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1.1
Treatment
1.11
Cancer anorexia and cachexia are multifactorial problems
that affect up to 87% of patients
with some malignant diseases (Laszlo
and Dekken,1986). Contributing factors to these problems
include (Laszlo and Dekken,1986)
local effects of the cancer (e.g. gastrointestinal obstruction),
(Klein
et al., 1986) systemic effects of malignant disease
that may suppress appetite centrally, increased basal metabolic
rate, or alter substrate utilization more (Nixon,
1986) and local or systemic effects of cancer treatment.
Cachexia has been blamed for 22% of cancer deaths in a series
of 400 autopsies and was implicated as an ancillary contributor
to death in many additional patients (Laszlo
and Dekken,1986). Nutritional impairment correlates
with the response to therapy and may be directly related
to therapeutic results and severity of treatment-related
toxicity.
1.12
Multiple interventions have been attempted to try to treat
cancer anorexia and cachexia. Enteral and parenteral nutrition
procedures will increase caloric intake but these methods
are cumbersome, expensive, and uncomfortable. In randomized
trials they have not been clearly demonstrated to improve
long-term outlook for cancer patients or the immediate results
of specific treatment interventions (Klein
et al.,1986; Nixon,
1986). A simple nontoxic medical reversal of cancer
anorexia and cachexia would be of considerable value in
the symptomatic and supportive management of the cancer
patients and could possibly supplement effectiveness of
other therapeutic efforts. In 1987, the NCCTG and Mayo Clinic
initiated a trial studying cyproheptadine in patients with
cancer anorexia and cachexia. This trial suggested that
there was a mild appetite stimulation from cyproheptadine
but this did not translate into any significant positive
weight gain (Kardinal
et al., 1990).
1.13
Megace (megestrol acetate) is a progestational agent that
is frequently used at a dose of 160 mg/d in women with metastatic
breast cancer. It is generally well tolerated in the vast
majority of patients with the exception being that it may
cause undesirable weight gain (Gregory
et al.,1985; Benghiat
et al.,1986; Tchekmedyian,
1987). Twenty-seven of 28 breast cancer patients, treated
with higher than usual doses of Megace (480-1600 mg/d) for
6 weeks or more, gained a median of 5.1 kg (0.9-20.1 kg)
(Tchekmedyian,
1987).
1.14
This weight gain effect seen in breast cancer patients has
led to the use of megestrol in non-breast cancer patients
with cancer cachexia (Tchekmedyian,
1987). Nine of 33 such patients gained more than 2.3
kg and 14/33 reported a subjective improvement in their
sense of well-being when conventional doses (160 mg/d) of
megestrol were used. In 1978, a randomized adjuvant trial
of Megace (320 mg/day) versus observation was started in
patients with resected primary melanoma at the Mayo Clinic.
Patients receiving Megace (320 mg/d) had a 6-month median
weight gain of 8.2 kg as opposed to a median weight gain
of 2.6 kg in the control group (p = 0.002) (Creagan
et al., 1989).
1.15
A pilot study of 14 AIDS patients who had lost 10% of their
body weight suggested that Megace was beneficial (von
Roenn et al., 1988). Patients on this trial gained significant
amounts of weight and reported an improved sense of well
being presumably related to Megace therapy. A randomized
trial of this drug in AIDS patients subsequently confirmed
that this drug leads to appetite stimulation and weight
gain.
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