Short-Term Fasting: Impact on Toxicity

OBJECTIVES: I. To determine the safety and feasibility of short-term fasting prior to administration of combination chemotherapy with platinum in patients with advanced solid tumor malignancies. II. To evaluate the toxicity profile of platinum-based chemotherapy in subjects who eat normally compared to those who undertake short-term starvation. III. To investigate changes in plasma insulin, glucose, IGF1 and IGF binding protein (IGFBP) levels, and oxidative stress markers in subjects who undertake short-term fasting compared to controls. IV. To investigate whether changes in grp78 expression occur after fasting and after chemotherapy administration in human subjects. OUTLINE: STAGE I: Patients are assigned to 1 of 4 treatment groups. GROUP I: Patients fast for 24 hours on day-1. GROUP II: Patients fast for 48 hours on days -2 and -1. GROUP III: Patients fast for 72 hours on days -3, -2, and-1. GROUP IV: Patients undergo a modified 48-hour fast with minimal caloric intake on days -2 and -1. STAGE II: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients fast for 72 hours on days -2, and on day 1. ARM II: Patients proceed to chemotherapy without fasting. All patients receive gemcitabine hydrochloride intravenously (IV) on days 1 and 8 and cisplatin IV over 2 hours on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.