Search

A working group on teaching palliative care in the home was convened at The National Consensus Conference on Medical Education for Care Near the End of Life. Our consensus statement includes: (1) a justification for education in the home; (2) general guidelines about teaching palliative care at this site; (3) identification of major barriers to training in the home, and some suggestions for overcoming these barriers; and (4) specific suggestions about how and what to teach. We find that the home is an excellent site for training in comprehensive palliative medicine. Housecalls afford an unusually rich and compelling opportunity to learn about the patient's and family's experience of severe illness and the impact of culture and environment on health care, and can have a broad humanizing effect on trainees. We propose that all medical students be familiar with this form of care. Trainees should learn the potential benefits and difficulties of managing terminal illness in the community, appreciate the role of health care teams in assuring safe, secure, high-quality care, and acquire the special knowledge, skills, and attitudes required for providing state-of-the-art palliative care for patients and families facing a terminal illness in the home, including for those dying at home. Instituting education in the home setting will require faculty development, support for more home visiting by physicians, and supervision of trainees in the home by other members of the health care team. Academic medical centers and hospice/home health agencies should collaborate to develop effective training programs.

The Canadian Palliative Care Education Group, a committee of the Canadian Society of Palliative Care Physicians, carries out surveys from time to time on the status of palliative care education in Canadian medical schools. We describe the organization of the Canadian Palliative Care Education Group and report on a survey carried out in the 1996–97 academic year. Our data suggest that the emphasis on palliative care varies widely amongst the 16 Canadian medical schools, in concert with the availability of academic staff positions in palliative care. We conclude that the need for palliative care education is supported by rhetoric which remains to be matched by proportionate tangible investment.

Diethylhexylphthalate (DEHP) is a phthalate plasticizer that belongs to the peroxisome proliferator (PP) class of rodent nongenotoxic hepatocarcinogens. Previously, we have shown that MEHP (a principal metabolite of DEHP and the proximal PP) induced DNA synthesis and suppressed apoptosis in rat but not in human hepatocytes in vitro. Here, we present further studies of species differences in response to DEHP. In rats, 4 days of exposure to DEHP (950 mg/kg per day by gavage) induced peroxisomal beta-oxidation, DNA synthesis and suppressed apoptosis. In contrast, there was no response of guinea pig liver to DEHP. In rat hepatocytes in vitro, MEHP (250, 500 and 750 microM) induced peroxisomal beta-oxidation, DNA synthesis and suppressed apoptosis. In contrast to the pleiotropic response noted in rat hepatocytes, there was no response of human hepatocytes to 250, 500 or 750 microM MEHP. PPs activate the peroxisome proliferator activated receptor alpha (PPARalpha) that binds to DNA at peroxisome proliferator response elements (PPREs) within the promoters of PP-responsive genes such as rat acyl CoA oxidase (ACO). However, the human ACO gene promoter differs at three bases within the PPRE from the rat ACO promoter and appears refractory to PPs. To address species differences in response to DEHP at the molecular level, we used promoter-reporter gene assays to compare the ability of MEHP to induce gene expression from the rat or the human ACO promoter. MEHP gave a concentration-dependent increase in reporter gene expression from the rat ACO gene promoter with either mouse or human PPARalpha. In contrast, the human ACO promoter was unable to drive MEHP-induced gene transcription irrespective of the species origin of PPARalpha. These data provide further weight of evidence at the cellular and molecular levels for a lack of risk to human health from the phthalate DEHP.

Peroxisome proliferators (PPs) are nongenotoxic rodent hepatocarcinogens that cause liver enlargement and hepatocarcinogenesis associated with peroxisome proliferation, induction of hepatocyte DNA synthesis and suppression of apoptosis. Acyl CoA oxidase (ACO) is a key enzyme of peroxisomal beta-oxidation and its transcriptional activation by PPs is often used as marker for the rodent response. PPs activate the peroxisome proliferator activated receptor-alpha, PPARalpha. Recent data suggest a role for tumour necrosis factor alpha (TNFalpha). This cytokine appears to be permissive for a PPARalpha-dependent growth response to PPs. Humans and guinea pigs appear to be nonresponsive to the adverse effects of PPs noted in rodents. These species differences can be attributed to reduced quantity of full length functional PPARalpha in human liver and evidence supports the presence of a truncated form of PPARalpha, hPPARalpha8/14 in human liver. In addition, species differences could be attributed to qualitative differences in the PPARalpha-mediated response because the promoter for human ACO differs in sequence and activity from the rat equivalent. These data contribute to our understanding of how chemicals may cause tumours in rodents and how this response may differ in humans.

Reaction of [Ru3Pt(µ-H)(µ4-η2-CCBut)(CO)9(L2)]la(L2= dppe) with Ph2PCCPPh2 affords the butterfly cluster [Ru3Pt(µ-PPh2)(µ4-η2-CCBut)(CO)7(dppe)]3; the metal skeleton and µ4-η2 alkynyl coordination mode in 3 represent a likely model for a transition geometry in the interconversion of 1 and its vinylidene tautomer [Ru3Pt{µ4-η2-CC(H)But}(CO)9(L2)]2.

Palliative care has primarily addressed the needs of patients with cancer during their last days of life. Indeed, in one country, it is mandated that formal hospice programs can only enroll patients who are expected to die within 6 months. The model wherein palliative care works only with cancer patients and their families towards the end of the patients’ existence is not logical, and may be expected to change dramatically over the next 10 years. Data from the SUPPORT study [1] clearly indicate that aspects of suffering common to cancer are also uniformly noted in patients dying of other advanced chronic disorders. Moreover, symptoms at the end of life have their genesis earlier in the course of illness. For a number of these symptoms, including pain, the cachexia—anorexia syndrome, and delirium, evidence exists [2–5] that early diagnosis and impeccable management may prevent or alleviate the full flowering of a devastating symptom. Logically, the myriad psychosocial problems that come to the fore during the course of illness should also be recognized and addressed before the end stage of an illness.

Peroxisome proliferators (PPs) form a discrete class of rodent non-genotoxic hepatocarcinogens (see Stringer, 1992 for review). These chemicals, which include industrially and pharmaceutically important compounds such as chlorinated solvents, plasticisers and hypolipidaemic drugs, have been the subject of intensive study over a number of years. Generally, following administration of PPs rats and mice undergo a range of responses including proliferation of peroxisomes in the liver and kidney, induction of certain hepatic enzymes, and liver enlargement. Although the vast majority of PPs are nongenotoxic by in vivo and in vitro criteria (reviewed in Ashby et al., 1994), these compounds cause the development of hepatocellular carcinomas when administered continually to rats and mice.

We report the analysis of a cancer management survey mailed to a representative group of health professionals in 1994. The goals of the study were to gather information on cancer pain treatment practices, and to obtain health professional views on obstacles to ideal pain management. The survey, designed by a working party of pharmacists, nurses and physicians, was distributed to 14,628 physicians. A total of 2,686 physicians responded to the survey, including 39% of medical or radiation oncologists, and 18.19% of physicians who listed their primary interest as Family Medicine. Reflecting the modest emphasis placed on palliative care and cancer pain management in the current Canadian milieu, 67% of physicians rated their past teaching experience as only "fair" or "poor." Lack of exposure to pain education was reflected in the response to a series of hypothetical case scenarios exploring physician choices in managing severe cancer pain. For example, in the initial management of a cancer patient with severe pain, 50% of physicians would not use a strong opioid in the absence of other contraindications to opioid use. A wide variety of analgesics and non-pharmacologic techniques is available to Canadian physicians to assist patients with pain. Few physicians identified the unavailability of analgesics or analgesic techniques as limiting factors in pain management. We condude that greater emphasis should be placed on pain education in our training programmes. We suggest that further surveys of this type, sponsored by our provincial colleges and medical organizations, can provide feedback which will enhance the adherence by Canadian physicians to published guidelines for pain management.

To evaluate the effectiveness of intravenous clodronate in ameliorating refractory bone pain in patients with metastatic bone disease, 60 patients with established osseous metastases and persistent bone pain were randomized to receive either clodronate (600 mg or 1500 mg in 500 mL of normal saline) or 500 mL of saline as placebo. After 2 weeks, the patients were crossed over to receive the alternate treatment. After another 2 weeks, each patient and investigator made a blinded choice. Daily visual analogue scales (VAS) and analgesic diaries were recorded throughout the study period. Forty-six patients were evaluable (77%). A treatment x period interaction was identified in the VAS and daily morphine equivalent dose (DMED) scores. First period analysis of the VAS scores for general pain, pain at rest, and pain upon movement demonstrated an average reduction of 13, 14, and 24 mm, respectively, from baseline, but were not significantly different from changes following placebo. The average change in DMED was -6.4 (SE = 2.9) following clodronate and was +24.6 (SE = 14.9) following placebo (p = 0.03). In the blinded choice of which agent resulted in improvement in pain, 26 (57%) patients chose clodronate, 12 (26%) chose placebo, and eight (17%) had no preference (p = 0.0021). For the investigators who also made a blinded selection, clodronate was chosen in 30 (65%) patients, placebo in ten (22%) patients, and no difference was apparent in six (13%) (p0.0001). Intravenous clodronate appeared to have analgesic effect in patients with refractory bone pain due to metastatic bone disease. The optimal dose and duration of effect require further evaluation, particularly in patients with stable disease and persistent bone pain.

e20598 Background: Post-treatment patients with active cancer face considerable burden from the effects of both disease and treatment. The Palliative Rehabilitation Program was designed to ease those challenges and to improve the patient’s functioning. The current study evaluated the changes in function scores of patients with advanced cancer upon completion of the structured program and examined the medical predictors of program completion. Methods: Referrals for 173 patients who were finished anticancer therapy were received. One hundred and thirty six patients were eligible and enrolled in the eight-week interprofessional palliative rehabilitation program. Of those, 84 completed the program. Measures of physical, nutritional, social and psychological functioning were evaluated at entry and completion of the program. Results: Significant improvements were experienced in physical performance (P =0.000), nutrition (P =0.000), symptom severity (P=0.005 to P= 0.000), symptom interference in functioning (P =0.001 to P=0.000), and fatigue (P=0.001 to P=0.000). Reasons for not completing the program were: disease progression, geographical inaccessibility, being too well, dying, and personal/unknown reasons. A normal CRP level (

We have been attempting to elucidate the molecular mechanisms through which peroxisome proliferators exert their pleiotropic effects, with particular emphasis on understanding why humans appear unresponsive to these compounds. There is a wealth of data to implicate the peroxisome proliferator-activated receptor alpha (PPAR alpha) in mediating these effects in rodent species; PPAR alpha is expressed in tissues that show physiological changes in response to PPs, is transcriptionally activated in vitro by a variety of PPs, and it has been recently demonstrated that mice lacking this receptor are refractory to the effects of clofibrate and Wy-14,643, at least in the short term. It is conceivable that differences in PPAR alpha between responsive rodent and unresponsive human subjects may provide the key to understanding the basis of this species variation in response, and with this in mind we have been studying the biology of PPAR alpha in humans and looking at interindividual variation. There is already published evidence, albeit on only two sequences, for structural and functional polymorphism in human PPAR alphas. We have extended these findings, and shown that: There is considerable variation in hPPAR alpha cDNAs obtained from different individuals, both at the gross structural level (lack of a coding exon) and of a more subtle nature (single base changes leading to amino acid substitutions). One such cDNA, the sequence of which differs at only three amino acids from that published, encodes a receptor that is incapable of transcriptional activation by potent PPs. The degree to which hPPAR alpha transcripts are expressed in human livers can vary by up to an order of magnitude between individuals. The tissue-specific expression profile of PPAR alpha in humans is very different from that in rat and mouse. In particular, the human liver contains generally low levels of PPAR alpha in contrast to the responsive rodents, in which potent PPs cause liver tumors. Taken together, these data suggest first that human and rodent PPAR alphas differ according to a number of molecular and biochemical criteria, and secondly that there is a degree of interindividual variation in PPAR alpha structure and function. Studies are ongoing to clarify this further, but human polymorphism may go some way towards explaining the apparent paradox that active PPAR alpha receptors can be isolated from an "unresponsive" species.

e18098 Background: For modern evidence-based medicine, a well defined risk scoring system on survival has important clinical implications for identifying patients with a poor prognosis. The objective of this study was to develop a Montreal Prognostic Score (MPS) based on risk scores of the baseline clinical markers. Methods: A training Cohort (TC) and confirmatory cohort (CC) of patients with non small-cell lung cancer were used to develop a Montreal Prognostic Score (MPS) and were assembled of patients from 3 different oncology centres: Jewish General Hospital in Montreal, Quebec, Canada; the University General Hospital of Heraklion Crete, Greece; and at the University General Hospital of Larissa, Greece. Stage, performance status, smoking status, CRP, Albumin, LDH and WBC from TC were entered in a Cox’s model on survival. Independent prognostic factors (p ≤ 0.1) were assigned a relative risk score by dividing their Proportional Hazard by the lowest one rounding to the closest integer. A 3 risk groups’ regression based total score (MPS) was finally developed by regrouping subgroups of patients with similar median survival. The MPS was tested on the CC. C-statistics was used to test the accuracy of the MPS. Results: 638 pts were included in the study: 314 in the TC and 324 in the CC. Majority of patients were stage 4 adenocarcinomas with good performance status treated with platinum-based chemotherapy. Stage, performance status, CRP, Albumin, LDH and WBC retained independent prognostic value and were used to create the MPS. The MPS predicted 3 well defined risk groups of patients with the following median survival and (95% CI) in months: high risk group (87 patients), 5.0 (4.2—7.0); intermediary risk group (98 patients), 9.6 (8.4—11.9); and low risk group (84 patients) 15.2 (12.4—25.1). When the MPS is applied to CC, the results were replicated for each risk group. Overall the TC had a C-stats of 0.673 (95% CI: 0.668, 0.679) while the CC of 0.702 (95% CI: 0.696, 0.708). Conclusions: We have developed a Montreal Prognostic Score based on stage, performance status and the baseline value of CRP, Albumin, LDH, WBC. This MPS has a high capacity of discriminating survival and might have wide implications in clinical practice and research.

In this issue of Critical Care, Cecconi and colleagues report the findings of a small trial of goal-directed hemodynamic therapy (GDT) in patients undergoing major orthopedic surgery under regional anesthesia. This is an interesting trial and the first of which we are aware to test the efficacy of GDT in this patient group. The findings suggest that this intervention is associated with improved adverse event rates after surgery. However, in this trial, as in all small trials of GDT, the potential for bias leaves some uncertainty regarding how widely the findings should be implemented. Such limitations may be impossible to completely eliminate from trials of complex interventions, but large multicenter trials may allow us to substantially decrease bias and improve the generalizability of the findings.

In 1988 the deans of 12 (out of 16) Canadian medical schools appointed representatives to a Canadian Palliative Care Curriculum Committee. The Committee has subsequently published the Canadian Palliative Care Curriculum which outlines specific goals and objectives for palliative care instruction in undergraduate medical teaching. The Curriculum covers 22 different topics, including 13 symptoms and 9 psychosocial issues. The Canadian Curriculum Committee continues to meet and is now considering other national educational initiatives in palliative care.

Notwithstanding our best efforts, the incidence and mortality of cancer continue to rise in both the developed and developing worlds. Military terminology is sometimes used to denote the energy and drive inherent in our cancer programmes. We often talk of cancer in terms of a war. In the optimistic 1960s and 1970s we may have thought that our war would be a blitzkrieg war. Unfortunately, the war against cancer to the present time is more reminiscent of the trench warfare of World War I. Similar to trench war in 1916, small advances such as Marshal Haig achieved at the Somme, are sometimes assigned far more significance than is deserved. Is this situation going to change over the next 10 years? Reviewing the mortality projections of the whole population registry in Alberta, I do not anticipate that, at least in our province, mortality figures for the common adenocarcinomas and squamous cell carcinomas which afflict adults are likely to drop. There is reason for optimism that the fruits of cancer research in the 1990s will impact on these projections. However, the advances that are currently touted in the laboratory must work their way through clinical trials and over an increasing number of administrative-legal hurdles to reach the bedside. It is likely that, in the best of situations, the effects of these new approaches will not be noted for a number of years. There are four components of a national cancer control programme

Regulatory T cells (Tregs) are a specialized subset of T cells that play a key role in immune regulation. Harnessing the suppressive function of Tregs is a major area of interest as they hold great potential for the treatment of autoimmune disorders. The first step towards quality Treg research is the isolation of highly purified, functional Tregs. With unique cell isolation platforms, STEMCELL has developed a full range of products for the rapid and efficient isolation of highly functional Tregs from virtually any peripheral blood sample. RosetteSep is an antibody mediated buoyant density centrifugation method used to isolate unlabelled cells specifically from whole blood or buffy coat samples. EasySep is an immunomagnetic cell separation method used to isolate cells from fresh or previously frozen PBMCs. Treg pre-enrichment is achieved by antibody mediated crosslinking of unwanted cells to either red blood cells (RosetteSep) or magnetic particles (EasySep) allowing their removal by Ficoll centrifugation or magnetic separation, respectively. RosetteSep or EasySep pre-enriched Treg populations consist of CD4+, CD4+CD127low or CD4+CD127lowCD49d- T cells. Pre-enriched Tregs can be further purified using EasySep positive selection to isolate Tregs expressing high levels of cell surface CD25. Purities of 85% +/- 10% CD4+CD25highFOXP3+ human Tregs can be achieved depending on the Treg population. From start to finish, Treg isolations can be completed in less than 3 hours.

A system for transmitting a compressed video signal over a radio link has been developed. The scheme involves altering the output bitstream of an H.261 videocodec to allow data transmission over a Digital European Cordless Telecommunications (DECT) demonstrator system. The system was used to demonstrate acceptable picture quality at bit rates between 32 kbit/s and 284 kbit/s. The high error rate possible for a radio link requires that techniques for improving the error resilience of the coding scheme be investigated. The resilience may be improved by forward error correction, interleaving of the data stream and by repeating blocks which have been corrupted by transmission. The viability of the system has been proven by hardware trials but further study is required before the system is usable on a real network.© (1992) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Cholera epidemics, mass unemployment, drug trafficking, and conflict: these are the signs of Andean societies in crisis. Whole communities are now on the margins of survival in Bolivia, Chile, Colombia, Ecuador, and Peru. Daunting levels of poverty have been created by harsh new economic policies, which compound the legacy of colonial exploitation, military dictatorship, unfair terms of international trade, and the heavy burden of foreign debt.

e22063 Background: Over the past decade, dozens of studies have shown that metformin not only decreases mortality in diabetics, it also significantly reduces CRP and reduces the risks of cancer in rodent and human cell lines. We report on the survival of lung cancer patients concomitantly exposed to metformin in our community-based program. Methods: 850 patients undergoing treatment from a prospectively collected pulmonary oncology database of the SMBD-Jewish General Hospital over an 8-year period were analyzed. Pilot observational study of survival was performed using Cox regression model. The factors that were included in the model were age, gender, stage, histology and metformin use. Results: 850 patients (F: M=375:475; mean age of 66) were diagnosed since 2000 and followed in pulmonary oncology outpatient clinic for NSCLC. 523 (62%) of those patients were diagnosed with adenocarcinoma; 488 (57%) were stage IIIB with pleural effusion/IV. 79(9%) patients were receiving treatment with metformin for their comorbid type 2 diabetes. The Cox regression analysis demonstrated that age, gender, stage and use of metformin were significant prognostic factors for survival. The use of metformin is associated with a 37% (HR 1.37; CI 1.01–1.84) (p=0.039) increase in survival. Conclusions: Thus, the result obtained from our model suggests that use of metformin may be associated with better survival of lung cancer patients. As this is a pilot study, we will consider alternative explanations. No significant financial relationships to disclose.

e20631 Background: AVR118 represents a new class of cytoprotective drugs in managing symptoms associated with anorexia\/ cachexia. In a previous study in patients with advanced HIV-AIDS, an improvement in appetite, strength and alertness was noted. The precise mechanism of action is not understood, but activity may be related to AVR118's adenosine based components. Other active components include guanosine and branched chain amino acids leucine and valine. Objective: To determine the effect of AVR118 on appetite, early satiety and nutritional intake in patients with advanced cancer. Secondary endpoints include changes in performance status, lean muscle mass and quality of Life (QOL). Methods: Eligible adult patients received 4.0 ml of AVR118 subcutaneous daily injections. Patients underwent bi-monthly evaluations during the 28 day initial treatment (phase A) Evaluations included Karnofsky performance status, Edmonton Symptoms Assessment Scale (ESAS), Patient Generated Subjective Global Assessment (PG-SGA), Simmonds Functional Assessment, Dyspepsia Symptom Severity Index, Weight, Lean Body Mass, skin fold thickness and grip strength. Patients who benefited from phase A could elect to continue with therapy (phase B). Results: Currently, of 16 enrolled patients 7 have completed phase A. All 7 patients chose to continue with AVR118 treatment (phase B). Improvements in anorexia and PG-SGA scores were seen in 7/7 and 6/7 patients respectively. Weight stabilization or gain was observed in 5/7 patients. All other parameters showed no significant difference. There was AVR118 has been well tolerated and no serious side effects have been reported. Conclusions: Based on these positive results, the primary endpoints have been achieved and the study will be expanded from 14 to 30 patients. [Table: see text]

8092 Background: Chronic systemic inflammation is a well recognized strong adverse prognostic factor in advanced NSCLC. We have previously identified that in stage IIIB/IV NSCLC the presence of elevated C-reactive protein is associated with early progression of the disease and reduction in median survival. Little is known, however, about CRP behavior over time and its correlation with response to chemotherapy and survival. Methods: Newly diagnosed NSCLC with IIIB/IV disease had CRP measured prior to 1st treatment and after 2 cycles of chemotherapy between February 2005 and September 2008. For each measure CRP level was categorized as < 10mg/L or ≥10mg/L. Response was evaluated by chest CT following two cycles of CTX and rated as progression (PD) or freedom from progression (FFP). We investigated the association between change in CRP and response to 2 cycles of CTX, as well as survival. Results: 143 pts were enrolled. Of those, 62 patients had a CRP level [Table: see text] No significant financial relationships to disclose.

In a prospective open study we tested the Edmonton injector (EI), a device designed by our group for subcutaneous injection of narcotics. In 25 patients, the EI was used for patient-controlled analgesia (PCA); mean duration of treatment was 28 +/- 10 days. Mean equivalent daily dose of morphine was 160 +/- 85 mg. All patients found the EI safe and simple to operate. The main reason for discontinuation was death (10 cases) or return to oral narcotics (8 cases). In 20 patients who were admitted to the hospital and were too ill to learn PCA, the EI was used for regular s.c. administration by nurses. Narcotics were administered every 4 h and extra doses were administered on a 'PRN' basis. Waiting time for a 'PRN' dose in 8 patients before starting the EI was 18 +/- 7 min; after the EI was started, it was 3 +/- 4 min (P less than 0.01). We conclude that the EI is safe, effective and inexpensive, and that it will be particularly useful in smaller hospitals and developing countries.

9594 Background: Cancer cachexia trials are plagued by high drop out rates lessening the impact of such studies. We hypothesized that patients with a cancer-related chronic inflammatory state (CIS)...

9567 Background: Weight loss and malnutrition are common in patients with non-small cell lung cancer (NSCLC) and have a negative impact on survival. Early detection and intervention may impact posi...

8102 Background: An elevated baseline C-reactive protein (CRP) is a significant marker presaging shortened patient survival in non small lung cancer (NSCLC) and other tumors. The reason for this as...

We report an open, uncontrolled study designed to assess the effects of subcutaneous (SC) morphine on dyspnea of terminal cancer. Twenty patients with dyspnea caused by restrictive respiratory failure received an SC dose of morphine of 5 mg (5 patients who were not receiving narcotics), or equivalent to 2.5 times their regular dose (15 patients who were receiving narcotics for pain). Dyspnea (D) and pain (15 cases) were measured before the dose and every 15 min for 150 min after the injection using a visual analog scale 0-100. Respiratory rate (RR), respiratory effort (RE) (score 1-6), arterial saturation of O2 (SO2) and end-tidal PACO2 were determined before and 45 min after SC morphine. D, RR, RE, SO2, and PACO2 were 68 +/- 32, 32 +/- 7; 3.5 +/- 1.8, 87 +/- 10, and 31 +/- 12, respectively, before SC morphine, and 34 +/- 25 (P less than 0.001), 31 +/- 9 (P:NS), 3.2 +/- 1.9 (P:NS), 86 +/- 11 (P:NS), and 33 +/- 9 (P:NS), respectively, 45 min after SC morphine. Nineteen of 20 patients (95%) reported improved dyspnea after morphine. We conclude that morphine appears to improve dyspnea without causing a significant deterioration in respiratory function in terminal cancer patients. Double-blind placebo controlled studies are needed in this population.

This double-blind, cross-over trial was designed to assess the effects of megestrol acetate (MA) on cancer-induced cachexia. Forty consecutive malnourished patients with advanced non-hormone-responsive tumors receiving no antineoplastic treatment were randomized to receive MA 480 mg/day versus placebo for 7 days. During day 8, a cross-over was made until day 15. Appetite, pain, nausea, depression, energy, and well-being were assessed with a visual analog scale (0 to 100 mm) at 9:00 AM and 4:00 PM during days 6, 7, 13, and 14. Weight (W;kg), tricep skinfold (TS; mm), arm circumference (AC; cm), and calf circumference (CC; cm) were measured at days 1, 8, and 15. Caloric intake (CI; Kcal/day) was determined during days 6, 7, 13, and 14. In 31 evaluable patients, the percentual difference in appetite at 9:00 AM, appetite at 4:00 PM, energy, and well-being after MA was +15.1, +14, +3.2, and +5.2, versus -12 (P = 0.03), -5.1 (P = 0.015), -10 (P = 0.024), and -8.3 (not significant) after placebo. Percentual difference in W, TS, AC, and CC after MA was +0.2, +1, -0.1, and +0.4 versus -0.8 (P = 0.03), -0.8 (P = 0.001), -0.3 (not significant), and -0.5 (P = 0.04) after placebo. CI during MA was 3480 +/- 1574 (48-hour intake), versus 2793 +/- 1542 (P less than 0.001) during placebo. Patients and investigators blindly chose MA in 20 (66%, P = 0.023) and 28 cases (92%, P less than 0.001), placebo in eight and two cases, and made no choice in three and one cases, respectively. Toxicity consisted of mild edema and nausea in three and two cases, respectively. After mean follow-up of 27 +/- 13 days, on an open basis, an average increase in W and AC of 4.8 +/- 1.7 kg and 2.8 +/- 1.7 cm was observed, respectively. The authors conclude that MA is a powerful appetite stimulant with subjective and objective effects on nutritional status.