August 2004

Dear Readers: Here's the Article for this Month:

Name of article:

An Eicosapentaenoic Acid Supplement versus Megestrol Acetate Versus Both for Patients with Cancer-associated Wasting: A North Central Cancer Treatment Group and National Cancer Institute of Canada Collaborative Effort

Author(s): Jatoi A, Rowland K, Loprinzi CL, Sloan JA, Dakhil SR, MacDonald N et al.

Abstract: J Clinical Oncology 2004; 22: 2469-2476

Eicosapentaenoic Acid (EPA) is an essential omega-3 fatty acid highly present in certain species of fish. Published studies showed that EPA administration in patients with cancer-associated wasting brought about weight stability as well as weight gain, an increase in appetite and an increase in survival. From data of translational studies, EPA seems to suppress some mediators of cancer-associated wasting such as interleukin-6 and a proteolysis-inducing factor (inducing protein degradation).

Jatoi et al. carried out a double-blind, placebo-controlled trial which compared three treatment arms: an EPA nutritional supplement (1.9 g bid) plus placebo; megestrol acetate (MA) 600 mg/day plus an isocaloric, isonitrogenous placebo twice a day; and both agents. The aim of this multi-centre trial was to evaluate which therapy improved weigh, appetite, quality of life and survival.

MA was included in the study because it proved to increase appetite and non fluid weight in cancer patients, a nutritional supplement was included because one study showed that a combination of this caloric supplementation to EPA lead to weight gain.

Patients with brain tumors, brain metastases, potentially hormone-sensitive tumors, ascites or oedema, GI problems, heart failure, history of thromboembolism and those with a life-expectancy < of 3 month were excluded from this study, in addition to patients treated with steroids, progestinics and other appetite stimulants.

For the inclusion in the study, patients were required to have a 2-month weight loss of at least 5 lb (2.3 Kg) and they had to perceive loss of weight and/or appetite as a problem. A total of 421 patients were considered assessable.

Regarding WEIGHT, the percentage of patients treated with MA alone who reached the 10% weight gain above baseline (primary end point) was higher than that of patients treated with EPA supplement (18% vs 6% p=.004). Combination therapy resulted in weight gain of >= 10% in 11% of patients (p=.17 across all arms).

APPETITE measured by the North Central Cancer Treatment Group (NCCTG) questionnaire was unable to detect any difference among the three therapeutic arms. Differently, using the Functional Assessment of Anorexia/Cachexia (FAACT) questionnaire (version 4), appetite stimulation was reported to be higher in MA alone arms and in EPA-MA arm compared with the EPA supplement alone arm (p=.004).

Regarding global QUALITY OF LIFE and SURVIVAL no significant difference among the groups was found.

TOXICITY among the study arms was comparable. However, male patients in the arms including MA reported greater rates of impotence (which was however not evaluated at basal time).

Why I chose this article

Lack of appetite and loss of weight are present in most advanced and terminal cancer patients. Whilst we know MA’s value in stimulating appetite and weight increase, data relative to EPA’s role are still wanting. Bruera recently studied the efficacy of fish oil in 60 patients with advanced cancer and demonstrated its inefficiency. Jatoi’s RCT results are an additional confirmation, i.e. EPA supplement does not give any significant improvement as far as weight, survival or quality of life are concerned when compared with Megestrol Acetate.

Regards,

Carla Ripamonti, MD
Member of the Board of Directors, IAHPC