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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.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.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).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.

ContextChronic inflammation, characterized by prolonged elevated inflammation markers, is linked to several chronic conditions. Diet can influence the levels of inflammation markers in the body.ObjectiveThe aim of this systematic review was to assess the effects of anti-inflammatory diets on 14 different inflammation markers in adults.Data SourcesThis systematic review conducted searches using Medline, PubMed, EMCare, Cochrane, and CINAHL, to locate randomized controlled trials (RCTs).Data ExtractionTwo researchers independently screened 1537 RCTs that measured changes in inflammation markers after prescription of an intervention diet.Data AnalysisIn 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, -1β, -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.ConclusionsThere 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.

Influenza virus infection has significant morbidity and mortality in patients with medical co-morbidities who are also immunosuppressed. The efficacy of the seasonal influenza vaccine has not been well studied in patients receiving chemotherapy. We assessed the efficacy of seasonal influenza vaccine in patients with non-haematological malignancy on active treatment (chemotherapy and targeted therapy). A prospective single arm, open label study with 53 patients with non-haematological cancers recruited during the 2011 and 2012 influenza seasons. Participants had one dose of 2011/2012 trivalent vaccine containing strains A/California/7/2009(H1N1), A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008 (Fluvax) prior to or in-between treatment cycles. Haemagglutination inhibition antibody (HIA) titres in serum were measured at baseline 3, 6 and 24 weeks. Primary endpoint: seroconversion rate (SCR) at 3 weeks. Secondary endpoints: Seroconversion was defined as postvaccination ≥ 4-fold increase in HIA titre and sero-protection defined as a HIA ≥ 1:40. The SCR at 3 weeks were 35%, 30% and 22.5% to the H1N1, H3N2 and B/Bris strains, respectively. There were no new cases of late SC at 6 weeks or 24 weeks. The SPR at 3 weeks were 72.5%, 65% and 40%, respectively, to H1N1, H3N2 and B/Bris. The SPR at 24 weeks to H1N1, H3N2 and B/Bris were 40%, 52.5% and 17.5%, respectively. Patients on various solid tumour treatments achieve sero-protection rate congruent with the general population. The sero-protection HIA titres were not sustained at 24 weeks postvaccination.

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.

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.

Purpose/objective(s) Oral Mucositis (OM) is a common, painful, and costly toxicity associated with cytotoxic chemoradiation regimens used to treat HN scores were centrally assigned. The primary efficacy endpoints included the incidence and duration of SOM (WHO grades 3 or 4) vs historical controls. PD tracking measured total ROS/RNS, GSH/GSSG, regulation in plasma and buccal epithelial cells. Results 17 pts completed the 50, 100 and 150mg/day with no safety issues. No early dose limiting toxicity (DLT) or serious Adverse Event linked to ST-617 were observed. AEs observed were mainly nausea which is usually associated with CRT as expected. As overall SOM incidence (baseline to the last day of radiation) of 50% was less than expected and was related to ST-617 dose: 50 mg/day 83% (n = 6); 100 mg/day 33% (n = 9); 200 mg/day 33% (n = 3). The 100 mg/day dose was well tolerated with no grade 4 OM. No CRT dose interruptions or delays due to OM were noted Total ROS/RNS levels in plasma and buccal samples show significant decrease with increased ST-617 dosing from 50 to 100 mg/day. ST-617 did not alter tumor response at 1 year post-CRT (n = 17). Conclusion ST-617 administration was safe at all doses tested. The course and severity of patients treated with ST-617 compared favorably with historical controls. A dose-response effect on SOM incidence was noted. Mechanistic correlation between ROS/RNS levels was seen. A randomized, controlled, double blind trial is planned with the recommended dose of 100mg/day.

TPS8600 Background: Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor characterized by early metastasis and a high recurrence rate with currently available treatment options. Although SCLC is generally sensitive to initial chemotherapy, responses are not durable and most patients eventually relapse. Prognosis is poorer in the relapsed/refractory (R/R) setting and currently available treatment options, including checkpoint inhibitors, are associated with a median overall survival of 2-9 months (Chauhan 2020; Trigo 2020; Chung 2020). Approximately 15% of patients have a TP53 wild-type ( TP53WT) gene. In patients with extensive-stage SCLC, TP53WT is paradoxically associated with an inferior response to chemotherapy (Dowlati 2016). Thus, the presence of TP53WT may help identify a small subset of patients with an even greater unmet need. Murine double minute 2 (MDM2) is the key negative regulator of the tumor suppressor protein, p53, which can induce apoptosis of malignant cells by shifting the balance between prosurvival and proapoptotic BCL-2 family members. In SCLC cell lines, MDM2 inhibition restored p53 function leading to downregulation of prosurvival Bcl-2 and Mcl-1 proteins, and upregulation of the proapoptotic Bim protein, thereby inducing cancer cell death (Yu 2019). Navtemadlin (KRT-232) is a potent, selective, orally available MDM2 inhibitor that restores p53 function to drive apoptosis of TP53WT malignancies. Treatment with navtemadlin may be an effective strategy for patients with TP53WT SCLC. Methods: The open-label, multicenter Phase 2 KRT-232-112 study (NCT05027867) is evaluating navtemadlin in TP53WT patients with R/R SCLC. Eligibility criteria include age ≥18 years, ECOG performance status ≤2, presence of measurable disease and demonstrated radiographic progression after ≥1 prior platinum-containing therapy with no curative therapy available. Patients must have received a checkpoint inhibitor if available and not contraindicated. Patients with symptomatic or uncontrolled central nervous system metastases or those with prior MDM2 inhibitor treatment will be excluded. In part 1 of the study, approximately 20 patients will be randomly assigned to receive oral navtemadlin once daily in 21-day cycles at 240 mg 7 days (D) on/14D off (Arm A) or 180 mg 7D on/14D off (Arm B) until disease progression or unacceptable toxicity. In part 2, an additional 18 patients will be enrolled in each arm selected for expansion. The primary endpoint is objective response rate per RECIST v1.1. Secondary endpoints include duration of response, progression-free survival, overall survival, disease control rate, and safety. This trial is ongoing and will enroll patients at approximately 40 global sites. Clinical trial information: NCT05027867.

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.

BackgroundImmune 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 presentationWe 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.ConclusionsA 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.

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.

6075 Background: OM is a common, painful, and costly toxicity associated with cytotoxic regimens used to treat H&N cancers, which may result in radiotherapy treatment interruptions to negatively impact tumor control. There are currently no approved interventions to successfully prevent or delay OM onset among patients being treated with radiation therapy, with or without concomitant chemotherapy (CRT). Oxidative stress is a critical event in OM’s pathogenesis. Through its effect on Nrf2, ST-617 has marked anti-oxidative activity/properties. Supportive Therapeutics is developing ST-617, a dithioethione, for the attenuation of OM onset, duration and severity. The objective of this trial was to assess the safety, tolerability, PK, PD and efficacy of ST-617 in patients at high risk of severe OM (SOM). Methods: A dose escalation trial in which ST-617 administered as an oral suspension, 1-2 hours before the administration of daily RT fractions was performed at 9 study sites in South Africa and Australia. Eighteen patients with diagnoses of oral or oropharyngeal CA were enrolled (up to 6 pts/dose). Patients received concomitant cisplatin either weekly or tri-weekly. ST-617 was administered 3 days prior to CRT, and then continuing daily until the end of treatment. Safety outcomes, using CTCAE criteria (v 4.03) were used. Dose escalation occurred in the absence of toxicity. OM occurrence and severity were assessed by trained and validated evaluators using WHO, NCI-CTC and RTOG criteria; scores were centrally assigned. The primary efficacy endpoints included the incidence and duration of SOM (WHO grades 3 or 4) vs historical controls. PD tracking measured total ROS/RNS, GSH/GSSG, regulation in plasma and buccal epithelial cells. Results: 17 pts completed the 50, 100 and 150mg/day with no safety issues. No early dose limiting toxicity (DLT) or serious Adverse Event linked to ST-617 were observed. AEs observed were mainly nausea which is usually associated with CRT as expected. The 100 mg/day dose has been well tolerated with no grade 4 OM. No CRT dose interruptions or delays due to OM has been observed. Total ROS/RNS levels in plasma and buccal samples show significant decrease with increased ST-617 dosing from 50 to 100 mg/day. Conclusions: ST-617 administration was safe at all doses tested. The course and severity of patients treated with ST-617 compared favorably with historical controls. Mechanistic correlation between ROS/RNS levels was seen. A randomized, controlled, double blind trial is planned with the recommended dose of 100mg/day. Clinical trial information: 20180138.

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. Refereed/Peer-reviewed

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.

e16796 Background: Locally advanced pancreatic adenocarcinoma (LAPC) carries a poor prognosis with median overall survival of 12-18m. The optimal treatment is controversial. Nab-paclitaxel is active in advanced pancreatic cancer and has exhibited radio-sensitising anti-tumour efficacy. Methods: We conducted an investigator-initiated open-label, phase-I dose escalation trial of nab-paclitaxel with standard external beam radiotherapy (EBRT). All patients had biopsy-proven, untreated, localised, inoperable pancreatic adenocarcinoma; Patients received nab-paclitaxel on a weekly schedule for 6 weeks, concurrently with EBRT. A 3+3 cohort design was employed, with doses of nab-paclitaxel increasing from 25 mg/m2 (cohort 1), to 50 mg/m2 (cohort 2), 75 mg/m2 (cohort 3) and 100 mg/m2 (cohort 4). This principal objective of the trial was to establish the maximum tolerated dose (MTD) of nab-paclitaxel given concurrently with radiotherapy. Secondary objectives included safety and efficacy evaluation, including response rate, median PFS, median and 1- year OS. Results: Fourteen patients were recruited to the study, with a median age of 69 (range 40-86). 69% had a head or neck of pancreas tumour. Majority of patients had grade 1 or 2 toxicities with nausea (92%), fatigue (69%), diarrhoea (54%) and vomiting (54%) being the most common. Three patients were recruited in each of the first three cohorts, without any dose limiting toxicities (DLT). In cohort 4, DLT of febrile neutropenia and enterocolitis was observed in patient 1. The cohort was expanded with a subsequent DLT of febrile neutropenia and enterocolitis observed in patient 5. Both DLT events lead to death (grade 5). The MTD and recommended phase II study dose has been established as 75mg/ m2. The disease control (PR and SD) rate was 67%, median PFS 4.7 months (95% CI 2.5-27.5), 1 year OS 43% and median OS 11.4 months (95%CI 6.37-25.2). Conclusions: The combination of weekly nab-paclitaxel and fractionated radiation was generally well-tolerated at doses of nab-paclitaxel below 100 mg/m2. There were two treatment related DLTs leading to death in the nab-paclitaxel 100 mg/m2 cohort. The MTD and recommended phase II study dose for nab-paclitaxel combined with radiation therapy in the treatment of LAPC is 75mg/m2. Clinical trial information: ACTRN12613001013752 .

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.

Chronic benign pleural effusion (BPE) is a rare complication of concurrent chemoradiotherapy (CRT) for inoperable stage IIIA non-small-cell lung cancer (NSCLC). This report presents three cases of BPE, the workup to differentiate this benign condition from recurrence of cancer and recommends a pleural biopsy as part of the diagnostic process. These inflammatory exudates often remain indolent, and may not require drainage or surgical intervention. In the absence of clinical, radiological and pathological evidence of recurrent disease, we recommend clinicians manage these patients expectantly, using regular clinical assessment and imaging.

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.We aimed to determine feasibility, acceptability and preliminary efficacy of self-management-based nutrition and physical activity interventions for cancer survivors.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.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.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.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.

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.

e23076 Background: Chemotherapy-induced premature menopause is a distressing side effect of cancer treatment. Currently there are no validated tools to predict the loss of ovarian function. Anti-Mullerian hormone (AMH) in healthy women correlates with ovarian reserve and predicts menopause but its utility in chemotherapy-treated patients is underexplored. We examined the utility of AMH levels as a predictor of chemotherapy-induced amenorrhea at 1-year post chemotherapy - a reliable surrogate for chemotherapy-induced menopause. Methods: Premenopausal women, 45 years or younger, about to receive curative chemotherapy for breast cancer or lymphoma, without ovarian suppression, were assessed for menopausal symptoms using Menopausal Symptom Score (MSS), quality of life (QOL) using EORTC – QLQ-C30 questionnaire, and had serum AMH, oestradiol, FSH, LH collected prior to first chemo, and at 3 and 6 weeks, at completion and 12 months after chemotherapy. Results: Twenty-two premenopausal women, median age 40.5 (37-43) were enrolled. Twenty became amenorrhoeic during chemotherapy and four had return of menses at 1 year after treatment completion. Median AMH level at baseline was 12.9 pmol/L (IQR 5.2 – 26.5), fell sharply following first chemotherapy and remained low at < 3pmol/L (IQR < .3 ) at 1 year with only 2 subjects with AMH levels above 3 pmol/L. Women who regained menses at 12 months had higher baseline AMH than those who remained amenorrheic (p < 0.001). Older age was associated with lower AMH at baseline and at 1 year. Median MSSs increased significantly at 1 year: 0.8 (IQR 0.5-1.8) versus 0.3 (IQR 0-0.4) (p = 0.5). While there was no significant change in QOL scores between baseline and 1 year, there was a significant negative correlation between menopausal symptom score and QOL at 1 year (p = 0.03). Conclusions: In this small study, pre-treatment AMH correlated with amenorrhea at 1-year post chemotherapy suggesting potential role of AMH levels in counselling women regarding their reproductive potential post chemotherapy. Further research in a larger sample of women is needed.

A retrospective case notes review was performed to determine compliance with screening for undetected pregnancy prior to commencement of chemotherapy at Flinders Medical Centre. All female patients aged 18-55 who commenced chemotherapy between January and December 2014 were included. During the first 12 months, for women identified as having childbearing potential, pre-chemotherapy pregnancy screening was performed only in 40% of patients under 40 years and in 20.5% of the entire age range.

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.

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.

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.

e18554Background: The management of Jehovah’s Witnesses (JW) who have oncological problems presents many different challenges both at the therapeutic and ethical level due to refusal of blood and b...

e18176 Background: Jehovah's Witness (JW) patients with cancer present unique challenges due to their refusal of blood and blood products which limits supportive care options in the setting of cancer treatment. This study was aimed at determining their cancer specific outcomes. Methods: A retrospective analysis of case records of JW with solid tumors presented between 2005 and 2015 was conducted. Patient demographic data, diagnosis, treatment details and survival outcomes were collected and analysed. Results: A total of 63 JW were identified (39 females; 24 males); median age was 70 years (25-90). The most common cancer was breast (n=16) followed by colorectal (n=10). 27 JW had advanced disease (TNM stage 4), 48 patients had ECOG 0-1 and 22 JW had anaemia (Hb

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. 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. Twenty-five patients consented to participate. The mean starting dose of oxaliplatin given was 92 mg/m2. 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. 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.

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. 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. 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. 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.

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).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.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.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.

This was a phase I trial to determine the maximum tolerated dose (MTD) of a marine lipid extract from the New Zealand green-lipped mussel (Perna canaliculus), as an inhibitor of 5- and 12-lipo-oxygenase enzymes, in patients with advanced breast and prostate cancers.This was an open-labelled, phase I, dose-escalation study. Proprietary form of green-lipped mussel lipid extract (GLMLE), 260-mg capsule, was administered on a twice-daily schedule, orally. Patients remained on study until disease progression or unacceptable toxicity.From December 1999 to May 2003, 17 patients were enrolled. Fifteen of them were male with advanced prostate cancer and two were female with advanced breast cancer. The median age of the patients was 74 years (range 56-85 years). Sixteen patients were assessable for adverse events and dose-limiting toxicity (DLT). Reason for withdrawal from the study included progressive disease (n = 12), death (n = 1) and DLT (n = 3). Two patients had evidence of grade 4 hepatic dysfunction. The MTD was not reached. There were no objective tumour responses noted.GLMLE appears to be a well-tolerated compound in this setting. There appears to be no objective benefit. However, grade 3/4 hepatic toxicity noted in two patients is of concern and should be considered while evaluating patients taking GLMLE or while designing studies with this agent.

6541 Background: Research involving archival tumor tissue has become increasingly important in molecular oncology and has led to improved therapeutics. There are important ethical considerations for such research. We examined the attitudes of patients with cancer toward research that used their tumor tissue. Methods: From January to April 2012, consecutive patients with cancer attending the outpatient clinic of the Flinders Cancer Centre were asked to complete a 27-item investigator-developed questionnaire. The questionnaire included 4 sections: 1) demographics, 2) understanding of cancer research, 3) donation of tumor tissue and 4) ethical issues. Results: 118 patients completed the questionnaire, 53% male and mean age 61. 95% stated that they believed that research involving tumor tissue was beneficial to the public and to cancer patients in the future. 72% responded such research could have a direct benefit for them. 94% would allow their tissue to be used for future research. 86% stated that nothing would prevent them from allowing tissue research. Only14% believed that they needed to be informed about the research. Only 5% were of the opinion that the tissue still belonged to them after it had been removed from their body. 72% were not concerned where their tissue was sent for research, whilst 19% preferred that the research be conducted in Australia. When asked about the use of tissue for research after death, 10% stated that their prior approval was required, less than 1% wanted their family members to approve the research whilst 80% felt that ethics committee approval without individual consent was acceptable. Less than 1% stated that the tissue should be destroyed after death. 69% expressed a preference for the research findings to be available to everyone without commercialisation. Conclusions: The majority of patients permit the use of their tumor tissue for research with ethical approval but without the expectation of individual consent. After death, most patients did not want to have their tissue discarded and were accepting of research without the need for prior consent or family approval. We need to understand the preferences of the majority of patients in determining optimal policy for correlative tumor tissue research.

e19550 Background: Low serum vitamin D in cancer patients has been associated with inferior cancer outcomes and bone loss. The impact of chemotherapy on vitamin D levels is not known. We examined serum vitamin D levels during chemotherapy to identify magnitude and predictors of change. Methods: A prospective study of chemotherapy naïve patients commencing chemotherapy in two different sun exposure areas. Vitamin D (25(OH)D) deficiency was defined as ≤25 nmol/L and insufficiency 26-50 nmol/L. Demographic data, nutrition, sun exposure, season and biochemical parameters were collected at baseline 6 weeks (6W) and 12 weeks (12W) since commencement of treatment. The effects were assessed using a multivariate multilevel linear regression model that also included age, gender and BMI. Results: 82 Caucasian and 3 indigenous patients were enrolled. Median age was 57 (21-85) years. Forty-nine (58%) were female; 54 (65%) were treated with curative intent. Tumours included 29 (34%) breast,12 (14%) colorectal, 9 (11%) lymphomas, 7 (8%) leukemias, 7 (8%) lung, 5 (6%) ovarian, 3 (4%) testis, 3 (4%) unknown primary and 10 (11%) others. Median weight was 75 kg (50-151) and median BMI was 26.9 kg/m2 (17.7- 44.5). Seventy-six (89%) and 55 (65%) patients were receiving chemotherapy treatment at 6W and 12W respectively. Mean (±SD) serum 25(OH)D at baseline was 49.2±22.3 nmol/L. Ten (12%) patients were vitamin D deficient at baseline and a further 33 (41%) had insufficient levels. Mean serum 25(OH)D status was higher in higher sun exposure locations (61.9±22.1 nmol/L vs 42.2±19.2 nmol/L, p

e15592 Background: Early stage endometrial cancers have a good prognosis. However, these are a heterogeneous group of patients with varying recurrence risk (RR). Methods: Retrospective analysis of patients, diagnosed and treated, with endometrial cancer at Flinders Medical Centre, South Australia, from 1 January 2000 until 31 December 2009. Demographic, clinical and pathologic factors were analyzed to determine association with RR. Results: A total of 152 women with a median age of 65 years were analysed. Surgery was the primary intervention in 146 patietns (96%). Optimal debulking status was achieved in 113 patients (74.3%). Endometriod adenocarcinoma was the most common histological subtype (67%). Other subtypes included adenocarcinoma (18.4%), papillary serous carcinoma (3.9%), carcinosarcoma (1.9%), mixed (4.6%) and other (3.9%). Fifty-eight patients had grade 1 tumour, 55 grade II and 36 grade III. Out of 103 patients who had their lymphovascular space invasion (LVSI) status assessed, 21 (20.4%) were...

Background: The bi-cyclic structure of NPI-0052 differentiates it from other proteasome inhibitors which are structurally polypeptide based, leading to its differential properties of rapid, broad and prolonged inhibition of all 3 proteolytic sites, and unique proteasome inhibition, toxicology and efficacy profiles. Preclinical studies indicated an increased therapeutic ratio with activity in hematologic and solid tumor malignancies leading to the initiation of Phase 1 clinical trials. These biologic differences also led to the question of whether twice weekly administration schedule, as is typical for other proteasome inhibitors, or more convenient once weekly schedule would be preferable. Materials and Methods: Patients with solid tumor, lymphoma, leukemia or myeloma diagnoses failing after standard therapies were given NPI-0052 intravenously on a weekly or twice weekly arm in the dose escalation portion of this study. Subsequently 10 patient Recommended Phase 2 dose Cohorts of patients with lymphomas, CLL and myeloma are enrolled. Proteasome inhibition and pharmacokinetics are also assayed in whole blood, and/or peripheral blood mononuclear cells (PBMC) on Day 1 and multiple subsequent time points. Results: 44 patients have been enrolled into this study. Notable adverse events have been fatigue, parosmia/dysgeusia, transient peri-infusion site pain, lymphopenia, headaches, dizziness / unsteady gait, closed-eye visuals, cognitive changes. Peripheral neuropathy, neutropenia and thrombocytopenia do not appear to be induced. Pharmacokinetic data indicate a short T1/2 and large Vss. Proteasome inhibition assays demonstrated inhibition of chymotrypsin-like activity of up to 88% Day 1 and 100% Day 15. Inhibition accumulates initially in whole blood presumably secondary to the inability of RBC to synthesize new proteasomes, whereas inhibition recovers over several days in PBMC further leading the question as to an optimal dosing regimen. Stable disease, regression or response, have been reported in mantle cell lymphoma, myeloma, Hodgkin's lymphoma, cutaneous marginal zone lymphoma, follicular lymphoma, sarcoma, prostate carcinoma and melanoma. Conclusions: NPI-0052 produces expected or greater levels of proteasome inhibition in patient blood samples, with a toxicity profile that is dissimilar to what is reported with other proteasome inhibitors. The profile of the proteasome inhibition, toxicity and efficacy profiles that have been revealed during this clinical trial and correlative studies reveals further basis and hypothesis as to what an optimal dosing regimen might be, which is being assessed in this study. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C33.

Abstract 2693 Poster Board II-669 Background: NPI-0052 is a proteasome inhibitor with a novel bicyclic structure (other proteasome inhibitors in clinical use are peptide based). Preclinical studies indicate rapid, broad and prolonged inhibition of all 3 catalytic sites of the proteasome, and subsequently unique proteasome inhibition, signal transduction, toxicology and efficacy profiles. Taken together these suggest the potential for improvements in therapeutic ratio and activity in hematologic and solid tumor malignancies. Materials and Methods: Patients with solid tumor, lymphoma, leukemia or myeloma diagnoses without standard treatment options have been treated with IV NPI-0052 on one of two arms (weekly or twice weekly) in this 3+3 design dose escalation study. This is followed by 10 patient Recommended Phase 2 dose Cohorts of patients with lymphomas, CLL and myeloma respectively. Proteasome inhibition (pharmacodynamics) and pharmacokinetics are also assayed in whole blood, and proteasome inhibition in peripheral blood mononuclear cells (PBMC). Results: 44 patients have been treated with NPI-0052 at doses ranging from 0.075 mg/m2 to 0.9 mg/m2. Common adverse events include fatigue, parosmia/dysgeusia, transient peri-infusion site pain, lymphopenia, headaches, dizziness / unsteady gait, closed-eye visuals, cognitive changes. Incidence and grade of these events correlate with dose, being quite tolerable at the MTD of 0.7 mg/m2 on the weekly dosing arm. An MTD has not yet been determined for the twice weekly dosing arm. Pharmacokinetic data has demonstrated a rapid elimination half-life ( Conclusions: NPI-0052 produces dose-dependent pharmacologic effects through the predicted efficacious range, while producing a toxicity profile that is dissimilar to what is reported with other proteasome inhibitors (notably deficient in peripheral neuropathy, neutropenia and thrombocytopenia) in spite of producing equal or greater proteasome inhibition. These data indicate a broad range of potential uses, and led to additional studies in hematologic malignancies and solid tumors alone and in combination. Disclosures: Longenecker: Nereus Pharmaceuticals: Employment. Palladino:Nereus Pharmaceuticals: Employment, Equity Ownership. Lloyd:Nereus Pharmaceuticals: Employment, Equity Ownership. Neuteboom:Nereus Pharmaceuticals: Employment, Equity Ownership. Spear:Nereus Pharmaceuticals: Employment, Equity Ownership.

e15100 Background: Irinotecan and 5-Fluorouracil based combination is an effective regimen for mCRC. Capecitabine, an oral fluoropyrimidine, is a convenient alternative to intravenous 5- Fluorouracil. This study aims to systematically review all published and unpublished controlled phase II and III trials of XELIRI combination, used in first line treatment of mCRC, reported from 2000–2008, to describe its efficacy and safety. Methods: A literature search of MEDLINE, EMBASE, CINAHL and proceedings from ASCO, ESMO and WGIC was conducted. The primary end point was response rate (RR), secondary endpoints include: time to progression (TTP), overall survival (OS) and toxicity. Results: Thirty non-randomised phase II trials (n = 1380) along with 6 randomised phase II and 3 phase III trials, were included (pooled n = 1478). The daily dose of capecitabine ranged from 1,800 mg/m2 to 2,500 mg/m2 for 7 to 14 days per cycle and the dose of irinotecan varied from 180mg/m2 to 350 mg/m2, over a 3 week period per cycle. Amongst the non-randomised studies, the median patient age was 61 years (53–72).The median RR was 46.75% (25–78%). The median reported TTP was 7.9 months (mo) (5- 9.9 mo) and the median OS was 15.6 months (7–24.8 mo). Grade 3–4 toxicity incidence was: diarrhoea (21.5%), neutropenia (12%), vomiting (12.5%), fatigue (6%) and Hand-foot syndrome (6%). The pooled incidence of febrile neutropenia was 2.5%. Amongst the randomised trials, the comparator regimens were XELOX or FOLFIRI. Median age was 65 years (61–74). RR for XELIRI was 39% (34–56%) compared to 47% (27–61.8%) for the non XELIRI comparator arms. Median reported TTP was 8.2 mo (5.7–12.5 mo) for the XELIRI arms and 9.2 mo for the comparator arms. Conclusions: XELIRI is an effective and feasible regime in the first line management of mCRC. However the optimal role of this combination remains to be established. No significant financial relationships to disclose.

e20577 Background: Elderly patients are underrepresented in clinical trials, yet account for significant group with small cell lung cancer (SCLC). We examined if the age of the patients, 70yrs, impacted outcome. Methods: SCLC pts were identified by searching the hospital cancer registry from 1999 to 2009. Pt characteristics, management and outcomes were collated by reviewing clinical records. Survival analysis was performed. Results: From 168 SCLC pts, 49 (27 males, 22 females) had limited stage (LS) and 113 (71 males, 42 females) extensive stage (ES) SCLC. LS cohort, 27 pts were 70yrs. The overall group survival was not statistically different, with median overall survival of 12.4 months for 70yrs (p=0.064). However, 44 pts who had active treatment, including chemoradiotherapy, chemotherapy alone, radiotherapy alone, there was statistically improved survival between 70yrs of 12.8 months vs 8.2 months (p=0.05). There was no significant difference in proportion of pts who received active treatment between the two groups (96.2% vs 95.4% p =0.882). The number of pts completing treatment was not statistically different between the two age groups (70.8% vs 54.5% p = 0.53) In the ES cohort, 45 pts were 70yrs. The overall group survival was significantly worse in the >70yrs with MOS 3.8 months for >70yrs and MOS 6.9 for 70yrs 5.9 months (p= 0.088). Significantly less pts >70yrs vs 70yrs, patients >70yrs had reduced survival, this may be related to patient factors or tumour biology. In ES SCLC, comparing patients70yrs, patients >70yrs had worse survival overall, less likely to receive active treatment and less likely to complete treatment, again this may reflect a difference in patient factors or tumour biology.