I will take up this question in two parts [culled from a recent review I completed], first examining defensive and proactive measures to address and remediate cancer-related anorexia-cachexia, and the examining issues of diet and nutrition in stomach cancer to help optimize survival:

Modulating Cancer Anorexia-Cachexia Syndrome (CACS)

Cancer anorexia-cachexia syndrome (CACS), with its associated obstruction to swallowing, early satiety, nausea and vomiting, and particularly weight loss secondary to both physical anatomical sequelae as well as the co-existence of systemic inflammation, is indisputably one of the most commonly encountered and devastating problems impacting patients with advanced malignancies, especially GI cancers including gastric and stomach cancer. Parenteral nutrition and enteral nutrition, alone or used in combination, remaining the best-evidenced and most effective methods in the perioperative and palliative management of cachectic stomach cancer patients, with the choice between parenteral nutrition (PN) and enteral nutrition (EN frequently made on an individual bases given unique needs, preferences and co-morbidities [1].

But we have recently seen important new and emerging breakthroughs in addressing cancer anorexia-cachexia syndrome (CACS), especially (1) endocrine agents, (2) antioxidants, and (3) NSAIDs/COX inhibitors, discussed below:

As demonstrated in a recent phase III, randomized non-inferiority trial [2], megestrol (Megace) although it does no typically result in increased muscle mass or improvement in performance status, nonetheless can improve appetite, calorie intake, weight gain, and sense of well-being in cancer patients, also confirmed in a recent Cochrane Review [3], and further confirmed in a comparative randomized controlled trial (RCT) [4] of the efficacy of three different treatment modalities in the management of cancer cachexia, namely (1) megesterol acetate (MA) plus the NSAID meloxicam, (2) MA plus meloxicam plus oral eicosapentaenoic acid (EPA)-enriched nutritional supplement, or (3) meloxicam plus oral EPA-enriched nutritional supplement, finding that either:

MA plus meloxicam

OR

EPA supplement plus meloxicam are effective treatment options in the management of cancer cachexia, and that adding all three provides no additional significant benefit.

As to antioxidants, multimodal phase II trials [5,6] of antioxidant combinations like α-lipoic acid, carbocysteine lysine salt, and vitamins E, A and C demonstrated considerable benefit, and this combination multi-target therapies point of view appears to more often promote desirable outcomes than single agents, as confirmed by a large five-arm study [7] in which patients were prescribed oral antioxidant supplementation plus either medroxyprogesterone acetate (MPA) or megestrol acetate (MA), along with eicosapentaenoic acid (EPA)-enriched nutritional supplement, plus carnitine or thalidomide. It was demonstrated that the combination therapy elicited improved response over each component given in isolation, suggestive of potentially synergistic effect.

But this introduction of concurrent multi-targeting therapies can increase the risk of adverse interactions, and the greater degree of polypharmacy may be a considerable medical and financial burden on patients, that may unfortunately increase the likelihood of non-adherence [8]. Therefore, I would advocate a combination but more minimalist approach, as exemplified in a recent study [9] where the amino acid carnitine, the anti-inflammatory COX-2 inhibitor celecoxib, and the endocrine agent megestrol acetate (MA) were evaluated as combination regimen. What the trial found was carnitine plus celecoxib without any megestrol acetate was non-inferior to all three in combination. Therefore, as the authors wisely concluded, this simple, feasible, effective, safe, low cost with favorable cost-benefit profile, two-drug approach could be suggested in the clinical practice to implement CACS treatment".

In addition the omega-3 fatty acid component eicosapentaenoic acid (EPA), has been demonstrated in human clinical trials [10] to significantly reduce the production of cytokines and the concentration of CRP and PIF, and to improve overall weight and functional status, as well as increase appetite in refractory cancer cachexia patients. Furthermore, in contrast to megestrol acetate (MA), EPA improved lean body mass, ad this has been cross-confirmed in another study [11] that demonstrated EPA compared highly favorably against megestrol acetate (MA) as to overall weight gain, increased survival and improved QoL. Finally additional human clinical data shows that EPA’s amelioration of cachexia is enhanced in the presence of a targeted exercise regime [12,13], strongly motivating the inclusion of physical activity in multimodality therapies of cancer anorexia-cachexia syndrome (CACS).

Modulating Survival

Recent human clinical data shows that certain dietary factors and vitamins may influence the survival rate of people with stomach cancer [14], with patients in the top one-third for vitamin E intake being 25% more likely to survive for ten years. In addition, when only patients with a family history of stomach cancer were considered, survival rates were dramatically reduced in those patients with diets in the top one-third for animal protein, animal fat, and N-nitrosodimethylamine (a byproduct of cooking, especially high-heat, of meats), clearly showing that animal-fat intake is significantly associated with worse outcomes in the patients with a family history of stomach cancer, in contrast to a 50% mortality rate reduction for patients in the top one-third for vegetable fat or starch intake. This study also found a relationship between dietary vitamin E and improved chances of survival from stomach cancer, and this was already demonstrated earlier when Vitamin E was administered with selenium and beta-carotene [15], true also of other malignancies such as pancreatic cancer [18]. Of course, it still remains to be demonstrated whether changing the diet after the cancer diagnosis would materially affect survival. Further mature human clinical data, now pending, will clarify this issue more decisively.

METHODOLOGY OF THE REVIEW

A search of the PUBMED, Cochrane Library / Cochrane Register of Controlled Trials, MEDLINE, EMBASE, AMED (Allied and Complimentary Medicine Database), CINAHL (Cumulative Index to Nursing and Allied Health Literature), PsycINFO, ISI Web of Science (WoS), BIOSIS, LILACS (Latin American and Caribbean Health Sciences Literature), ASSIA (Applied Social Sciences Index and Abstracts), and SCEH (NHS Evidence Specialist Collection for Ethnicity and Health) was conducted without language or date restrictions, and updated again current as of date of publication, with systematic reviews and meta-analyses extracted separately. Search was expanded in parallel to include just-in-time (JIT) medical feed sources as returned from Terkko (provided by the National Library of Health Sciences - Terkko at the University of Helsinki). Unpublished studies were located via contextual search, and relevant dissertations were located via NTLTD (Networked Digital Library of Theses and Dissertations) and OpenThesis. Sources in languages foreign to this reviewer were translated by language translation software.

REFERENCES

1. Stojcev Z, Matysiak K, Duszewski M, Banasiewicz T. The role of dietary nutrition in stomach cancer. Contemp Oncol (Pozn) 2013; 17(4):343-345.

2. Madeddu C, Dess? M, Panzone F, et al. Randomized phase III clinical trial of a combined treatment with carnitine + celecoxib ± megestrol acetate for patients with cancer-related anorexia/cachexia syndrome. Clin Nutr 2012; 31: 176-82.

3. Ruiz Garcia V, López-Briz E, Carbonell Sanchis R, Gonzalvez Perales JL, Bort-Marti S. Megestrol acetate for treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev 2013; 3:CD004310.

4. Kanat O, Cubukcu E, Avci N, et al. Comparison of three different treatment modalities in the management of cancer cachexia. Tumori 2013 Mar-Apr; 99(2):229-33.

5. Mantovani G, Madeddu C. Cyclooxygenase-2 inhibitors and antioxidants in the treatment of cachexia. Curr Opin Support Palliat Care. 2008;2:275–81.

6. Mantovani G, Maccio A, Madeddu C, Gramignano G, Lusso MR, Serpe R, et al. A phase II study with antioxidants, both in the diet and supplemented, pharmaconutritional support, progestagen, and anti-cyclooxygenase-2 showing efficacy and safety in patients with cancer-related anorexia/cachexia and oxidative stress. Canc Epidemiol Biomarkers Prev. 2006;15:1030–4.

7. Mantovani G, Maccio A, Madeddu C, Serpe R, Massa E, Dessi M, et al. Randomized phase III clinical trial of five different arms of treatment in 332 patients with cancer cachexia. Oncologist. 2010;15:200–11.

8. Maggiore RJ, Gross CP, Hurria A. Polypharmacy in older adults with cancer. Oncologist. 2010;15:507–22.

9. Madeddu C, Dessì M, Panzone F, Serpe R, Antoni G, Cau MC, et al. Randomized phase III clinical trial of a combined treatment with carnitine + celecoxibmegestrol acetate for patients with cancer-related anorexia/cachexia syndrome. Clin Nutr. 2012;31:176–82.

10. Laviano A, Muscaritoli M, Rossi Fanelli F. Phase II study of high-dose fish oil capsules for patients with cancer-related cachexia: a Cancer and Leukemia Group B study. Cancer. 2005;103:651–2.

11. Jatoi A, Rowland K, Loprinzi CL, Sloan JA, Dakhll SR, MacDonald N, et al. 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. J Clin Oncol. 2004;22:2469–76.

12. Tiryaki-Sönmez G, Schoenfeld B, Vatansever-Ozen S. Omega-3 fatty acids and exercise: a review of their combined effects on body composition and physical performance. Biomed Hum Kinet. 2011;3:23–9.

13. Penna F, Busquets S, Pin F, Toledo M, Baccino FM, López-Soriano FJ, et al. Combined approach to counteract experimental cancer cachexia: eicosapentaenoic acid and training exercise. J Cachexia Sarcopenia Muscle. 2011;2:95–104.

14. Palli D, Russo A, Saieva C, et al. Dietary and familial determinants of 10-year survival among patients with gastric carcinoma. Cancer 2000;89:1205–13.

15. Blot WJ, Li JY, Taylor PR, et al. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst 1993;85:1483–92.

16. Meyer F, Bairati I, Shadmani R, et al. Dietary fat and prostate cancer survival. Cancer Causes Control 1999;10:245–51.

17. Gregorio DI, Emrich LJ, Graham S, et al. Dietary fat consumption and survival among women with breast cancer. J Natl Cancer Inst 1985;75:37–41.

18. Carter JP, Saxe GP, Newbold V, et al. Hypothesis: dietary management may improve survival from nutritionally linked cancers based on analysis of representative cases. J Am Coll Nutr 1993;12:209–26.

19. Greenlee RT, Murray T, Bolder S, Wingo PA. Cancer statistics, 2000. CA Cancer J Clin 2000;50:7–33.

20. Greenlee RT, Murray T, Bolder S, Wingo PA. Cancer statistics, 2000. CA Cancer J Clin 2000;50:7–33.

Thank you Kaniklidis for your detailed answer. I think vitamins are greatly needed as you refering to vit. A, E, , ... I thought Vit. D could be of great interest for Stomach cancer patients ( they are suffeciently exposed to the sun light and may even have reactions to sun ligh). What do you think of this?

Dear El-Hassan:

Excellent question and shrewd observation!, and although the results to date are not as yet dispositive, they are highly plausible:

An early prospective study found that higher vitamin D status were non-statistically-significantly associated with a lower risk of stomach cancer [1]. In addition, solar radiation/latitude studies [2], and higher vitamin D exposure index studies [3] have shown that higher vitamin D levels were associated with lower risk of stomach (and esophageal) cancer, and this has been further confirmed in a recent review [4].

In addition, a recent Chinese study [5] observed Vitamin D status in gastric cancer patients, finding that only 8.1% patients reached sufficiency level while up to 57.9% patients were in the deficiency range, and further found that clinical stage as well as lymph node metastasis classification were both inversely associated with vitamin D levels. Indeed, patients with high vitamin D levels group (≥ 50 nmol/L) had a higher overall survival compared with the low vitamin D levels group (below 50 nmol/L), and multivariate analysis indicated that vitamin D levels were an independent prognostic factor of gastric cancer.

Note that collectively these findings suggest that Vitamin D levels are prognostic in gastric cancers, although it remains for prospective RCTs to demonstrate whether Vitamin D supplementation will prove to be not just prognostic and preventive, but therapeutically beneficial in active stomach malignancy. Nonetheless it would appear prudent to assure Vitamin D adequacy in all gastric cancer patients until mature data established more decisively the precise range of optimality for therapeutic effect.

REFERENCES

1. Giovannucci E, Liu Y, Rimm EB, Hollis BW, Fuchs CS, Stampfer MJ. et al. Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst. 2006;98:451–459.

2. Grant WB. An estimate of premature cancer mortality in the US due to inadequate doses of solar ultraviolet-B radiation. Cancer. 2002;94:1867–1875.

3. Giovannucci E, Liu Y, Rimm EB, Hollis BW, Fuchs CS, Stampfer MJ. Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst. 2006;98:451–459.

4. Hargrove L, Francis T, Francis H. Vitamin D and GI cancers: shedding some light on dark diseases. Annals of Translational Medicine 2014; 2(1).

5. Ren C, Qiu MZ, Wang DS, et al. Prognostic effects of 25-hydroxyvitamin D levels in gastric cancer. J Transl Med 2012; 10:16.

Thanks for the comprhensive discussion, was very helpful to me. As this subject touches a family member, this discussion brings me a psychologic comfort as well.