with adenoid cystic
carcinoma (Stage T4N0M0) of the right maxillary sinus.
In February, patient underwent facial degloving and surgical excision of the
tumor. During the surgery, a gingivobuccal incision from the left to right
premolars and down to the maxillary bone was performed. A Dingman elevator was
used to elevate the periosteum and soft tissue on the left and right sides of
the anterior face of the maxilla carefully preserving the infraorbital nerve.
The margin of the piriform aperture was identified and incisions were made to
enter the nasal floor and midline across the nasal spine. Since CT had revealed
tumor invasion into the nasal bone and frontal processes of the maxilla,
visualization of the septum was obtained. However, examination of the
mucoperichondrium and cartilaginous septum confirmed the absence of tumor
invasion into the septum. At this time, osteotomies, similar to those performed
during medical rhinoplasty, were performed. The tumor was then removed without
difficulty and hemostasis was controlled through bipolar cautery. Multiple
sections were obtained for biopsy. Microscopic description reported lamellar
bone infiltrated by adenoid cystic carcinoma with prominent desmoplastic
reaction. The neoplasm was composed mostly of monotonous round blue cells that
revealed ovoid nuclei with vesicular chromatin. The cytoplasm was present with
closely packed cells arranged in large solid sheets and nests. There was
scattered tumor nests with several small lumina formations, some with central
necrosis. Scattered mitotic figures were also present.
Laboratory values (potassium, sodium, chloride, CO2, BUN, serum creatinine,
albumin, total bilirubin, alk phos, and AST) were normal. However, glucose
levels were elevated on 2 consecutive days while protein and calcium were
decreased. Complete blood count summaries can be found in figure 1. Only
hemoglobin and hematocrit reductions appeared slightly abnormal.
The septal bone was harvasted for reconstruction surgery post evaluation of
tissue biopsies. The final analysis of the frozen sections was negative for
tumor. After surgery he was transferred to the medicine floor with a nasal
splint. He did very well post operatively. By day 2 he was tolerating a soft
diet. He had minimal edema on day 3 and was able to tolerate oral foods well. He
remained afebrile and was discharged home on hydrocodone for pain and
clindamycin empircally for infection. Once he was at home, he began nasal
treatment with steam and irrigation.
He tolerated his first radiation treatment in March (11th) without any
difficulty and received his last treatment in on April 21(Total dose of 6000 cGY
for 42 days). During radiation, he complained of early morning nausea that was
relieved with sleep and treated with lorazepam 1mg 3 times daily, headache that
was treated with hydrocodone, and dry eyes relieved with refresh P.M. drops. He
also had some opthalmic discharge that was treated with gentamicin opthalmic
ointment. A well tolerated diet included cottage cheese, ice cream, saltine
crackers, and fresh fruits. He requested a refill of a sedative, Ambien 10mg HS
prn, that he had been taking chronically for about a year. The physician
discussed the hazzards of chronic use with the patient but did not want to add
additional stresses on him. They aggreed to initiate tapering of the Ambien in
anticipation of discontinuation post radiation treatments. He complained of
somnolence produced by the lorazepam but continued to take it as prescribed for
the nausea. Two weeks after completion of his radiation therapy, right nasal
obstruction with epiphora was noted. He reported thick mucous bilaterally; but
otherwise was doing well. He continued to steam and irrigate using Bag Balm
ointment intranasally. Early in his radiation treatment he recorded in his
patient survey for fatigue that he was generally very active (professionally and
personally). He also noted that the fatigue he was experiencing was having a
"dramatic" impact on his energy level. In addition, he found it was harder to
concentrate as a result. Nutritional supplementation of Propax (3 packs per day)
was initiated in late June. He reported an improvement in his fatique levels by
day 5 of nutritional therapy with Propax and that he was able to tolerate the
nutritional therapy without stomach upset. This trend in improvement continued
through day 35 where he indicated that fatique no longer affected his daily
life. He noted dramatic improvements in his overall condition and that he able
to work 10 -12 hours daily. (See figure 2 for fatique survey).
In July of 1999, he developed adhesions and stenosis of the sinuses that
produced chronic sinusitis. He was given the antibiotic, Septra, for the
infection. However, he complained of vomiting and stomach cramping. The Septra
was discontinued and he was given Ceclor 500mg B.I.D for 14 days. He also
complained of nasal dryness for which a waterpik system was presented. He
returned to surgery in late July for re-biopsy of the nose to rule out tumor
recurrence. During this procedure uncinate processes, purulent ethmoid material
and anterior ethmoid cells were removed from the right nasal cavity. Significant
scar tissue was also removed from the right inferior nasal cavity. Diseased
mucosa of the right ethmoid was drained and removed. Additional biopsies were
obtained to evaluate for recurrence of the tumor. Pathology of the specimen
reported chronic sinusitis with inflammatory polyps and increased eosinophils.
Based on his fatique survey results, he was able tolerate the antibiotics
(without stomach upset) much better than he had previously been able to
tolerate. Seven months post radiation treatment, no major fatique was reported.
He continues to work 10 - 12 hours daily and credits Propax in making a
significant difference in his cancer treatment regimen.
In mid August, he was healing well with no evidence of tumor recurrence. In
addition, he had decreased supplementation of Propax to only one pack daily and
continued to maintain a significantly reduced level of fatigue as indicated on
his patient fatigue survey.
Discussion
There are fundamental biochemical differences in the composition of membrane
lipids (glycosphingolipids and phospholipids) between tumor cells and normal
cells(7,8,9,10,11). These differences may result from the aggressiveness of a
specific tumor to deplete the normal phospholipids of a normal cell membrane in
exchange for extrinsic phospholipids. Since phospholipids maintain membrane
integrity, regulate enzyme activities and processes, and possess other specific
functions, reduced levels may limit metabolic activity and available energy( 12,
13, 14, 15, 16,).
Similarly, as tumor cells sequester large amounts of phosphatidyl choline, an
imbalance in choline homeostais may result that could lead to muscle fatigue as
a result of decreasing plasma, brain, and muscle choline. This may account for
the malaise and chronic fatique reported to accompany certain types of cancers.
Therefore, oral exogenous supplementation may provide some benefit for fatigue.
Studies by Haubrich(17) and Cohen(18) reported that oral administration of
choline can elevate plasma brain and neuronal choline concentrations to release
acetycholine in the neuromuscular system. Since muscle function decreases during
choline deficiency(19), supplementation with phosphatidyl choline may compensate
for the deficiency(20).
In addition, the protective effects of fat-soluble and other natural
antioxidants are well known(21). These antioxidant defenses are important in
determining immune cell integrity and functionality of membrane lipids, cellular
proteins, and nucleic acids. Additionally, antioxidants are believed to control
signal transduction and gene expression in immune cells(22). There are several
stages where antioxidants may control the progression and malignancy of disease.
Antioxidants may also provide protection even when cancer-infected viral
activity is present (22).
Therefore, dietary introduction of these nutrients may stimulate host
immunological defenses and damage malignant cells directly by cycling with
consequent oxygen radical production. The unique dietary supplement, Propax,
addresses the nutritional concerns of oncology patients without resorting to
mega dosing as in many immunosuppressive types of disease states. The
formulation is composed of the complete antioxidant group and trace minerals,
combined with water-soluble nutrients and essential fatty acids. To aid in the
production of ATP, the formulation also includes phospholipids & creatinine,
creatinine phosphate, tyrosine, and alpha glutarate. Finally, the formulation
utilizes a unique delivery system that mimics the way the body utilizes
nutrients by improving cell maintenance and metabolic activity of normal
cells(23).
Radiation in combination with surgery is considered standard of therapy for
adenoid cystic carcinoma and has been associated with better survival
outcomes(24,25,26). However, radiotherapy is associated with several physical
and psychological symptoms, especially during treatment periods(27). Evidence
suggests fatigue may be more profound upon completion of therapy as opposed to
its initiation(28). However, this was not the case for the patient discussed
here. His fatigue actually improved throughout his radiation therapy.
The pain and fatigue as experienced by this patient is not uncommon(29). Both of
these physical symptoms improved over the course of treatment. Additionally,
sleep disturbances similar to that encountered by this patient is also common
and may require a sedative to facilitate sleep(30). Although predicting symptoms
like fatigue in patients is difficult, evidence does suggest that a patient's
understanding of fatigue and physical condition pre-treatment with radiation may
also affect the perception of fatigue as experienced by the patient(31). This
may have contributed to the positive results of this study as his general mental
well-being throughout radiation therapy was optimistic. This is supported by the
recent work of Lilleby et al who stressed a significant importance on the
overall general well being of patients. In fact, general quality of life issues
such as physical function, emotional function and fatigue were of greater
significance to the patient than other issues like sexuality or probablility of
infection (32). Lovely and colleagues concluded similar results by reporting an
inverse relationship between quality of life and fatigue (33).
These properties may be of benefit in treating the fatigue and malaise commonly
seen in patients with immunosuppressive disease, similar to the one previously
described. Although, well-controlled, blinded, clinical studies are required to
draw definitive conclusions on the effectiveness of nutritional supplements like
Propax, it may correlate with the positive results for decreased fatigue and
stomach upset experienced by the patient.
Figure 1. Summary of differentials during treatment regimens.
Figure 2. Summary of fatigue indicators per patient survey.
Legend: 1 = Does your tiredness / fatigue keep you from doing your housework /
job/ work?
2 = Does your fatigue keep you from your social life?
3 = Do you take naps everyday because of tiredness / fatigue?
4 = Does your fatigue interfere with your mental focus?
Rated 1 thru 5: 1 = None of the time
2 = Part of the time
3 = Half of the time
4 = Most of the time
5 = All of the time
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