Low Antioxidant Diet in Controlling Cachexia in Patients With Oropharyngeal Cancer Receiving Chemotherapy and Radiation Therapy

Phase I Randomized, Double-blind, Placebo-controlled Trial of the Effect of Temporary Dietary Antioxidant Depletion on Tumor Growth and Cachexia in Head and Neck Cancer Patients Receiving Chemoradiation Therapy

RATIONALE: Eating a diet that is low in antioxidants may control cachexia in patients with oropharyngeal cancer.

PURPOSE: This randomized phase I trial is studying the side effects of a low antioxidant diet in controlling cachexia in patients with oropharyngeal cancer receiving chemotherapy and radiation therapy.

OBJECTIVES:

Primary

• Determine the safety of the antioxidant-deficient diet (ADD) in controlling cachexia in patients with oropharyngeal cancer receiving chemoradiotherapy.

Secondary

• Determine the safety of the ADD as measured by quality of life, peripheral DNA damage, and change in body weight.
• Determine the effectiveness of the ADD on tumor growth and surrogate markers of tumor growth.
• Determine whether the ADD is effective in improving the tumor cachexia syndrome in these patients.
• Determine whether there is a serum metabolomic signature for the ADD.

OUTLINE: This a prospective, randomized, double-blind, placebo-controlled study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients consume a standard diet 3 times a day for 8 weeks.
• Arm II: Patients consume an antioxidant-deficient diet (ADD) 3 times a day for 8 weeks. Patients receive replacement vitamins in week 9.

All patients receive planned chemoradiotherapy in weeks 3-8.

Quality of life, body composition (by dual-energy x-ray absorptiometry), weight, and resting energy expenditure (by indirect calorimetry) are assessed at baseline and at week 8.

Blood samples are collected at baseline and at 8 weeks. Samples are evaluated for cytokine levels; evidence of DNA damage from peripheral blood lymphocytes; and serum signature characteristic to ADD by multinuclear MRI spectroscopy. Patients undergo a tumor biopsy in week 4 for research studies. Samples are collected and evaluated for generation of reactive oxygen species by using antibodies against oxidatively modified DNA and lipids; apoptosis using TdT-mediated dUTP nick-end labeling assay and classical morphological criteria; and levels of the tumor toxohormones lipid mobilizing factor and proteolysis inducing factor by real time-PCR, northern blotting, and western blotting methods.

After completion of study therapy, patients are followed once during weeks 9-12.

DISEASE CHARACTERISTICS:

• Biopsy-proven carcinoma of the oropharynx (regardless of primary diagnosis or recurrence)
• No active treatment for disease within the past 4 weeks

PATIENT CHARACTERISTICS:

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Feeding tubes allowed

• Prior malignancies allowed provided all of the following criteria are met:

  • Patient has undergone potentially curative therapy for all prior malignancies
  • There has been no evidence of any prior malignancies within the past 5 years (except for successfully treated cervical or non-melanoma skin cancer with no evidence of recurrences)
  • Patient is deemed by their treating physician to be at low risk for recurrence from prior malignancies

• Must be able to speak English

• Must have adequate home refrigeration

• No intractable vomiting

• No ascites or clinical/ultrasound evidence of fluid retention

• No uncontrolled hypertension

• No severe congestive heart failure

• No pneumonia

• No severe infections

• No known HIV positivity

• No coexisting medical condition that would preclude study compliance

• No decisionally-impaired individuals

• No history of abetalipoproteinemia (Bassen-Kornzweig syndrome)

• No history of spinocerebellar ataxia

• No history of chronic cholestatic hepatobiliary disease

• No history of diagnosed vitamin E deficiency

• No history of protein-energy malnutrition (marasmus or kwashiorkor)

• No history of disorders related to malabsorption (e.g., celiac disease, sprue, cystic fibrosis, duodenal bypass, congenital partial obstruction of the jejunum, obstruction of the bile ducts, giardiasis, or cirrhosis)

• No history of achlorhydria

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No concurrent parenteral nutrition