Non-Invasive Assessment of Skeletal Muscle Loss in Cancer Patients - Phase II

The long-term objective of this research is to develop a non-invasive approach for
assessment of de novo 3MH production in cancer patients early in the course of the disease
as a way of assessing which patients are at high risk for future development of skeletal
muscle atrophy. The approach is based on: 1) the known increase in de novo production of
3-methylhistidine (3MH) from muscle protein breakdown in said patients as a consequence of
their unique disease-host interactions, and 2) earlier demonstration that de novo 3MH
production can be measured in vivo using isotope dilution.

During this Phase-II project, we propose to conduct a statistically powerful prospective
investigation to demonstrate that measurement of the slope of the terminal decay curve (rate
constant) with our approach in newly diagnosed cancer patients predicts future development
of muscle wasting. We expect the outcome of the combined Phase-I and Phase-II research to
lead to the early identification of elevated muscle catabolism in at-risk patients so that
medical intervention can prevent future muscle atrophy.

Inclusion Criteria:

- (1) histological or cytological evidence of NSCLC without curative options;

- (2) over 18 years of age;

- (3) patient reported weight loss of ≤5% of usual body weight in the last 6 months;

- (4) life expectancy of greater than 6 months based on the judgement of treating
physician;

- (5) serum creatinine ≤1.5 times the upper limit of normal; and

- (6) willing and able to give informed consent.

Exclusion Criteria:

- 1) malabsorption, intractable vomiting or gastrointestinal obstruction

- 2) congestive heart failure

- 3) edema or ascites

- 4) liver function test results that will preclude administration of prescribed
therapy

- 5) pregnant, nursing, or, if of child-bearing age, unwilling to use contraceptives