Tocilizumab in grade 4 hepatitis secondary to immune checkpoint inhibitor: a case report and review of the literature.

First- and second-line treatments for immune checkpoint inhibitor-related hepatotoxicity (IRH) are well established; however, evidence for third-line therapies is limited. We present a 68-year-old female with relapsed metastatic non-small-cell lung carcinoma despite multiple treatments. A fortnight after the second cycle of CTLA-4 inhibitor immunotherapy, she developed scleral icterus and mild jaundice with significant elevation in liver enzymes. A diagnosis of IRH was made, and despite corticosteroids, mycophenolate and tacrolimus, liver enzymes continued to worsen. One infusion of tocilizumab was given, which resulted in a remarkable improvement. Prednisolone and tacrolimus were then tapered over the ensuing months, and mycophenolate was continued. Given the rapid improvement in liver enzymes with tocilizumab, this treatment should be considered as a third-line treatment in IRH.

A lady had cancer of the lung. A new medication was started but the liver became damaged. Three medications were tried to help the liver. None of these worked. Another drug (called tocilizumab) was tried and worked. The liver got better.

Effect of anti-inflammatory diets on inflammation markers in adult human populations: a systematic review of randomized controlled trials.

CONTEXT: Chronic inflammation, characterized by prolonged elevated inflammation markers, is linked to several chronic conditions. Diet can influence the levels of inflammation markers in the body. OBJECTIVE: The aim of this systematic review was to assess the effects of anti-inflammatory diets on 14 different inflammation markers in adults. DATA SOURCES: This systematic review conducted searches using Medline, PubMed, EMCare, Cochrane, and CINAHL, to locate randomized controlled trials (RCTs). DATA EXTRACTION: Two researchers independently screened 1537 RCTs that measured changes in inflammation markers after prescription of an intervention diet. DATA ANALYSIS: In total, 20 RCTs were included and assessed qualitatively. The results demonstrated that a Mediterranean diet can bring about statistically significant and clinically meaningful between-group differences in interleukins -1α, -1ß, -4, -5, -6, -7, -8, -10, and -18, interferon γ, tumor necrosis factor α, C-reactive protein, and high-sensitivity C-reactive protein, as compared with a control diet. CONCLUSIONS: There may be a link between diet, inflammation markers, and disease outcomes in various adult populations. However, further research using consistent RCT protocols is required to determine correlations between diet, specific inflammation markers, and clinically relevant outcomes.

Phase I Trial of nab-Paclitaxel Administered Concurrently With Radiotherapy in Patients With Locally Advanced Inoperable Pancreatic Adenocarcinoma.

OBJECTIVES: Nab-paclitaxel has radiosensitizing antitumor efficacy in pancreatic cancer. We aimed to establish maximum tolerated dose (MTD) of nab-paclitaxel with radiotherapy in unresectable locally advanced pancreatic cancer. METHODS: In a phase I dose escalation trial patients received weekly nab-paclitaxel for 6 weeks with external beam radiotherapy (EBRT). 3 + 3 design was used with nab-paclitaxel doses: 25 mg/m 2 (cohort 1), 50 mg/m 2 (cohort 2), 75 mg/m 2 (cohort 3), and 100 mg/m 2 (cohort 4). Primary endpoint was MTD. Secondary objectives were progression-free survival and overall survival. RESULTS: Fourteen patients were recruited. Median age was 69 years (range, 40-86). Grade 1/2 toxicities were nausea (93%), vomiting (54%), diarrhea (57%), and fatigue (69%). There were no dose limiting toxicities (DLT) in cohorts 1 to 3. In cohort 4, DLTs of febrile neutropenia and enterocolitis were observed in patient 1. Subsequent DLT of febrile neutropenia and enterocolitis occurred in patient 5 in the expanded cohort. Following chemoradiotherapy median progression-free survival was 4.7 months (95% confidence interval, 2.5-27.5) and median overall survival was 10.8 months (95% confidence interval, 6.37-25.2). CONCLUSIONS: Nab-paclitaxel and EBRT was well-tolerated at doses below 100 mg/m 2 . The MTD and recommended phase II study dose for nab-paclitaxel with EBRT is 75 mg/m 2 in this disease.

Eosinophilic Vasculitis and Arteritic Anterior Ischemic Optic Neuropathy Associated With Anti-PD-L1 Therapy.

Immune checkpoint inhibitor therapy is frequently associated with immune-related adverse events, which occasionally manifest with visual symptoms. Here, we describe a case of unilateral and sudden-onset painless vision loss in an 82-year-old man with metastatic non-small cell lung cancer receiving immunotherapy with the anti-programmed death-ligand 1 agent atezolizumab. Examination demonstrated a right-sided relative afferent pupillary defect, diffusely swollen optic disc, and delayed choroidal and retinal arterial filling on fundus fluorescein angiography, consistent with an arteritic anterior ischemic optic neuropathy. Histology of an ipsilateral temporal artery biopsy revealed a transmural eosinophilic infiltrate without granulomas, while serology revealed the presence of antineutrophil cytoplasmic antibodies. Peripheral eosinophilia was also noted, which preceded treatment by several months. This report highlights the importance of clinician awareness of immune checkpoint inhibitors and their systemic and ophthalmic complications, which rarely appear to extend to eosinophilic temporal arteritis.

Real-world experience of nivolumab in the treatment of poor performance status patients with advanced non-small cell lung cancer.

BACKGROUND: Nivolumab improves disease control and survival in advanced NSCLC in patients with good performance status (PS), but there is limited data on its efficacy in patients with poor PS. AIM: Primary objective of the study was to evaluate the efficacy and safety of nivolumab and examine the influence of PS on outcomes. METHODS AND RESULTS: Retrospective analysis of patients treated with single-agent nivolumab for advanced NSCLC at a single institution was performed. Sixty-six patients treated with nivolumab were identified (33 male) with a median age of 68.5 years. Fifty-six (85%) patients were current or former smokers and 17 (26%) had brain metastasis. All patients had received prior chemotherapy, 39 (59%) patients received one and 27 (41%) had ≥2 prior lines of therapy. Median overall survival (OS) was 7.1 months (95%CI 3.61-11.3) in the overall study population. OS of patients with PS ≥2 at the start of treatment was 3.04 months (95%CI 1.64-7.36) as compared to 10.23 months (95%CI 7.06-18.9) with PS ≤1. The overall response rate was 7% (four patients had a partial response), 23 (40%) patients had stable disease; the overall disease control rate (partial response and stable disease) was 47%. Twenty-six (40%) patients had PS ≥2 at the start of treatment and 2 (8%) of these patients developed a partial response, 4 (15%) had stable disease; the overall disease control rate was 23%. Fourteen (58%) patients with PS ≥2 had disease progression at the time of first disease response evaluation. In the overall population, 20% of patients experienced grade ≥3 treatment-related adverse events (TRAEs), most commonly pneumonitis, hepatitis, and colitis. Fourteen TRAEs led to treatment discontinuation, 9 (23%) adverse events (AEs) in patients with PS ≤1 and 5 (19%) with PS ≥2. Fourteen (21%) patients died within 30 days of the last nivolumab treatment. CONCLUSION: There was no significant difference in toxicity leading to treatment discontinuation between the poor and good PS groups, but survival was shorter with poorer PS. PS appears to be an important prognostic factor and remains a relevant discriminator in the selection of treatment with immunotherapy for lung cancer.

Validation of a Short Food Frequency Questionnaire to Measure Dietary Intake of a Selection of Micronutrients in Oncology Patients Undergoing Systemic Therapy.

Dietary intake, specifically consumption of anti-inflammatory micronutrients, can play a role in both cancer initiation as well as the treatment-related outcomes experienced by patients receiving systemic cancer therapy. Increasing research is being conducted to determine whether micronutrient supplementation can aid in altering the tumor microenvironment (TME), reducing inflammatory side effects and immune-related adverse events (irAEs). However, further research pertaining to the adequacy of dietary micronutrient intake is indicated in the oncology cohort. Currently, no tool measuring dietary intakes of various micronutrients exists in the oncology population. In this study, a 21-item food frequency questionnaire (FFQ) measuring intakes of 14 different micronutrients was validated using diet history as the reference method in 112 oncology patients. Bland Altman plot and Passing Bablok regression analysis were conducted to determine agreement between the two methods. The results showed adequate agreement between FFQ and diet history for 12 nutrients including copper, iron, vitamins A, E, and D, alpha linolenic acid (ALA), long-chain omega 3 fatty acids (LC n3-FA), arginine, glutamic acid, isoleucine, leucine, and valine. This 21-item FFQ, which takes an average of 10 min to complete, can be utilized as a quick screening tool to determine adequacy for 12 different micronutrients in place of a diet history.

Predicting chemotherapy-induced menopause using baseline and post-chemotherapy anti-Müllerian hormone levels: Results of a pilot study.

BACKGROUND: Chemotherapy can cause premature menopause which may result in adverse effects such as fertility loss, osteoporosis, cardiovascular disease and menopausal symptoms. It is thus very important that women are provided with accurate information regarding their risk of premature menopause as a consequence of proposed chemotherapy. Unfortunately, at present there are no reliable tools which can be applied in clinical practice to estimate the risk of premature menopause in women undergoing chemotherapy, beyond age of the patient and form of chemotherapy utilized. AIM: This was a pilot study to determine whether AMH levels pre and during chemotherapy are able to predict for chemotherapy induced menopause, and to assess quality of life and menopausal symptoms. METHODS AND RESULTS: Premenopausal women between 18 to 45 who were planned to undergo gonadotoxic chemotherapy with curative intent for either breast cancer or haematologic malignancy were recruited from a single centre. AMH, FSH, LH and oestradiol levels were recorded prior to commencement of therapy, during and following completion of chemotherapy. Menstrual status, menopausal symptoms and quality of life data were collected at baseline and during follow-up. Twenty two women were recruited. The baseline AMH was higher in women who regained menses post-chemotherapy (median 23.1 vs 9.9 pM (P = .06). Menopausal symptoms were significantly higher at 1 year post diagnosis than at baseline however quality of life was similar. CONCLUSION: AMH may be useful for predicting chemotherapy induced menopause. Further research is still required to determine the place of such testing for patient counselling and management.

Nivolumab-induced synovitis is characterized by florid T cell infiltration and rapid resolution with synovial biopsy-guided therapy.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are associated with rheumatic and musculoskeletal immune-related adverse events (irAEs) in 5%-20% of patients. Currently, patients refractory to corticosteroids and conventional disease-modifying antirheumatic drugs (cDMARD) are treated with biological DMARDs (bDMARDs) targeting tumor necrosis factor α (TNFα) and interleukin-6, although without a clear biological rationale. Synovial tissue (ST) biopsy presents a valuable opportunity to investigate irAE pathogenesis and appropriately stratify bDMARD use in refractory irAE patients. CASE PRESENTATION: We provide the first report of comparative, parallel ST and synovial fluid (SF) analyses of severe, cDMARD-refractory, seronegative polyarthritis, classified as a grade 3 irAE occurring in response to nivolumab treatment for metastatic squamous cell lung cancer, in comparison with ST and SF from patients with untreated rheumatoid arthritis (RA). We investigated immunohistochemical labeling of ST cytokine expression as a biological rationale for selecting therapy. Flow cytometric analysis of lymphocytes from ST, SF and blood collected before and after synovial biopsy-guided therapy, in comparison with RA, were evaluated for insights into the immunopathogenesis of irAE. Immunolabeling of ST demonstrated an excess of TNFα cytokine expression. Subsequent treatment with infliximab resulted in resolution of inflammatory symptoms and a significant reduction in C reactive protein levels. Flow cytometric analysis of synovial infiltrates indicated absence of programmed cell death protein-1 (PD-1) receptor positivity despite cessation of nivolumab approximately 200 days prior to the analyzes. CONCLUSIONS: A deeper understanding of the immunopathogenetic basis of immune activation in irAEs is required in order to select therapy that is likely to be the most effective. This is the first report investigating parallel blood, ST and SF in ICI-induced severe rheumatic irAE. Use of a bDMARD directed by the dominant inflammatory cytokine achieved resolution of synovitis while maintaining cancer remission.

Survival and late toxicities following concurrent chemo-radiotherapy for locally advanced stage III non-small cell lung cancer: findings of a 10-year Australian single centre experience with long term clinical follow up.

BACKGROUND: The preferred management of patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC) is concurrent chemo-radiotherapy (CRT). Acute CRT-related toxicities are well defined, however, less is known about late toxicities. The aim of the study was to examine the outcomes and late toxicities in Stage III NSCLC treated with CRT. METHODS: A retrospective review of the data from patients with stage III NSCLC treated with CRT was performed between May 2000 and June 2010. Demographics, tumour and treatment characteristics, toxicities and survival data were examined from hospital records of the patients. Progression free survival (PFS) and overall survival (OS) were evaluated by standard Kaplan-Meier survival curves. The censor date was set on 31 October 2016. RESULTS: Sixty-three patients were identified with a median age of 66.6 years [interquartile range (IQR) 57.2-72.1], two-third (n=41, 65.1%) were male, majority were current or ex-smokers (n=52, 82.5%), 42 (66.7%) patients had stage IIIB disease and 21 (33.3%) had stage IIIA disease. The most common histologic subtype was adenocarcinoma 30 (47.6%). The median PFS and OS of the whole population was 10.6 months (95% CI, 4.1-17.3 months) and 21 months (95% CI, 12.7-29.3 months) respectively. The 5-year OS rates for stage IIIA and IIIB were 24% and 16% respectively. The 1-, 3- and 5-year OS rates for all patients were 63.5%, 46% and 18.7% respectively. Acute grade 3 and 4 toxicities included 28 haematological and 17 non-haematological events. The incidence of late toxicities was 58.9%. Thirty-three events of late grade 3 and 4 toxicities were recorded. The most common late toxicity was symptomatic radiation-induced pulmonary fibrosis (39.3%), others include ototoxicity (7.1%), persistent dysphagia (7.1%) and one case of acute myeloid leukaemia. All patients that were alive at the censor date had developed radiation-induced fibrosis with associated symptoms of respiratory insufficiency. CONCLUSIONS: The 5-year OS of patients with stage III NSCLC treated with CRT was in keeping with survival figures reported from prospective clinical trials. There is, however, significant morbidity associated with long-term survival and this should be taken into account when making informed treatment decisions.

Internet use and preferences among women living with advanced breast cancer.

Despite high distress and unmet informational and psychosocial needs, and recommendations for development of advanced breast cancer (ABC)-specific resources, there remains a paucity of appropriate, accessible psychological interventions. This survey study examined internet use and preferences of women with ABC, to gauge feasibility of providing an ABC-specific internet intervention. Most participants (83%) used the internet daily. Results indicated most women with ABC would find an ABC-specific internet intervention helpful, and that it would address gaps in current internet resources, including provision of strategies to manage treatment side-effects and fear of cancer progression.

Patterns of care in Jehovah's Witnesses patients with solid tumours and lymphoma.

BACKGROUND: Supportive care of Jehovah's Witnesses (JWs) diagnosed with cancer can be challenging, as they do not accept red blood cell (RBC) transfusions. AIM: The study was designed to determine treatment preferences and pattern of care offered to JWs diagnosed with cancer and its impact on cancer management. METHODS AND RESULTS: A retrospective cohort study of JWs with solid malignancies or lymphoma in our institution between 2005 and 2015 was conducted. Survival statistics were estimated using Kaplan Meier survival curves and Cox proportional regression model. A total of 63 JWs were identified with a median age of 70 years. At diagnosis, 34% (n = 22) had anaemia. All 63 declined RBC transfusion, including 19 patients who later developed transfusion threshold during anti-cancer treatment. Forty-three percent (n = 27) JWs had advanced (stage 4) disease, and 76% (n = 48) had Eastern Cooperative Oncology Group of 0 to 1. JWs were willing to accept surgery and radiation rather than chemotherapy. Treatment was deemed to be suboptimal in 22% (n = 14) JWs due to early treatment discontinuation, administration of non-standard chemotherapy regimen, or dose reduction due to anaemia and denial of blood transfusion. Twenty-seven percent (n = 17) received hematopoietic growth factors (erythropoiesis-stimulating agents and pegfilgrastim). There was no mortality directly attributed to anaemia or refusal of blood transfusion in the entire cohort. CONCLUSION: Jehovah's Witnesses declined RBC transfusion at diagnosis and during cancer therapy even if medically indicated. Management pathways need to be prospectively defined for this group of patients.

Online information and support needs of women with advanced breast cancer: a qualitative analysis.

PURPOSE: Women with advanced breast cancer (ABC) face significant adjustment challenges, yet few resources provide them with information and support, and attendance barriers can preclude access to face-to-face psychosocial support. This paper reports on two qualitative studies examining (i) whether information and support-seeking preferences of women with ABC could be addressed in an online intervention, and (ii) how an existing intervention for patients with early stage cancer could be adapted for women with ABC. METHODS: Women with ABC participated in telephone interviews about their information and support-seeking preferences (N = 21) and evaluated an online intervention focused on early-stage cancer (N = 15). Interviews were transcribed and underwent thematic analysis using the framework method to identify salient themes. RESULTS: Participants most commonly sought medical, lifestyle-related, and practical information/support; however, when presented with an online intervention, participants most commonly gave positive feedback on content on coping with emotional distress. Difficulty finding information and barriers to using common sources of information/support including health professionals, family and friends, and peers were reported; however, some women also reported not wanting information or support. All participants evaluating the existing intervention gave positive feedback on various components, with results suggesting an online intervention could be an effective means of providing information/support to women with ABC, given improved specificity/relevance to ABC and increased tailoring to individual circumstances and preferences. CONCLUSIONS: Adaptation of an existing online intervention for early stage cancer appears to be a promising avenue to address the information and support needs of women with ABC.

Pre-treatment serum lactate dehydrogenase as a biomarker in small cell lung cancer.

BACKGROUND: Small cell lung cancer is a rapidly progressive disease with high fatality. No sensitive and specific biomarker to assist in managing this disease exists currently. AIM: Role of pretreatment serum lactate dehydrogenase as a biomarker in small cell lung cancer. METHODS: A hospital-based cancer registry was used to identify eligible patients from 1999 to 2009. Demographic data, lactate dehydrogenase level and clinical outcome of patients were collected for analysis. RESULTS: One hundred and sixty-eight patients were identified: 61% (n = 103) males and 39% (n = 65) females. Majority had extensive stage (67%). High lactate dehydrogenase (≥230 U/L) was present in 60.4% (n = 75); mean reading 260 U/L (range 148-898 U/L) in limited stage and 470 U/L (range 116-5462 U/L) in extensive stage. Extensive stage patients with high lactate dehydrogenase had lower treatment response rate compared to those with normal lactate dehydrogenase (39% vs 79%, P = 0.002); no difference in treatment response was seen among patients with limited stage. High lactate dehydrogenase conferred a worse survival; mean overall survivals in limited and extensive stage were 8.0 and 5.2 months, respectively, in patients with elevated lactate dehydrogenase. Those with normal lactate dehydrogenase had an overall survival of 16.5 and 8.2 months, respectively. The association remained significant after adjustment for age, sex and treatment (HR 1.8, 95% CI 1.16-2.80, P = 0.009). CONCLUSION: High pretreatment lactate dehydrogenase is a prognostic marker of survival in both stages of small cell lung cancer. It is also a predictive marker of response to therapy in extensive stage. Larger prospective studies to validate our findings would be beneficial.

A Pilot Study of Self-Management-based Nutrition and Physical Activity Intervention in Cancer Survivors.

Exercise and a healthy diet are beneficial after cancer, but are not uniformly adopted by cancer survivors. This study reports on the feasibility, acceptability, and effectiveness of a self-management-based nutrition and exercise intervention for Australian cancer survivors. Adult survivors (n  =  25) during curative chemotherapy (stratum 1[S1]; n  =  11) or post-treatment (stratum 2 [S2]; n  =  14) were recruited prospectively from a single center. The Flinders Living Well Self-Management Program™ (FLW Program) was utilized to establish patient-led nutrition and exercise goals and develop a tailored 12-wk intervention plan. Fortnightly reviews occurred with assessments at baseline, 6 and 12 wk. A recruitment and retention rate of 38% and 84% were observed. Both strata maintained total skeletal muscle mass. Small reductions in body mass index, hip circumference, and percentage body fat, and small increases in hand grip strength and exercise capacity among subjects in both strata were observed. No significant differences were observed between strata; however, significant increases in exercise capacity and global health status for S2 were observed from baseline to 12 wk. FLW Program is a feasible mode of delivering nutrition and exercise intervention to cancer survivors and it appears that there are no barriers to implementing this program early during chemotherapy. Hence, the additive effect of gains achieved over a longer duration is promising and this should be explored in randomized controlled trials adequately powered to observe clinically and statistically significant improvements in relevant outcomes.

Late effects of oxaliplatin-induced peripheral neuropathy (LEON)--cross-sectional cohort study of patients with colorectal cancer surviving at least 2 years.

OBJECTIVES: Oxaliplatin accumulates in dorsal root ganglia, causing an axonal neuronopathy. Symptoms include numbness, pain and gait disturbance which may persist and impact on quality of life (QOL). Despite widespread use of this drug, its late effects and patient satisfaction outcomes have not been widely reported. Furthermore, there has been limited qualitative research published in this area. The objectives of this study were to establish the incidence and clinical impact of chronic peripheral neuropathy. METHODS: We conducted a cross-sectional observational study of patients who started oxaliplatin treatment at least 2 years prior to study commencement. Patients were assessed in three ways: clinical assessment encompassing neurological examination and nerve conduction studies to calculate a total neuropathy score (TNS); self-reported assessment via validated questionnaires; and assessment by recorded interview. The clinical and questionnaire-based assessments were analysed quantitatively and the interview data used for qualitative assessment. RESULTS: Twenty-five patients consented to participate. The mean starting dose of oxaliplatin given was 92 mg/m(2). The cumulative dose received ranged from 375 to 2,400 mg, with a mean cumulative dose of 1,515 mg. Oxaliplatin was ceased due to neuropathy in six patients (24 %), after a mean of 9 cycles of treatment. Modified TNS ranged from 1 to 15 with a mean of 9.5. There was a statistically significant correlation between cumulative oxaliplatin dose and TNS. Quality of life and functional impact questionnaires showed mildly lower physical quality of life, higher pain scores and functional impairment secondary to sensory deficit. Qualitative analysis demonstrated variable bio-psycho-social effects of chronic neuropathy but, importantly, highlighted that many patients felt they had been insufficiently warned of the risk of neuropathy. Despite this, the majority was satisfied with their decision to receive the drug. CONCLUSION: Many patients objectively demonstrated mild to moderate oxaliplatin neuropathy >2 years post-treatment. The majority of patients did not recall being warned of the risks of chronic peripheral neuropathy. Many of those who recall being warned did not feel sufficient emphasis was placed on the issue. Despite a varying burden of neuropathic symptoms, the majority of patients were highly satisfied with their decision to receive oxaliplatin.

Is self-management feasible and acceptable for addressing nutrition and physical activity needs of cancer survivors?

BACKGROUND: Self-management is recommended for patients with chronic conditions, but its use with cancer survivors is underexplored. Optimal strategies for achieving lifestyle changes in cancer survivors are not known. OBJECTIVE: We aimed to determine feasibility, acceptability and preliminary efficacy of self-management-based nutrition and physical activity interventions for cancer survivors. DESIGN, SETTING AND PARTICIPANTS: Adult survivors (n = 25) during (Group 1 , n = 11) or post (Group 2, n = 14)-curative chemotherapy for solid tumours, most (n = 20, 80%) with breast cancer, were recruited prospectively from a single clinical centre. INTERVENTION: The Flinders Living Well Self-Management Program, a generic self-management care planning programme, was utilized to establish patient-led nutrition and exercise goals within a tailored 12-week intervention. Fortnightly progress reviews occurred with assessments at baseline, 6 and 12 weeks. RESULTS: Most participants (84%) found the intervention acceptable/very acceptable. Both groups showed a trend towards significant improvement in the self-management capability 'knowledge about changing risk factors' (P = 0.047); Group 2 showed a trend towards significantly improved 'psychological impacts' (P = 0.007). Goal ratings improved for both groups (P = 0.001). Quality of life improved for both groups for emotional functioning (P = 0.03). Physical functioning improved for Group 2 (P = 0.05); however, most symptom domains worsened for Group 1, as expected given their treatment stage. DISCUSSION AND CONCLUSIONS: Self-management interventions are feasible for this population. In particular, building self-management capacity during the active phase of patients' cancer treatment provides health and psychosocial benefits. Larger randomized controlled trials are required to further determine efficacy. Further translational research is also needed to determine acceptability,feasibility, enablers and barriers for clinicians embedding this approach into routine cancer survivorship care.

Returning to work following curative chemotherapy: a qualitative study of return to work barriers and preferences for intervention.

PURPOSE: This study aimed to explore barriers to return to work (RTW) and preferences for intervention and support for cancer patients treated with curative intent from the perspectives of cancer survivors and oncology health professionals. METHODS: Participants attended a focus group (N = 24) or an individual interview (N = 14). A topic guide and a semi-structured recorded interview format were used to gather data, which were later transcribed and analysed for global themes and subthemes. RESULTS: With regard to barriers, the global theme 'work capacity' captured an array of barriers encompassing financial pressure, preparedness for work, lack of confidence as well as other key physical, practical and psychosocial barriers. Participants expressed a preference for RTW models that focus on objective and structured assessment whilst allowing for flexibility to address individual needs. CONCLUSIONS: Cancer survivors perceive multiple barriers when attempting to RTW. These barriers were perceived to impact upon work capacity, where 'capacity' was defined broadly to include practical, physical and psychosocial concerns. RTW is an important concern for cancer survivors and structured RTW interventions should be incorporated into the care of cancer survivors.

Pemetrexed-Induced Interstitial Pneumonitis: A Case Study and Literature Review.

Pemetrexed is a new-generation antifolate drug, now widely used in patients with non-small cell lung cancer (NSCLC). We report a case of pemetrexed-induced interstitial pneumonitis, and review the literature of eight previously reported cases. As pemetrexed is now a widely used chemotherapeutic agent, it is important to be aware of rare adverse events related to its administration.

Phase 1 clinical trial of the novel proteasome inhibitor marizomib with the histone deacetylase inhibitor vorinostat in patients with melanoma, pancreatic and lung cancer based on in vitro assessments of the combination.

PURPOSE: Combining proteasome and histone deacetylase (HDAC) inhibition has been seen to provide synergistic anti-tumor activity, with complementary effects on a number of signaling pathways. The novel bi-cyclic structure of marizomib with its unique proteasome inhibition, toxicology and efficacy profiles, suggested utility in combining it with an HDAC inhibitor such as vorinostat. Thus, in this study in vitro studies assessed the potential utility of combining marizomib and vorinostat, followed by a clinical trial with the objectives of assessing the recommended phase 2 dose (RP2D), pharmacokinetics (PK), pharmacodynamics (PD), safety and preliminary anti-tumor activity of the combination in patients. EXPERIMENTAL DESIGN: Combinations of marizomib and vorinostat were assessed in vitro. Subsequently, in a Phase 1 clinical trial patients with melanoma, pancreatic carcinoma or Non-small Cell Lung Cancer (NSCLC) were given escalating doses of weekly marizomib in combination with vorinostat 300 mg daily for 16 days in 28 day cycles. In addition to standard safety studies, proteasome inhibition and pharmacokinetics were assayed. RESULTS: Marked synergy of marizomib and vorinostat was seen in tumor cell lines derived from patients with NSCLC, melanoma and pancreatic carcinoma. In the clinical trial, 22 patients were enrolled. Increased toxicity was not seen with the combination. Co-administration did not appear to affect the PK or PD of either drug in comparison to historical data. Although no responses were demonstrated using RECIST criteria, 61% of evaluable patients demonstrated stable disease with 39% having decreases in tumor measurements. CONCLUSIONS: Treatment of multiple tumor cell lines with marizomib and vorinostat resulted in a highly synergistic antitumor activity. The combination of full dose marizomib with vorinostat is tolerable in patients with safety findings consistent with either drug alone.

Small cell lung cancer: patterns of care and their influence on survival - 25 years experience of a single Australian oncology unit.

AIM: Evidence supporting improved outcomes for small cell lung cancer (SCLC) in recent decades is limited. This study aimed to identify patterns of care and survival over two time periods; 1 January 1987 to 31 December 1996 (cohort A) and 1 January 1997 to 31 December 2006 9 (cohort B). METHODS: Patients' characteristics, management and outcome data were extracted from the Hospital Cancer Registry and clinical records. Survival analysis was determined using the Kaplan-Meier method and the log-rank test. Factors influencing survival outcome were assessed using Cox proportional hazards regression. RESULTS: The total number of patients was 392 (224 in cohort A, 168 in cohort B). Overall 38% patients in cohort A and 24% in cohort B had limited stage (LS) disease at diagnosis. Combined chemoradiotherapy for LS increased from 5% in cohort A to 65% in cohort B. Overall 19% of patients in cohort A and 24% in cohort B received symptomatic treatment alone (STA). Median survival for LS in cohort B was significantly higher (19.5 months), than in cohort A (11.8 months) (P = 0.03). In extensive stage (ES) disease, median survival was 6.2 months in cohort A and 4.3 months in cohort B (P = 0.7). Variables for poorer outcome were STA, male gender, poor performance status, ES and whether the diagnosis was made in the earlier time period in cohort A. CONCLUSION: Outcomes for LS SCLC have improved with combined chemoradiotherapy, in keeping with worldwide data. The trends may also reflect recent improvements in staging and standardization of treatment. The outcome for ES-SCLC remains poor.