An interdisciplinary palliative rehabilitation intervention bolstering general self-efficacy to attenuate symptoms of depression in patients living with advanced cancer.

PURPOSE: Patients with advanced cancer, post-anticancer treatment, are living longer than 10-20 years ago. This emerging population of survivors has unique palliative and rehabilitation needs. A particular concern is depression, which can impair functioning, quality of life, and survival. The interdisciplinary Palliative Rehabilitation Program offers holistic palliative rehabilitation for this population using a self-efficacy framework. The current study examined the unique impact of three program factors that have been shown to improve depression: inflammation, exercise, and self-efficacy. METHOD: Patients underwent a 2-month interdisciplinary intervention (up to six disciplines) and thorough pre-post assessments. Measures included serum C-reactive protein, 6-min walk test, General Self-efficacy Scale, and Hospital Anxiety and Depression Scale (depression subscale). Paired t tests analyzed pre-post changes in each variable, and a hierarchical linear regression analyzed the predictors' unique contributions of changes in depression in this quasi-experimental design. RESULTS: The sample included 80 patients (52.5% females), with stages 3/4 heterogeneous cancers. Results revealed that C-reactive protein (CRP) did not significantly change pre-post, from 7.39 (SD = 11.99) to 9.47 mg/L (SD = 16.41), p = 0.110, exercise significantly increased, from 372.55 (SD = 137.71) to 412.64 m (SD = 144.31), p < 0.001, self-efficacy significantly increased from 27.86 (SD = 6.16) to 31.23 units (SD = 5.77), p < 0.001, and depression scores significantly decreased, from 7.14 (SD = 3.91) to 5.95 units (SD = 3.51), p = 0.002. A hierarchical linear regression revealed that this model explained 15% of variance in changes in depression scores, p = 0.006. Change in self-efficacy accounted for 11% of change in depression scores (p < 0.001). Change in CRP and exercise did not make a significant contribution. CONCLUSIONS: A self-efficacy framework may be a helpful ingredient in interdisciplinary intervention to decrease depressive symptomatology.

Erratum: Tumour inflammatory response: adding fuel to the fire?

[This corrects the article on p. 7 in vol. 22, PMID: 25684982.].

An interprofessional palliative care oncology rehabilitation program: effects on function and predictors of program completion.

BACKGROUND: After treatment, patients with active cancer face a considerable burden from the effects of both the disease and its treatment. The Palliative Rehabilitation Program (prp) is designed to ameliorate disease effects and to improve the patient's functioning. The present study evaluated predictors of program completion and changes in functioning, symptoms, and well-being after the program. METHODS: The program received referrals for 173 patients who had finished anticancer therapy. Of those 173 patients, 116 with advanced cancer were eligible and enrolled in the 8-week interprofessional prp; 67 completed it. Measures of physical, nutritional, social, and psychological functioning were evaluated at entry to the program and at completion. RESULTS: Participants experienced significant improvements in physical performance (p < 0.000), nutrition (p = 0.001), symptom severity (p = 0.005 to 0.001), symptom interference with functioning (p = 0.003 to 0.001), fatigue (p = 0.001), and physical endurance, mobility, and balance or function (p = 0.001 to 0.001). Reasons that participants did not complete the prp were disease progression, geographic inaccessibility, being too well (program not challenging enough), death, and personal or unknown reasons. A normal level of C-reactive protein (<10 mg/L, p = 0.029) was a predictor of program completion. CONCLUSIONS: Patients living with advanced cancers who underwent the interprofessional prp experienced significant improvement in functioning across several domains. Program completion can be predicted by a normal level of C-reactive protein.

The association between malnutrition and psychological distress in patients with advanced head-and-neck cancer.

OBJECTIVE: Malnutrition and psychological distress are often seen in patients with head-and-neck cancer, but little is known about the interrelationships between those two symptoms. The present study examined the relationship between malnutrition and psychological distress in patients with advanced head-and-neck cancer. METHODS: Using the Patient-Generated Subjective Global Assessment, 99 patients with advanced-stage head-and-neck cancer were screened for nutrition status. The patients were also screened for psychosocial distress (using the Distress Thermometer) and for psychosocial issues (using the Problem Checklist). Any relationship between malnutrition and psychosocial distress was determined by regression and correlation analysis. We also used t-tests to compare distress levels for patients with and without specific nutrition-related symptoms. RESULTS: The study group included 80 men and 19 women [mean age: 58.4 ± 10.9 years (range: 23-85 years)]. The correlation between poorer nutrition status and level of psychological distress was significant r = 0.37 (p < 0.001). Specifically, reduced food intake and symptoms were both positively associated with distress: r = 0.27 and r = 0.29 respectively, both significant at p < 0.01. After controlling for the effects of psychosocial problems and pain, nutrition status remained a significant predictor of distress, explaining 3.8% of the variance in the distress scores of the patients (p < 0.05). CONCLUSIONS: Malnutrition and symptoms were strongly related to distress in patients with advanced head-and-neck cancer. Our results suggest the need for further research into the complex relationship between nutrition status and distress and into the management of both nutrition and distress in cancer care.

Cancer nutrition and rehabilitation-its time has come!

Cancer is a systemic disease that can affect nearly every organ in the body, resulting in a progressive loss of organ function. That loss of function may be initially slow, having minimal effect, or it may be rapid, resulting in more dramatic changes.The usual medical management of patients with cancer has focused more specifically on the administration of cytotoxic treatments. These treatments can potentially eradicate or minimize the tumour, but they may also have toxic side effects that in turn can also affect the patient.Cancer rehabilitation is a process that assists the individual with a cancer diagnosis to obtain optimal physical, social, psychological, and vocational functioning within the limits created by the disease and its treatment. The McGill Cancer Nutrition and Rehabilitation (CNR) program developed as a result of the ever-increasing demand for a focus on addressing individual cancer patients and their needs, as well as on achieving optimal tumour-related outcomes. Using an interdisciplinary approach, the CNR's global objective is to empower individuals who are experiencing loss of function, fatigue, malnutrition, psychological distress, and other symptoms as a result of cancer or its treatment to improve their own quality of life. All team members-experts in their respective fields-assess all patients. At a subsequent team discussion and planning meeting, a specific 8-week program is designed for each patient. The hoped-for outcome for the CNR program is primarily to empower patients to "take control" or to enable them to improve their own quality of life. This article reviews the philosophy of the CNR's approach and the roles played by the various members of the team.

First line therapy with paclitaxel (Taxol) and pegylated liposomal doxorubicin (Caelyx) in patients with metastatic breast cancer: a multicentre phase II study.

The aim of this multicentric phase II study was to investigate the efficacy and toxicity of a combination of chemotherapy containing paclitaxel (Taxol) and a novel compound, a liposomal encapsulated doxorubicin (Caelyx), as first line therapy for patients with metastatic breast cancer. Thirty-four patients with advanced breast cancer were treated with a combination of paclitaxel 175 mg/m2 and liposomal doxorubicin 30 mg/m2, every 3 weeks. The combination chemotherapy was effective in 73% of the patients (ITT) (95% CI 55-86%) (7 complete and 18 partial responses). Grade 3/4 toxicities were documented in a small number of patients. Two toxic deaths (6%) were documented, one a hepatorenal failure and another a febrile neutropenia. One patient experienced pulmonary embolism but continued on treatment after appropriate therapy. The combination of paclitaxel and liposomal encapsulated doxorubicin induces a high and durable response rate with a moderate toxicity profile.

Phase II clinical trial of carboplatin and docetaxel in patients with metastatic ovarian cancer: active combination with low incidence of peripheral neuropathy.

During the past 2 decades there have been chemotherapeutic advances in the management of patients with advanced epithelial ovarian cancer. Nevertheless, new drug combinations aimed at increasing response and survival and decreasing toxicities are under investigation. The aim of this phase II study is to determine the feasibility, efficacy and toxicity of docetaxel at a dose of 75 mg/m2 in combination with Carboplatin at an area under the curve (AUC) of 6, as first line treatment in patients with advanced ovarian cancer. 37 patients with stage III-IV epithelial ovarian cancer were entered, and are currently evaluable for response and toxicity. Treatment was well tolerated. The most common grade III and IV toxicities were leukopenia and neutropenia. The incidence of febrile neutropenia was 16.2%. Grade II and III sensory peripheral neuropathy occurred in 8.1% of patients. Peripheral neuropathy resolved in two patients and persisted for more than 10 months in one patient. An overall clinical response of 89% was documented (95% CI 74.5% to 96.9%). Carboplatin and docetaxel administered according to our protocol is an effective alternative to other existing platinum-taxane based combinations. This treatment is associated with low incidence of sensory peripheral neuropathy, which is generally associated with better patient compliance and quality of life.

Malignant pleural mesothelioma: a phase II trial with docetaxel.

Current cytotoxic therapy has been of limited benefit to patients with malignant pleural mesothelioma. Single agent chemotherapy has been extensively evaluated in small series of phase II clinical trials, with disappointing responses. Docetaxel, an effective taxane in the treatment of advanced breast cancer and non-small-cell lung cancer, was administered intravenously at a dose of 100 mg/m2 every 3 weeks to 30 chemotherapy naive patients with malignant pleural mesothelioma in a prospective multi-institutional phase II clinical trial. An objective response rate (partial responses) of 10% was documented. Additionally, 21% of the patients had minor responses (intention-to-treat analysis). Three patients died within 2 weeks post-first cycle of therapy, although only one patient's death was directly attributed to the investigational drug, whilst in the majority of the patients, manageable and treatable toxicities were encountered. In this phase II clinical trial, docetaxel proved to be mildly effective in the treatment of patients with malignant pleural mesothelioma.

A prospective randomized study of alpha-2b interferon plus hydroxyurea or cytarabine for patients with early chronic phase chronic myelogenous leukemia: the International Oncology Study Group CML1 study.

A prospective randomized international study of 143 patients showed no apparent early survival advantage conferred by combining cytarabine, rather than hydroxyurea, with INF as first-line CML therapy. Combinations of alpha-interferon (INF) and chemotherapeutic agents are currently first-line therapy for the majority of patients with chronic myeloid leukemia (CML). The International Oncology Study Group conducted a prospective randomized study comparing INF combined with hydroxyurea or cytarabine. The primary study aim was to compare the survival durations in these patient cohorts. Patients with early chronic phase CML were randomized to receive INF 5 million units (Mu) given five times per week subcutaneously plus hydroxyurea or cytarabine as required to achieve a complete hematologic response and to maintain a WBC count between 2x10(9)/L and 10x10(9)/L and a platelet count between 75x10(9)/L and 100x10(9)/L. Therapy continued as tolerated unless progressive or blast phase disease occurred. At 36 months, the actuarial survival rate was equivalent in both groups: HI group (79 patients) survival was 85% (95% CI, 68-100%), as compared to 95% (95% CI, 79-100%) in the CI group (64 patients). In conclusion if seems that there is no apparent early survival advantage conferred by combining cytarabine, rather than hydroxyurea, with INF as first-line CML therapy.

The chemosensitizing potential of GF120918 is independent of the magnitude of P-glycoprotein-mediated resistance to conventional chemotherapeutic agents in a small cell lung cancer line.

GF120918, at 250 ng/ml, increased the sensitivity of a P-glycoprotein (P-gp)-mediated multidrug resistant (MDR) small cell lung cancer cell line (H69/LX4) to the P-gp substrates, paclitaxel, taxotere, vinblastine, vinorelbine, daunorubicin and etoposide to levels which were either greater (in the case of etoposide) or close to that of the parent cell line (H69/P). This was achieved in spite of the great variation in the levels of resistance of the MDR cell line for the various anti-cancer drugs tested. These data suggest that GF120918 is a potent antagonist of P-gp mediated multidrug resistance, even in the case of high levels of resistance, as was the case with paclitaxel and taxotere (2560 and 2215 fold more than the sensitive parent cell line respectively).

A phase II study of oral clofazimine in unresectable and metastatic hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma is highly refractory to most chemotherapeutic agents. Clofazimine, a riminophenazine compound used to treat leprosy since 1962, inhibits various cancer cell lines, including hepatocellular carcinoma cell lines, via phospholipase A2 dependant processes. Clofazimine also inhibits p170-glycoprotein, the mdr1 gene product. PATIENTS AND METHODS: Thirty patients (26 males and four females) with unresectable (25) or metastatic (5) hepatocellular carcinoma received oral clofazimine 600 mg daily for two weeks, followed by 400 mg daily until progression or death. RESULTS: There were three responses (10%)--one of a soft tissue metastasis, and two of local disease, with 13 patients disease stabilizing for up to 20 months. The overall median survival was 13 weeks. Adverse events included hyperpigmentation, eczematous skin rashes and palpitations. CONCLUSIONS: Although only three patients had an objective response (10%), the 13 patients with stable disease for up to 20 months, and an overall median survival of 13 weeks, suggest that clofazimine, or other riminophenazine compounds may prove to be of value in hepatocellular carcinoma.

Differential expression of transforming growth factor alpha, adhesions molecules and integrins in primary, metastatic liver tumors and in liver cirrhosis.

Changes in cytokines, intercellular cell-matrix adhesion molecules and integrins may influenced tumor cell invasion and metastases. This study described the distribution, pattern and intensity of cytokine TGFa, adhesion molecules CD 34 and CD 44 and integrins a2, a3, CD 29 (beta 1 chain) and CD 61 (beta 3 chain) in hepatocellular carcinoma (HCC), metastatic liver tumors and hepatic cirrhosis. Fresh snap-frozen tissue from 20 cases of HCC, 5 metastatic adenocarcinomas and 10 cirrhotic livers was studied immunohistochemically using available antibodies. The most intense staining of TGFa was found in metastatic adenocarcinoma, following by regenerating hepatocytes in cirrhotic liver and well differentiated HCC. Insignificant differences in activity of CD 34 in various pathologies, up-regulation of CD 44 in poorly differentiated HCC and down-regulation in metastatic tumors were found. All integrins studied showed down-regulation in poorly differentiated HCC, relatively high activity of a2, a3 and beta 1 in metastatic tumors and the presence of all integrins in cirrhotic liver.

Differential expression of extracellular matrix proteins and integrins in hepatocellular carcinoma and chronic liver disease.

UNLABELLED: Extracellular matrix (ECM) molecules play an important role in the orderly development, differentiation and function of tissues. The interaction of ECM with heterodimeric transmembrane glycoproteins called integrins is thought to be an important factor in cell-cell and cell-substrate adhesions in tumours, tumour invasion and metastases. PURPOSE: To investigate ECM and adhesion molecules in hepatocellular and breast carcinomas, chronic hepatitis and hepatic cirrhosis. MATERIALS AND METHODS: Frozen in liquid nitrogen and also paraffin-embedded biopsies from hepatocellular adenomas (3), well-differentiated (53) and poorly differentiated (19) hepatocellular carcinomas, lobular (3) and poorly differentiated (7) breast carcinomas, chronic hepatitis (10) and hepatic cirrhosis (10) were collected and investigated. Immunohistochemical techniques were applied for the detection of ECM molecules fibronectin, laminin, tenascin, vitronectin and integrins alpha 5 and beta 4. RESULTS: Poorer differentiation of the tumours was characterised by up-regulation of fibronectin, tenascin and vitronectin and downregulation of laminin and both integrins. These changes were observed in the interface between tumour and invaded tissues and within cancerous sinusoids. CONCLUSION: Increased expression of some ECM glycoproteins around tumour foci suggests a role in stimulating cancer cells or a host defence mechanism accompanied by desmoplastic response to them. Downregulation of laminin in poorly differentiated tumours identifying loss of basement membrane components and parallels quantitative changes in the expression of adhesion molecules in both hepatic and breast carcinomas. This may be an important step in enhancing local invasiveness of tumour cells, facilitating tumour spreading and biological malignancy.

Ifosfamide and mesna in combination with other cytostatic drugs in the treatment of patients with advanced cancer.

Fifty patients with histologically confirmed advanced malignancies were treated with ifosfamide and mesna plus other cytostatics. The other cytostatic drugs added to the treatment regimen were cisplatin (36 pts), etoposide (31 pts) and doxorubicin (20 pts). Among previously untreated patients objective response was documented in 12 of 19 pts with ovarian cancer, 9 of 14 with small cell cancer of the lung and in all 3 pts with Ewing's sarcoma. Among patients with disease refractory to prior cytostatic treatment, objective response was documented in 8 of 9 with testicular cancer, 1 of 3 with high grade lymphoma and 0 of 2 with osteosarcoma. Side-effects due to the combination of ifosfamide plus mesna and other cytostatics were acceptable. No life-threatening or lethal toxicities occurred. Most commonly encountered toxicities were leukopenia (64%), nausea and vomiting (84%), alopecia (63%), CNS toxicity (30%) and renal toxicity (12%).