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Survival with advanced pancreatic cancer is less than 12 months. Pancreatic exocrine insufficiency may contribute to pancreatic cancer-related cachexia, via nutrient malabsorption. We aimed to determine the feasibility of prescribing pancreatic extract (Creon®) for patients with advanced pancreatic cancer. Patients with advanced pancreatic cancer, without frank malabsorption, were randomised in this feasibility study to pancreatic extract 50,000 units with meals and 25,000 units with snacks, or placebo. Standardised dietary advice was given. Anti-cancer and supportive care treatments were permitted. Outcomes included weight, body mass index (BMI), quality of life (QLQC30, PAN26), survival and nutritional assessment (PG-SGA). Eighteen patients were randomised before study closure due to slow recruitment. Baseline characteristics were well matched. Weight loss prior to randomisation was numerically greater in the pancreatic extract group (mean 0.7 vs 2.2 kg). Weight loss was numerically greater in the placebo group, however not significantly. No differences in BMI or nutrition score were seen. Quality of life did not differ between study groups. Median overall survival was 17 (95% CI 8.1–48.7) weeks in the control group, and 67.6 (95% CI 14.1–98.4) weeks in the pancreatic extract group (p = 0.1063). Only 17% (18/106) of potentially eligible patients were recruited, related to patient/family reluctance, rapid clinical deterioration and patients already prescribed pancreatic extract. A moderate pill burden was noted. Despite intriguing survival results, this study was not sufficiently feasible to proceed to a fully powered comparative study. A multi-centre study would be required to exclude a significant difference in outcomes.

e14029 Background: A significant delay in oncology patient journey through emergency department (ED) due to various reasons such as multiple specialists involved, difficulty in accessing timely advice from extremely busy inpatient/outpatient oncology teams, etc. In order to streamline admissions and discharges for oncology patients, a new model of care was created with the introduction of oncology nurse practitioner (ONP) at Calvary Mater Newcastle ED. This model operated during business hours three days a week with an aim to improve continuity of care, to enhance patients’ experience and meet organisations key performance indicators (KPIs). Limited research into the impact of these services on patient care and patient experience, particularly from service users’ perspective. Methods: A retrospective audit (6 months) has been undertaken to determine the impact of this model of care on time to specialty transfer, number of admissions versus discharges and patients representations through ED when ONP was available versus standard care. Results: During the audit period, ONP reviewed 149 patients. Fifty-four (36%) patients were discharged and of those 6 (11%) returned (within 28 days) with same or related issues. There was an average reduction in time to disposition planning for ED oncology patients of approximately 83 (193 vs 110) minutes when ONP was present at ED (one month review). Using a raw bed day costing, this resulted in a significant financial saving. Further cost analysis of this model is underway. Conclusions: The introduction of ONP into an acute care hospital ED has proven to be effective in terms of continuity of patient care, financial savings and assisted ED in meeting KPIs. The perception within the senior emergency management team is that this new model of care has been an unqualified success. ONP has rapidly and effectively joined emergency team and has seamlessly adjusted practice to the new environment. ED remains highly supportive of this new model of care. This model of care is one that could be translated easily to other specialities. Further analysis will be presented at the time of ASCO meeting.

Modafinil has been reported to benefit a subgroup of patients suffering severe fatigue while undergoing chemotherapy. Docetaxel is associated with fatigue that may lead to premature therapy withdrawal. We investigated whether modafinil could reduce fatigue during docetaxel chemotherapy.This multicenter, randomized, double-blind, placebo-controlled study evaluated the efficacy of modafinil in patients with metastatic prostate or breast cancer undergoing docetaxel chemotherapy (every 21 days; minimum dose 50 mg/m(2)). At the start of their third or subsequent chemotherapy cycle, patients with significant docetaxel-associated fatigue were randomized to receive concurrent modafinil 200 mg/day or placebo for 15 days ("treatment periods" (TP)). Docetaxel was continued for up to four further cycles. Fatigue was evaluated with the fatigue component of the MD Anderson Symptom Inventory (MDASI). The primary endpoint was cumulative MDASI area under the curve (AUC) during the first 7 days of study medication during TP1 and TP2.Evaluable data were available from 83 patients (65 with prostate cancer). There was no statistically significant difference between the two treatment arms for the primary endpoint (MSADI AUC3-10 35.9 vs 39.6; 95 % confidence interval -8.9, 1.4; P=0.15). Overall toxicity was comparable between treatment groups; however, the incidence of grade ≤ 2 nausea and vomiting was higher in the modafinil arm (45.4 vs 25 %).Assessing and managing chemotherapy-related fatigue remains a major challenge. There was a lack of difference between the two arms in the planned primary endpoint. However, there was a modest but consistent trend towards improvement of docetaxel-related fatigue in those treated with modafinil. Based on the study findings, modafinil for the treatment of fatigue associated with docetaxel chemotherapy elicits modest improvements. Larger, longer term, randomized, controlled studies are required to clarify the exact role of modafinil in the treatment of docetaxel-related fatigue.

The purpose of the present paper was to evaluate treatment outcome after conservative breast surgery or mastectomy followed by simultaneous adjuvant radiotherapy and cyclophosphamide, methotrexate and fluorouracil (CMF) therapy. Two hundred and sixty eight (268) patients were treated at two Australian and two New Zealand centres between 1981 and July 1995. One hundred and sixty-nine patients underwent conservation surgery and 99 had mastectomies. Median follow-up was 53 months. Conventionally fractionated radiation was delivered simultaneously during the first two cycles of CMF, avoiding radiation on the Fridays that the intravenous components of CMF were delivered. In conservatively treated patients, 5-year actuarial rates of any recurrence, distant recurrence and overall survival were 34.5 +/- 5.2%, 25.4 +/- 4.5% and 75.5 +/- 4.8%, respectively. Crude incidence of local relapse at 4 years was 6.3% and at regional/distant sites was 26.3%. Highest grades of granulocyte toxicity (< 0.5 x 10(9)/L), moist desquamation, radiation pneumonitis and persistent breast oedema were recorded in 10.7, 8.5, 8.9 and 17.2%, respectively. In patients treated by mastectomy, 5-year actuarial rates of any recurrence, distant recurrence and overall survival were 59.7 +/- 7.3%, 56.7 +/- 7.4% and 50.1 +/- 7%. The crude incidence of local relapse at 4 years was 5.6% and at regional/distant sites it was 45.7%. The issue of appropriate timing of adjuvant therapies has become particularly important with the increasing acknowledgement of the value of anthracycline-based regimens. For women in lower risk categories (e.g. 1-3 nodes positive or node negative), CMF may offer a potentially better therapy, particularly where breast-conserving surgical techniques have been used. In such cases CMF allows the simultaneous delivery of radiotherapy with the result of optimum local control, without compromise or regional or systemic relapse rates. Further randomized trials that directly address the optimal integration of the two modalities, such as the one carried out in Boston, are clearly necessary.

648 Background: There is strong interest in testing lifestyle interventions to improve cancer outcomes, however, the optimal methods for achieving behaviour change in large scale pragmatic trials are unknown. We report the 1 year feasibility results for behaviour change in NCIC CTG CO.21 Colon Health and Life-Long Exercise Change (CHALLENGE) Trial. Methods: Between 2009 and 2014, 273 high risk stage II and III colon cancer survivors who had recently completed chemotherapy at 50 centers in Canada and Australia were randomized to a structured exercise program (SEP n = 136) or health education materials (HEM n = 137). The primary feasibility outcome in an a priordefined interim analysis was a difference between groups of ≥ 5 metabolic equivalent task (MET) hours/week in self-reported physical activity (PA) after at least 250 participants had reached 1 year. Secondary feasibility outcomes included cardiorespiratory fitness, body weight and circumferences, and objective physical functioning. Results: The SEP group reported a mean increase from baseline to 1 year PA of 15.6 MET hours/week vs a mean increase of 5.1 in the HEM group (+10.5 hrs/wk [95% CI = +3.1 to +17.9]; p = 0.002). SEP also improved relative to HEM in mean differences for predicted VO2max (+2.2ml/kg/min; p = 0.068), 6 minute walk (+29m; p < 0.001), 30 second chair stand (+1.6reps; p < 0.001), 8 foot up and go (-0.4s; p = 0.004), and the sit and reach (+2.1cm; p = 0.08). Conclusions: The behaviour change intervention in the CO.21 Trial produced an increase in self-reported PA that exceeded the feasibility criterion for trial continuation, resulted in objective fitness improvements, and is consistent with the amount of PA associated with improved colorectal cancer outcomes in observational studies. Recruitment to CO.21 remains ongoing. Clinical trial information: NCT00819208.

Chemotherapy can cure some cancers, but it has many adverse effects which can affect any system of

Chemotherapy can cure some cancers, but it has many adverse effects which can affect any system of

Aims We examined follicular lymphoma (FL) bone marrow (BM) involvement: frequency of low extent involvement, comparison of direct area measurement and a descriptive grading system and flow cytometry performance. We also assessed clinical predictors and clinical impact of FL BM status. Methods 151 consecutive initial staging BM biopsies were reviewed. Area assessment used digital photomicrography of one biopsy level and outlining intertrabecular spaces and FL infiltrates (AxioVision 7.4). A descriptive grading system proposed by Groupe d’Etudes Lymphomes Folliculaires (GELF) was applied. Results 63/151 (42%) BM were positive. Area measurement in 34 positive biopsies found area Discussion Low extent BM involvement is common in FL, without consensus guidelines for staging purposes. This has implications for the individual (stage, prognostic risk) and in clinical trial interpretation (population risk, complete response rate). The prognostic significance of low extent involvement for rituximab treated cohorts is unknown. The descriptive GELF grade, validated in this series, provides a reproducible tool suitable for prospectively addressing this question.

Background: Febrile neutropenia occurring in patients receiving chemotherapy for solid tumours or lymphoma is usually of short duration, and therefore may have a better outcome compared to patients with acute leukaemia or patients receiving myeloablative chemotherapy. Aims: To review retrospectively the outcomes for febrile neutropenia occurring in patients of the Medical Oncology Unit at out institution, and to identify factors associated with worse outcome, particularly prolonged admission or death. Methods: We reviewed 102 episodes of febrile neutropenia occurring in 85 patients treated between 1992 and 1994. Demographic factors, tumour-related factors and clinical aspects of the episodes were correlated with outcome. Results: The median age was 60 years (range, 18-87), with 56 (55%) episodes occurring in females. Twenty-eight (27%) episodes occurred in patients with lymphoma, with the remaining 74 (73%) occurring in patients with solid tumours. At presentation, the median absolute neutrophil count (ANC) was 0.14 X 10 9 /L with a median duration of significant neutropenia (ANC

9602 Background: Cancer survivors experience a range of post-treatment issues which are not well met by current services. This study explores the unmet needs of adult cancer survivors and their levels of comfort in addressing issues with oncologists and GPs. Methods: A cross-sectional survey was mailed to adult cancer survivors 4 years from diagnosis from 6 oncology units. Self-report data were obtained ranking physical, psychological and practical areas of importance to survivors; unmet needs in these areas; and the providers with whom they were happy to discuss each issue. Descriptive statistics were obtained regarding needs and preferences. Univariate and multivariate logistic regression analyses assessed demographic and clinical variables associated with 4 or more unmet care needs. Results: 228 surveys were returned (response rate 50.5%). Respondents had a mean age of 59.3 years (range 32-87), 71.5% were female, with most common primary cancers being breast (71.5%), colorectal (13.9%), prostate (4.5%) and ovarian (2.2%). The most commonly reported unmet needs were information about late effects (50.3%), managing fatigue (41.7 %), genetic risk to family (34.7%), reassurance (32.0 %) and diet (31.4 %). The median number of unmet needs was 4 (range 0-23). On univariate analysis, female gender, younger age and tertiary education were associated with greater unmet needs (p

PURPOSE: To establish the toxicity profile of simultaneously administered postoperative radiation therapy and CMF chemotherapy as a prelude to a randomized controlled study addressing the sequencing of the two modalities. METHODS AND MATERIALS: One hundred and thirty eight breast cancer patients at high risk of locoregional, as well as systemic relapse, who were referred to three centers in Australia and New Zealand were treated with postoperative radiation therapy and chemotherapy simultaneously. Acute toxicity and dose modifications in these patients were compared with 83 patients treated over the same time frame with chemotherapy alone. In a separate study the long-term radiation and surgical effects in 24 patients treated simultaneously with radiation therapy and chemotherapy at Newcastle (Australia) following conservative surgery were compared with 23 matched patients treated at Newcastle with radiation therapy alone. RESULTS: Myelotoxicity was increased in patients treated simultaneously with radiation therapy and chemotherapy. The effect was not great, but may have contributed to chemotherapy dose reductions. Lymphopenia was observed to be the largest factor in total white cell depressions caused by the simultaneous administration of radiation therapy. Postsurgical appearances were found to so dominate long-term treatment effects on the treated breast that the effect of radiation therapy dose and additional chemotherapy was difficult to detect. CONCLUSION: Studies addressing the sequencing of radiation therapy and chemotherapy will necessarily be large because adverse effects from administering the two modalities simultaneously are not great. The present study has endorsed the importance in future studies of stratification according to the extent and type of surgery and adherence to a single strict policy of chemotherapy dose modification.

3572 Notice of Retraction: "Analysis of plasma biomarkers potentially associated with antiangiogenic resistance in NCIC CTG/AGITG CO.20: A phase III randomized trial of cetuximab (CET) plus either brivanib alaninate (BRIV) or placebo in patients (pts) with chemotherapy refractory, k-RAS wild-type (WT), metastatic colorectal carcinoma (mCRC)." Abstract 3572, published in the 2012 Annual Meeting Proceedings Part I, a supplement to the Journal of Clinical Oncology, has been retracted by Jeremy Shapiro, MBBS, and Lillian Siu, MD, on behalf of the NCIC, AGITG, and all authors of the abstract. The authors have been unable to finalize their data presentation due to the complexity of the analysis, and difficulties with the statistical interpretation of the significance of several possible predictive biomarkers. Background: In the CO.20 trial, the addition of BRIV, a tyrosine kinase inhibitor targeting vascular endothelial and fibroblast growth factor receptors (VEGFR2,3 and FGFR 1,2,3), to CET, increased objective response rate and progression free survival, but did not significantly increase overall survival. Previous clinical studies demonstrated modulation of circulating angiogenic factors (CAF) in CRC which occur on therapy or upon progression (Kopetz JCO 2010). Methods: CO.20 pts were randomized 1:1 to CET plus either BRIV (Arm A) or placebo (ARM B) in a double-blind design. Pts may have had 1 prior anti-VEGF based therapy, but no prior anti-EGFR therapy. Primary endpoint was overall survival (OS). Baseline pre-treatment plasma samples were analyzed using commercial Multi-Analyte ELISAs to measure CAF, immunologic, and growth factors, with an initial discovery and subsequent validation data set. Results: 750 pts were randomized (376 in Arm A and 374 in Arm B). Median OS in the intent-to-treat population was 8.8 months in Arm A and 8.1 months in Arm B, hazard ratio (HR)=0.88; 95%CI=0.74-1.03; p=0.12. In an exploratory subgroup analysis, there is a statistically non-significant trend favoring the effect of brivanib on OS among the 41% pts who received prior anti-VEGF therapy versus those who did not.Baseline plasma samples were collected from 96% of pts, and analysis is ongoing. Results of the largest circulating biomarker analysis will be presented. CAF results will be compared with response and survival data to look for potential patient subgroups that may benefit more from the combination treatment. Conclusions: This large scale analysis will provide insights on the potential use of CAF or CAF profiles as predictive markers in CRC.

e14166 Background: Bevacizumab (Bev) induced hypertension (HTN) may be a predictive biomarker of anti-tumor activity in patients with metastatic colorectal cancer (mCRC) . We retrospectively assessed if significant rise in blood pressure (SRBP) [ ≥ 20 mmHg ] or any grade of HTN within first 10 weeks of treatment with bev is associated with improved clinical outcomes. Methods: Retrospective review of all mCRC patients, on or off clinical trial, treated with first line chemotherapy plus Bev (5 mg/kg Q2W or 7.5 mg/kg Q3W) at our institution from 2005-2010 was conducted .BP was measured before each treatment and graded according to CTCAE version 3.0.The median follow-up time of eligible patients was 19.6 months. Results: Of 50 patients eligible for the analysis, 20 patients (40%) developed significant rise in BP or HTN (SRH) whereas 30 patients had no change (NRH). There were no statistical differences between the two groups with respect to age, gender, ECOG status, number of sites of metastases, pre-existing HTN (55% SRH,37% NRH ; P=0.251) and first line chemotherapy regimen. Chemotherapy regimens used in SRH and NRH groups were 5-Fluoropyrimidine based (25% vs 23.3%), irinotecan based (40% vs. 36.7%) and oxaliplatin based (35% vs 30%). Four patients (20%) in the SRH group developed SRBP and other patients in this group developed G1-G3 HTN according to CTCAE v3.0.SRH group had improved median progression free survival (15.8 vs 6.2 months ; p

Combined modality treatment for cancer of the rectum has been shown to reduce recurrences and improve overall survival. We wished to find out if we could safely give concurrent radiotherapy and 5-fluorouracil (5-FU) modulated by leucovorin (LV) in 3 settings: pre-operatively, adjuvantly and in recurrent disease. A total of 39 patients were treated, 11 preoperatively, 17 adjuvantly and 11 with recurrent disease. There were 26 males and 13 females with a median age of 64 years. The median radiotherapy (RT) dose was 45 Gy/25 fractions/1.8 Gy per fraction (range 25-63 Gy). Chemotherapy consisted of LV 80 mg/m2 i.v. infusion over 1.5 hours followed by 5-FU 400 mg/m2 i.v. bolus, both given once a week. The median number of cycles was 8 (range 3-12). Diarrhoea was the main toxicity, and was encountered in 30 patients (77%): grade 1 in 3 (8%), grade 2 in 12 (30%), grade 3 in 11 (28%), and grade 4 in 4 (10%). This required 18 (46%) patients to have modifications to their RT (20% had breaks and 26% ceased at doses45 Gy). Nine patients (23%) had modifications in the chemotherapy (10% had breaks and 13% received6 cycles). Encouraging responses were seen in the preoperative setting. Concurrent RT and 5-FU/LV, as given in this schedule, results in an unacceptable incidence of diarrhoea, limiting both the total dose of RT and chemotherapy that can be delivered, particularly in patients who have had previous surgery.

A 56-year-old female underwent treatment with leucovorin and 5-fluorouracil for extensive metastatic moderately differentiated transitional cell carcinoma (TCC) of the renal pelvis. This resulted in a complete response for 20 + months. This combination has not been reported before in TCCs of the urinary tract and requires further exploration. (Aust NZ J Med 1991; 21: 244–245.)