Nutritional support in multimodal therapy for cancer cachexia

Introduction Malnutrition has since long been known to be associated with adverse outcomes in cancer patients. The wasting in cancer cachexia involves loss of muscle and fat and reflects a catabolic metabolism induced by an abnormal host response to tumour presence and/or tumour factors. Patients with cancer cachexia frequently develop a chronic negative energy and protein balance driven by a combination of reduced food intake and metabolic change. Thus, alterations in both energy intake and components of energy expenditure may contribute to progressive weight loss. Increased resting energy expenditure related to the systemic inflammatory response is common and a sustained hypermetabolism over a long period of disease progression can make a large contribution to negative energy balance and wasting if not compensated for by an increase in energy intake. Hypermetabolism and diminished energy intake due to anorexia may thus constitute a vicious circle in the development of cancer cachexia. Discussion Though nutritional support alone can improve energy intake to a variable extent and for a variable period of time, it will not address the underlying catabolic metabolism and is thus likely to be of limited efficacy if attempts to attenuate the tumour-induced catabolic response are not carried out at the same time. Concomitant drug treatments for cancer cachexia may slow down the wasting process by reducing anorexia, attenuating the systemic inflammation, the skeletal muscle catabolism or stimulating the muscle protein anabolism. Thus, improved management of cancer cachexia may require a multimodal approach by a multi-disciplinary team and is best commenced earlier rather than later. Early start of therapy also facilitates the use of oral nutritional supplementation, which is preferable to parenteral nutrition in the majority of cases. Once a patient is severely wasted it may be neither practical nor ethical to intervene with anything else than supportive care. Conclusion An improvement in the condition of all patients with cachexia may not be possible, however, the goal must be to stabilise cachexia and prevent or delay further decline. There is currently no single or combined treatment strategy which is successful in all patients. However, strategies to counteract both hypermetabolism and reduced dietary intake have been demonstrated to be of importance for the survival, function and quality of life of cancer patients and should be further explored in interventional studies. Presented as invited lecture at the MASCC/ISOO 20th Anniversary International Symposium Supportive Care in Cancer in St. Gallen, June 2007.     

Setting performance goals In geriatric nursing

Behavioural techniques are increasingly being applied in the geriatric field as part of a broader emphasis on psychological and social treatments in the care of the elderly. The nurse is in the best position to analyse a patient's performance and manage an intervention programme; however, some nurses have had little experience of autonomously diagnosing problems and setting performance goals.
The authors argue that it is important to set such goals and give examples of how performance may be objectively specified, prerequisites made explicit, criteria for success defined and the consequences of goal attainment or non-attainment discussed with those most concerned.
A complex situation drawn from the geriatric setting which was used as part of a teaching workshop to help nurses define suitable targets for intervention is described in the Appendix.     

Life and treatment goals of patients with advanced,incurable cancer

Purpose

Goals of care conversations have been suggested as a strategy for helping patients with advanced cancer manage the uncertainty and distress associated with end-of-life care. However, knowledge deficits about patient goals limit the utility of such conversations. We described the life and treatment goals of patients with incurable cancers, including goal values and expectancies. We examined the associations between paramount goals and patient prognosis, performance status, and psychological adjustment.

Methods

Patients with advanced lung cancer, gastrointestinal cancer, or melanoma (N?=?84) completed measures of prognosis for 12-month survival, hope, optimism, depression, and anxiety. Oncologists provided patient performance status and prognosis for 12-month survival. We conducted interviews with a subset of patients (N?=?63), eliciting life and treatment goals, values, and expectancies.

Results

Patient life goals resembled goals among healthy populations; whereas, treatment goals were perceived as separate and more important. Cure and fight cancer emerged as the most important goals. Patients who valued cure the most had worse performance status (M?=?1.46 vs. 0.78) and more depressive symptoms (M?=?6.30 vs. 3.50). Patients who valued fight cancer the most had worse self-prognosis (M?=?69.23 % vs. 86.11 %), fewer treatment goals (M?=?2.08 vs. 3.16), and lower optimism (M?=?15.00 vs. 18.32).

Conclusions

Patients with advanced cancer perceive treatment goals as separate from and more important than life goals. They hold optimistic expectancies for achieving their goals and for survival. Valuing cure highly may put patients at risk for experiencing psychological maladjustment.

     

Evaluation of photodynamic therapy in advanced gastrointestinal cancer

One hundred forty-two patients with advanced gastrointestinal cancers were treated by PDT from September 1982 to December 1988. Hematoporphyrin derivative (HpD) (5 mg/kg) was given intravenously 48-72 hours before PDT. The light source was an argon dye laser with an output beam of 630 nm. The entire tumor was irradiated with a light dose of 100-250 J/cm 2. Fifteen patients (10.6%) had a complete response, 53 (37.3%) had a partial response, and 32 (22.5%) had a mild response. In all, 100 patients (70.4%) had a response to PDT. The experiments and clinical results show that the estimated energy dose (EED) value 200-250 J/cm 2 is appropriate. All patients were treated by PDT and adjuvant chemotherapy and showed good results with a follow-up of 1-5 years. Thirteen of 15 patients in the CR group are alive (86.7%), and 12 patients survived more than 2 years (8.8%).     

Why targeted therapy hasn't worked in advanced cancer

In this issue of the JCI, Nissen et al. report that a reciprocal interaction exists between the growth factors FGF2 and PDGF-BB, causing tumors to exhibit increased angiogenesis and metastatic potential. Both FGF2 and PDGF-BB signal through tyrosine kinase receptors, which have been the target of tyrosine kinase inhibitors for cancer therapies. These inhibitors are usually small molecules that inhibit the kinase activity of a receptor or nonreceptor tyrosine kinase, preventing downstream signaling. The results of this study shed light on why tyrosine kinase inhibitors have been useful for the treatment of only a small number of advanced cancers. Currently, a major focus of pharmaceutical companies is to develop ever more potent and specific tyrosine kinases. The results presented here suggest that this approach may not be successful.     

非小细胞肺癌的靶向治疗

肺癌的发病率和死亡率在全球恶性肿瘤中居首位。其中,非小细胞肺癌（NSCLC）占80%~85%。绝大多数NSCLC在临床确诊时正处于复发或转移性的晚期阶段,化疗是这部分人群的主要治疗手段。但是,作为标准一线治疗的含铂两药联合化疗方案已进入平台期,无进展生存期（PFS）为4~6个月,总生存期（OS）仅为8~10个月。近年来,靶向药物的临床应用让人们看到了跨越这一平台的希望和曙光,靶向治疗作为一支生力军正逐渐登上非小细胞肺癌综合治疗的历史舞台。     

Gefitinib therapy for advanced non-small-cell lung cancer

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and toxicity of gefitinib in non-small-cell lung cancer (NSCLC). DATA SOURCES: Primary literature search through MEDLINE and CANCERLIT, and abstract presentations (1966-May 2003). STUDY SELECTION AND DATA EXTRACTION: All published trials and abstracts citing gefitinib were evaluated, and all information deemed relevant was included in this article. DATA SYNTHESIS: NSCLC is known to overexpress epidermal growth factor receptor (EGFR). Gefitinib is a selective EGFR tyrosine kinase inhibitor. Based on the Phase I/II trial results, the optimal dose is 250 mg/d orally. It is well tolerated, with minimal and reversible toxicity. Skin rash and diarrhea are the most common adverse effects. Recent trials have shown that gefitinib provided a 10% tumor response rate and improved disease-related symptoms in patients with refractory, advanced NSCLC. CONCLUSIONS: Gefitinib, with a unique mechanism of action and favorable toxicity profile, has demonstrated clinical activity in NSCLC patients with chemotherapy-refractory disease. It provides a valuable addition to the treatment options as monotherapy in patients with advanced NSCLC after failure of both platinum-based and docetaxel chemotherapies. Further research is required to evaluate the use of gefitinib in different clinical settings.     

进展期胃癌的分子靶向治疗

过去的二十年里,进展期胃癌患者通过治疗后可以改善生活质量及延长生存期,但是其治疗方法并没有获得显著进展。虽然胃癌的中位生存期大约在7~11个月,且存活超过2年的已经〉10%,但是,对于进展期胃癌患者来说,其最合适的一线化疗方案一直存在争议,且大多数人对化疗仍持有偏见。最近,肿瘤生物学的显著进展促进了靶向致癌关键途径的新药物研究。在国际随机研究中,对进展期胃癌来说,多数分子靶向因子被证实有效,一种抗HER-2单克隆抗体（曲妥珠单抗）显示在抗HER-2阳性的进展期胃癌方面有抗肿瘤活性。然而,只有20%的HER-2阳性的进展期胃癌患者在此获益。因此,发展更有效的因子和鉴别预测及预后的标记物因子来选择哪些患者能从特定的化疗方案和靶向治疗中获益显得至关重要。本文就进展期胃癌的靶向治疗作一综述。     

Nutritional therapy in diabetes. Rationale and recommendations

The cornerstone of diabetes management is an appropriate diet. Various diets, including one low in carbohydrate, have been recommended in the past. The American Diabetes Association currently recommends a diet high in complex carbohydrate and fiber. The diet plan should be individualized. Caloric content is based on the patient's body build, weight, energy needs, and activity and may be adjusted according to individual eating habits, type of insulin regimen, and metabolic derangements. The proportion of caloric sources (fat, carbohydrate, protein) may be altered depending on the presence of secondary disorders. Several small daily meals, including a bedtime snack, are advised. Diabetic diets are often cost-effective, contrary to common belief. Patients should be encouraged to exercise to achieve optimum diabetic control. Active patient participation in the management program is an essential component of therapy.     

Clinitron therapy and pain management in advanced cancer patients

Many patients with advanced malignancy develop bone metastases, pathologic fractures, and skin breakdown, all of which compromise comfort and interfere with the delivery of patient care. In 1986, 38 Clinitron beds were utilized at Calvary Hospital, a specialty hospital for advanced cancer, for patients who were immobile and/or had significant pain. Twenty-five patients were entered into an open study to assess and document this experience. Twenty-two patients experienced improved comfort while Clinitron therapy was in use. Global questionnaires relating to pain, comfort, appetite, and sleep were completed by the patients, their primary nurses, and attending physicians. No adverse effects were noted. The results suggest that Clinitron therapy is effective in promoting comfort in select advanced cancer patients. The difficulties encountered in research in this patient population are presented.