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Background: Trimodality therapy using the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) trial protocol is an accepted standard of care for locally advanced oesophageal and gastroesophageal junction cancers. For medically inoperable patients, chemoradiotherapy (CRT) has been a therapeutic option., Aims: This single institution review aimed to assess the real-world application of the CROSS trial protocol., Methods: This is a retrospective review of 83 patients who underwent CRT with carboplatin and paclitaxel with trimodality or definitive intent between June 2012 and June 2018. Sixty-five patients underwent neoadjuvant CRT (NCRT); 40 had surgery, 18 had definitive CRT (DCRT). Patients' demographics, clinical, pathological, treatment and surgical characteristics were assessed. The data were analysed in exploratory analyses and Kaplan-Meier curves., Results: For 83 patients, the following median values were seen: radiotherapy dose, 50.4 Gy; chemotherapy doses, 5; and time from CRT to surgery, 62 days. Twenty-three percent NCRT and 72% DCRT patients were aged ≥75 years, and 49% and 33% of these respectively had no interruptions to CRT. Patients aged ≥75 years were more likely to have DCRT (P = 0.001). Patients who underwent surgery were younger (P = 0.04). For NCRT and surgery, NCRT only and DCRT respectively, median overall survival was 35.5, 12.1 and 17.1 months (log rank P = 0.008); progression-free survival was 32.2, 10 and 9.6 months (log rank P = 0.001)., Conclusions: Despite broadening of the CROSS trial eligibility criteria in our real-world data, there appears to be a survival benefit with trimodality therapy. The use of carboplatin and paclitaxel in DCRT may be of value and requires further study., (© 2021 Royal Australasian College of Physicians.)

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference was held in Halifax, Nova Scotia, 20-22 September 2018. Experts in radiation oncology, medical oncology, surgical oncology, and pathology who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of pancreatic cancer, pancreatic neuroendocrine tumours, hepatocellular cancer, and rectal and colon cancer, including ■ surgical management of pancreatic adenocarcinoma,■ adjuvant and metastatic systemic therapy options in pancreatic adenocarcinoma,■ the role of radiotherapy in the management of pancreatic adenocarcinoma,■ systemic therapy in pancreatic neuroendocrine tumours,■ updates in systemic therapy for patients with advanced hepatocellular carcinoma,■ optimum duration of adjuvant systemic therapy for colorectal cancer, and■ sequence of therapy in oligometastatic colorectal cancer., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conf licts of interest, and we declare the following interests: DA is a member of advisory boards for Bristol–Myers Squibb, Sanofi, and Shire, and has received grants or honoraria from Celgene and Amgen; TA is a member of advisory boards for Amgen, Apobiologix, Bayer, Eisai, Novartis, Ipsen, Celgene, and Shire, and has received grants or honoraria from Novartis and Ipsen; SB (Berry) is a member of advisory boards for Amgen, Bayer, Servier, and Taiho, and has received grants or honoraria from Amgen; DB has received grants or honoraria from Amgen, AbbVie, AstraZeneca, Bristol–Myers Squibb, Ipsen, and Pfizer; BC is a member of advisory boards for Amgen, Eli Lilly, Taiho, Shire, Celgene, Merck, and Novartis; EC is a member of advisory boards for Taiho and Eisai, and is listed as co-investigator for trials at an institution that has received funding from AstraZeneca, Bristol–Myers Squibb, Boston Biomedical, Merck, and Seattle Genetics; RG (Goodwin) is a member of advisory boards for Ipsen, Novartis, Taiho, and Celgene, and has received funding from Novartis, Ipson, and Pfizer in an unrestricted grant for a tumour bank; SG is a member of advisory boards for Amgen, Ipsen, Merck, Pfizer, and Sanofi, and has received funding from Janssen and Sanofi as honoraria for a talk; PK is a member of advisory boards for Sanofi and is listed as a co-investigator for trials at an institution that has received for grants or honoraria from Baxter and Sanofi; NL is a member of advisory boards for Amgen, Celgene, Genomic Health, Bristol–Myers Squibb, Novartis, and Eisai, and is a member of speaker’s bureaus for Amgen, AstraZeneca, Astellas, Roche, Eisai, Novartis, Celgene, and Bristol–Myers Squibb; JM is a member of advisory boards for Amgen and has received grants or honoraria from Bristol–Myers Squibb for a talk; EP is a member of advisory boards for Amgen and Pfizer and has received grants or honoraria from Roche for travel to a symposium; RR is a member of advisory boards for Celgene, Servier, Eisai, Merck, Bayer, and Eli Lilly, is a member of the speaker’s bureaus for Celgene, Servier, Novartis, and Eli Lilly, and is listed as co-investigator for trials at an institution that has received funding from Merck, Bristol–Myers Squibb, AstraZeneca, and Macrogenetics, and has received grants or honoraria from Essai and Celgene; WS has received grants or honoraria from Genomic Health for a conference presentation; SS is a member of advisory boards for AstraZeneca, Boehringer Ingelheim, Bristol–Myers Squibb, Merck, Roche, Novartis, Shire, Amgen, and Lilly, is listed as coinvestigator for trials at an institution that has received funding from Bristol–Myers Squibb, Novartis, Merck, and AbbVie, and has received grants or honoraria from Amgen and Taiho for travel; MT (Tehfé) is a member of advisory boards for Bristol–Myers Squibb, AstraZeneca, Merck, Eisai, Takeda Celgene, and Taiho, and has received grants or honoraria from Celgene for research; MT (Thirlwell) is a member of an advisory board for Taiho; KV is a member of an advisory board for Amgen and has received grants or honoraria from Roche for travel to European Society for Medical Oncology meetings; SW is a member of an advisory board for Amgen and has received grants or honoraria from Amgen and Ipsen for invited talks. The remaining authors have no conflicts to disclose., (2019 Multimed Inc.)

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2017 was held in St. John's, Newfoundland and Labrador, 28-30 September. Experts in radiation oncology, medical oncology, surgical oncology, and cancer genetics who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of gastric, rectal, and colon cancer, including ■ identification and management of hereditary gastric and colorectal cancer (crc);■ palliative systemic therapy for metastatic gastric cancer;■ optimum duration of preoperative radiation in rectal cancer-that is, short- compared with long-course radiation;■ management options for peritoneal carcinomatosis in crc;■ implications of tumour location for treatment and prognosis in crc; and■ new molecular markers in crc.

Background: Immune-modulating drugs have recently been introduced to the second-line setting of advanced bladder cancer. Pembrolizumab increases overall survival and is associated with less toxicity compared with chemotherapy in this setting based on the Keynote 045 study. The high cost of immunotherapy necessitates an assessment of its value by considering both efficacy and cost., Objective: To estimate the cost-effectiveness of pembrolizumab for the second-line treatment of advanced bladder cancer from the perspective of payers in multiple countries., Design, Setting, and Participants: We developed a Markov model to compare the cost and effectiveness of pembrolizumab with those of chemotherapy in the second-line treatment of advanced bladder cancer based on the Keynote 045 study. Drug costs were acquired for the United States (US), United Kingdom (UK), Canada, and Australia. All costs were converted from local currency to US dollars at the exchange rates in September 2017., Outcome Measurements and Statistical Analysis: Health outcomes were measured in quality-adjusted life-years (QALYs)., Results and Limitations: Pembrolizumab generated a gain of 0.36-0.37 QALYs compared with chemotherapy. Our analysis established the following incremental cost-effectiveness ratios (ICERs) for pembrolizumab versus chemotherapy in second-line advanced bladder cancer treatment: US $122 557/QALY; UK $91 995/QALY; Canada $90 099/QALY; and Australia $99 966/QALY. The willingness-to-pay (WTP) thresholds per QALY are considered to be around 100 000-150 000 US dollars for the US, 20 000-50 000 pounds for the UK (US$25 000-65 000), 20 000-100 000 CAD for Canada (US$16 000-80 000), and 40 000-75 000 AUD for Australia (US$32 000-60 000)., Conclusions: Cost-effectiveness and WTP thresholds vary between countries. Compared with the other countries examined, US drug prices were found to be the highest, leading to the highest ICER. With standard WTP thresholds, pembrolizumab may be considered cost-effective in the US but not in the other countries examined., Patient Summary: This article assessed the cost-effectiveness of pembrolizumab for the treatment of patients with metastatic bladder cancer who had previously failed one treatment regimen. It would cost $122 557 in the United States, $91 995 in the United Kingdom, $90 099 in Canada, and $99 966 in Australia to gain one quality-adjusted life-year with pembrolizumab versus chemotherapy in these patients, which may be considered cost-effective only in the United States because of the differences in willingness-to-pay thresholds., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: In the U.S., the addition of bevacizumab to first-line chemotherapy in metastatic colorectal cancer (mCRC) has been demonstrated to provide 0.10 quality-adjusted life years (QALYs) at an incremental cost-effectiveness ratio (ICER) of $571,000/QALY. Due to variability in pricing, value for money may be different in other countries. Our objective was to establish the cost-effectiveness of bevacizumab in mCRC in the U.S., U.K., Canada, Australia, and Israel., Methods: We performed the analysis using a previously established Markov model for mCRC. Input data for efficacy, adverse events, and quality of life were considered to be generalizable and therefore identical for all countries. We used country-specific prices for medications, administration, and other health service costs. All costs were converted from local currency to U.S. dollars at the exchange rates in March 2016. We conducted one-way and probabilistic sensitivity analyses (PSA) to assess the model robustness across parameter uncertainties., Results: Base case results demonstrated that the highest ICER was in the U.S. ($571,000/QALY) and the lowest was in Australia ($277,000/QALY). In Canada, the U.K., and Israel, ICERs ranged between $351,000 and $358,000 per QALY. PSA demonstrated 0% likelihood of bevacizumab being cost-effective in any country at a willingness to pay threshold of $150,000 per QALY., Conclusion: The addition of bevacizumab to first-line chemotherapy for mCRC consistently fails to be cost-effective in all five countries. There are large differences in cost-effectiveness between countries. This study provides a framework for analyzing the value of a cancer drug from the perspectives of multiple international payers., Implications for Practice: The cost-effectiveness of bevacizumab varies significantly between multiple countries. By conventional thresholds, bevacizumab is not cost-effective in metastatic colon cancer in the U.S., the U.K., Australia, Canada, and Israel., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2017.)

Purpose: Aflibercept is a recombinant fusion protein of the VEGF receptor (VEGFR) 1 and VEGFR2 extracellular domains. We assessed the safety and efficacy of aflibercept in patients with metastatic colorectal cancer (MCRC) who had received at least one prior palliative regimen., Experimental Design: Seventy-five patients were enrolled onto this two-stage phase II trial in two cohorts, bevacizumab naïve (n = 24) and prior bevacizumab (n = 51). Aflibercept was administered at 4 mg/kg i.v. in two-week cycles. The primary endpoint was a combination of objective response rate and 16-week progression-free survival (PFS)., Results: In the bevacizumab-naïve cohort (n = 24), the best response was stable disease for 16 weeks or more in five of 24 patients. In the prior bevacizumab cohort (n = 50), one patient achieved a partial response and six patients had stable disease for 16 weeks or more. The median PFS in the bevacizumab-naïve and prior bevacizumab cohorts was two months [95% confidence interval (CI): 1.7-8.6 months] and 2.4 months (95% CI: 1.9-3.7 months), respectively. Median overall survival (OS) was 10.4 months (95% CI: 7.6-15.5) and 8.5 months (95% CI: 6.2-10.6), respectively. The most common grade 3 or higher treatment-related adverse events were hypertension, proteinuria, fatigue, and headache. Ten patients discontinued study treatment due to toxicity. Mean free to VEGF-bound aflibercept ratio was 1.82, suggesting that free aflibercept was present in sufficient amount to bind endogenous VEGF., Conclusion: Aflibercept showed limited single-agent activity in patients with pretreated MCRC with moderate toxicity. Further study of aflibercept with chemotherapy is ongoing., (©2012 AACR.)

Introduction: Adjuvant chemotherapy in non-small cell lung cancer (NSCLC) has become a new standard of care. This study examines the uptake patterns for adjuvant chemotherapy outside of clinical trials., Methods: A retrospective study of all patients diagnosed with NSCLC in the year 2005 who underwent curative-intent surgery in Nova Scotia, Canada was conducted. Logistic regression models and discriminant function analyses were employed to identify cofactors associated with referral to medical oncology and/or utilization of adjuvant chemotherapy., Results: Of 540 patients with NSCLC, 108 underwent curative-intent surgery (67% lobectomy; 15% pneumonectomy; 19% wedge resection) for NSCLC (39% IA; 24% IB; 25% II; 14% III). Referral to medical oncology was observed in 44% (47 of 108) of all patients including 73% (30 of 41) of those with stage II-III. Adjuvant chemotherapy utilization was observed in 62% (29 of 47) of those referred including 73% (22 of 30) of those with stage II-III. Overall, 27% (29 of 108) of all patients received adjuvant chemotherapy, including 54% (22 of 41) of those with stage II-III. Higher uptake was significantly associated with age (younger versus older), stage (II/III versus I), and surgery type (pneumonectomy versus wedge). Weaker associations were observed with other cofactors including surgeon, health center, mean household income, and surgery-medical oncologist consult timeline., Conclusions: The uptake of adjuvant chemotherapy in patients with resected NSCLC outside of clinical trials is low overall, but is higher among younger patients and those with more advanced stages. These uptake patterns may allow future planning of health resource utilization and/or improvement of chemotherapy utilization rates.

Introduction: Wait times in cancer care continue to be an important clinical, social, and political issue. This study examines wait times along the care path from suspicious imaging study (Detection) to adjuvant chemotherapy initiation (Chemotherapy) for patients with early-stage non-small cell lung cancer (NSCLC) who undergo surgical resection., Methods: A retrospective chart review of patients diagnosed in 2005 with NSCLC who underwent curative-intent surgery in Nova Scotia, Canada was conducted to abstract dates of care events (Detection, Surgery Consultation, Surgery, Medical Oncology [MO] Referral, MO Consultation and Chemotherapy) and patient characteristics. Multifactorial regression methods were used to identify statistically-significant cofactors associated with wait times at various resolutions of care intervals (low, intermediate, high)., Results: A median wait time of 141 days elapsed between Detection-Chemotherapy; and a median 107 and 52 days elapsed between Detection-Surgery and Surgery-Chemotherapy, respectively. A number of demographic, clinical, epidemiological, and system resource dependant factors influenced wait times at different resolutions, and were best detailed utilizing high resolution analysis. Wait time between MO referral-MO Consultation was inversely related to that experienced in the preceding interval of Surgery-MO Referral., Conclusions: This study provides a first detailed examination of wait times experienced by NSCLC patients undergoing curative-intent surgery according to care interval definitions; demonstrates the value of high care interval resolution analysis to detect bottlenecks in access to care; and reports on the interdependence of elapsed times between care events along the care path for cancer patients.

Objective: Monoclonal antibodies (MAbs) such as trastuzumab and bevacizumab have become important yet expensive components of systemic cancer therapy across a variety of disease sites. We assessed the potential cost implications of adopting trastuzumab and bevacizumab therapy in the context of their potential utilization in breast, lung, and colorectal cancers., Design: We first estimated MAb costs per patient and treatment indication and then included the MAb acquisition cost and the costs of medical resource utilizations required for therapy delivery. Drug costs were based on 2005 average Canadian wholesale prices, assuming full drug delivery and uncomplicated cycles. A direct-payer perspective was undertaken, and results are reported in Canadian dollars. Potential lifetime costs were then derived according to constructed schema, which account for absolute numbers of target patients and systemic therapy utilization. We subsequently estimated costs of MAb therapy relative to total costs of conventional management without MAb therapy., Results: Trastuzumab costs $49,915 and $28,350 per patient treated in the adjuvant and metastatic breast cancer settings, respectively; bevacizumab costs $48,490 and $39,614 per patient treated in the metastatic lung and colorectal cancer settings, respectively. Potential lifetime absolute costs to Canada's health care system were approximately $127 million and $299 million for trastuzumab and bevacizumab respectively, corresponding to an average increase in health care expenditure of approximately 19% for breast cancer and 21% for lung and colorectal cancer over conventional management without MAbs., Conclusions: Novel Mab-based therapies such as trastuzumab and bevacizumab will likely add a significant cost burden to Canada's publicly funded health care system.

Objective: To systematically review the accuracy of physicians' clinical predictions of survival in terminally ill cancer patients., Data Sources: Cochrane Library, Medline (1996-2000), Embase, Current Contents, and Cancerlit databases as well as hand searching., Study Selection: Studies were included if a physician's temporal clinical prediction of survival (CPS) and the actual survival (AS) for terminally ill cancer patients were available for statistical analysis. Study quality was assessed by using a critical appraisal tool produced by the local health authority., Data Synthesis: Raw data were pooled and analysed with regression and other multivariate techniques., Results: 17 published studies were identified; 12 met the inclusion criteria, and 8 were evaluable, providing 1563 individual prediction-survival dyads. CPS was generally overoptimistic (median CPS 42 days, median AS 29 days); it was correct to within one week in 25% of cases and overestimated survival by at least four weeks in 27%. The longer the CPS the greater the variability in AS. Although agreement between CPS and AS was poor (weighted kappa 0.36), the two were highly significantly associated after log transformation (Spearman rank correlation 0.60, P < 0.001). Consideration of performance status, symptoms, and use of steroids improved the accuracy of the CPS, although the additional value was small. Heterogeneity of the studies' results precluded a comprehensive meta-analysis., Conclusions: Although clinicians consistently overestimate survival, their predictions are highly correlated with actual survival; the predictions have discriminatory ability even if they are miscalibrated. Clinicians caring for patients with terminal cancer need to be aware of their tendency to overestimate survival, as it may affect patients' prospects for achieving a good death. Accurate prognostication models incorporating clinical prediction of survival are needed.

A request for euthanasia (RFE) in the terminally ill raises concerns that physical and/or mental suffering remain unaddressed and thus mandates a critical appraisal of the physical and psychosocial aspects of the individual concerned. An alert datasheet (AD) is completed at the weekly Palliative Care Service (PCS) meeting as a measure of self-audit and deals with issues considered to be of importance in ensuring high-quality patient care, one of which is a RFE. The ADs for the year 2000 were examined, and where a RFE was made, the contributing factors as documented on the forms together with demographic data, the case synopsis and patient-rated main three problems/issues were appraised. Among 490 patients referred to the service, there were 6 RFE (1.6%) recorded. These were made by 1 female (age 44) and 5 male (age range 58-78 years) patients. Four of these patients had a cancer diagnosis (all had metastatic disease). Median survival from first contact with the PCS was 13 days (range 4-29). The contributing factors identified were: uncontrolled symptoms (2/6 - severe constipation in both), depression (1/6), issues of burden/dependency (6/6), lack of autonomy/control (4/6), sense of hopelessness (3/6) and social isolation (4/6). The patient-rated main three problems were: (i) physical symptoms (5/6), specifically pain (2/6), shortness of breath (2/6), fatigue (1/6) and nausea (1/6), and (ii) psychosocial issues (4/6). A RFE was seen to be a multifactorial entity (issues of burden/dependency being universal) and merits a focused appraisal in order to adequately address potentially unrecognised issues that contribute to suffering. The short median survival from the time of referral to the service suggests that (i) RFEs are made late in the trajectory of the illness and (ii) these patients are being referred late in the course of their illness - thus limiting the window in which these issues can be addressed.

Most malignancies are characterised by malignant behaviour at some point in the disease trajectory. However, non-malignant diseases may exhibit malignant behaviour. A diagnosis of malignancy based on fine needle aspiration cytology (FNAC) can be misleading. We report a case of Wegener's granulomatosis initially diagnosed by FNAC as adenocarcinoma of unknown primary. The limitations of FNAC, the disparate prognoses of the two diagnoses despite a compatible clinical picture and the need for clinical vigilance in monitoring a disease course are highlighted.

The role of a Palliative Medicine Liaison Consultation Service (LCS) in a large tertiary referral teaching hospital was examined by the prospective evaluation of 50 cases consecutively referred, together with the subsequent advice/recommendations (4 categories: pharmacological, non-pharmacological, clarification of goal of treatment, care system upon discharge) given during the consultation. The utility of a simple scoring system in quantifying the impact (4 grades: deleterious, no effect, positive, very positive) of the advice given on individual patient outcome, scored by both the referring team and the LCS, was studied. Eighty percent of cases had a cancer diagnosis. Pain was the most common symptom (50% cases) and "pain control" the most common referral reason cited. The median number of recommendations per patient was 3.0 and the majority (70%) concerned symptom control recommendations. Advice was given regarding discharge planning in nearly two-thirds of cases and such advice dealing with the care system upon discharge was judged by the referring team to have the highest positive impact of all recommendations. Nearly three-fourths of cases (74%) were graded by the referring team as having at least one recommendation with a positive impact. The simple scoring system used is demonstrably a useful outcome assessment tool. The LCS is perceived to have a positive impact on patient care in an acute hospital setting and appears to fill a gap in the multi-specialty provision of care.

The increasing duration of life from disease diagnosis to death in cancer and chronic non-malignant illnesses argues for a revised approach to end-of-life care that incorporates the principles of palliative care from an earlier stage (ie, a stage at which curative and/or life-prolonging treatments are still being provided). The provision of active treatment and comfort measures/death preparation in parallel has been called the "mixed management model" of end-of life care.

The aim of this prospective study was to validate the Palliative Prognostic (PaP) Score in a population of hospitalized patients in Australia in order to determine its applicability in a different setting to that in which it was originally developed. Individual PaP scores were calculated for 100 terminally-ill patients consecutively referred to a palliative medicine consultation service based in a university teaching hospital. The PaP score was able to subdivide this heterogeneous patient population into three groups, the differences being highly statistically significant. Median survivals for the three groups were, respectively, 60 days (95% confidence interval 41-89 days), 34 days (25-40), and 8 days (2-11). The percentage survival at 30 days for the three groups was 66%, 54%, and 5% respectively. These data suggest that the PaP scoring system is a reasonably robust method for prognostication in advanced cancer that appears to be independent of the setting. The short survival of the third group in this study, which is consistent with the presence of a subset of gravely ill patients within the hospital setting who are referred to specialist palliative care services very late in the course of their illness, raises important issues for the care and treatment of these individuals.

The role of antiemetics is invaluable in allowing cancer patients to complete otherwise potentially intolerable chemotherapy. Corticosteroids have an established place in the prevention and treatment of nausea and vomiting due to emetogenic cytotoxic agents. Avascular necrosis of bone is a recognised complication of glucocorticoid treatment--the risk of this increasing with higher doses and longer duration of use. This report details a case of bilateral avascular necrosis of the femoral heads in a patient receiving 'standard' doses of dexamethasone as part of the antiemetic regimen used in cisplatin-based combination chemotherapy.

The cytotoxic regimen of epirubicin, cisplatin, and continuous infusional 5-fluorouracil (ECF) has demonstrated activity in a range of malignancies, including gastroesophageal, breast, and pancreatic cancers. Prolonged infusional central venous catheter (CVC) mediated therapy is not always feasible and modifications of the 5-fluorouracil (5FU) schedule have been reported. We reviewed our experience of both the standard and a modified ECF regimen in patients diagnosed with carcinoma of unknown primary site (CUPS). A retrospective analysis of all patients diagnosed with CUPS (31 adenocarcinoma and 5 poorly differentiated carcinoma) and treated with ECF between June 1994 and June 1998 was undertaken. Thirty-six patients, median age 56 (range: 24-74), were treated thrice-weekly with 50 mg/m2 epirubicin, 60 mg/m2 cisplatin, and 5-FU administered either by continuous infusion 200 mg/m2/d via a CVC (standard ECF) or as a 6-h infusion 600 mg/m2 through a peripheral venous catheter (modified ECF). Thirteen patients were treated with standard ECF and 23 received modified ECF. The median number of cycles administered was 4 (range: 1-10). Thirty-two patients had evaluable disease, seven (22%; 95% confidence interval: 8-36%) demonstrated a partial response, including three patients that received standard ECF and four treated with modified ECF. There were no complete responses. The median survival for all 36 patients was 9.0 mo. Median survival for patients treated with standard ECF was 11.7 mo as compared to 5.1 mo for the modified ECF schedule (p = 0.052). Liver involvement and elevation of serum CA19.9 were identified as possible adverse prognostic factors. Both regimens were well tolerated, with the only grade 3/4 toxicity recorded being leukopenia (four patients), nausea/vomiting (seven patients), and diarrhea (one patient). CVC complications in the standard ECF group were thrombosis (one patient) and infection (three patients). There were no treatment-related deaths. We conclude that ECF, whether modified or standard, has modest activity in the setting of CUPS. Patient survival is comparable to survival documented in previous reports of CUPS treatment. The apparent survival difference between the two ECF schedules may be the result of patient selection factors. The optimal treatment of CUPS remains unknown and can only be determined through randomized controlled trials.

Background: Although morphine is the mainstay of pharmacological therapy in cancer pain, it remains feared and suboptimally used. Different formulations and the advent of 'new' opioids facilitate the attainment of pain control., Objective: To clarify the current role of various opioids including morphine in the management of cancer pain. To provide a practical framework to guide 'best practice' opioid use in a general practice setting., Discussion: The optimal application of opioids is governed by their clinical pharmacology and hindered by unfounded fears and misunderstanding. Different formulations within different types of opioids augment a favourable balance in the pain relief versus adverse effects equation and used within a four point approach, should serve to deliver optimal pain control.

Background: Cancer pain remains significantly undertreated despite being one of the most prevalent and feared symptoms associated with cancer. Approximately 90% of patients can have their cancer pain controlled through relatively simple measures., Objective: The aim of this review is to facilitate the current optimal approach to the assessment and management of cancer pain within the context of the multidimensional nature of the pain experience., Discussion: Each component of the pain experience is addressed using a four point approach to pain and involves pharmacological and nonpharmacological measures. The general practitioner's role is pivotal in optimal cancer pain management. This is the first of two articles by Kiran Virik and Paul Clare on pain management in palliative care. The second, outlining treatment options, will appear in the December issue of Australian Family Physician.

Craniopharyngioma is a well recognised intracranial tumour; malignant transformation has been rarely described. In that case, malignant change occurred following irradiation for local recurrence and information is not provided on the biological behaviour of the tumour or the response to management. We report a further case of malignant transformation in recurrent craniopharyngioma following radiotherapy. The biological behaviour of malignant change in craniopharyngioma is uncertain so the treatment modalities require consideration of toxicity and other adverse sequelae balanced against anticipated outcome and comorbidities from previous treatments. The pathophysiology and therapeutic strategies are discussed. We review the possible pathogenic link between radiation therapy and malignant transformation.