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ABSTRACT: A number of curricula have been developed to address shortfalls in cancer education. However, no standardised means of assessing medical graduates against such curricula currently exist. This paper describes the use of expert panels to determine the level of cancer-related knowledge required by junior doctors. Participants individually reviewed knowledge items from the Ideal Oncology Curriculum for Medical Students and rated the level of understanding and specificity of each. On completion, panel sessions were convened to reach consensus. Fifty-two (17 %) items were considered irrelevant for junior doctors, whilst 164 items (54 %) and 85 items (28 %) were deemed appropriate at a moderate and high level of understanding, respectively. As a result, 249 (83 %) of the 301 items were deemed appropriate for junior doctors. Expert panels provide an important insight into the requirements of junior doctors, reduce ambiguity and facilitate discussion, resulting in higher quality data than that produced solely through individual reviews.
Journal of Cancer Education 02/2013; · 0.76 Impact Factor
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ABSTRACT: This paper describes the sources of variability encountered in the use of an expert panel to review cancer-related knowledge items, necessary for medical students. Variability was observed in the interpretation of written material relating to the definition and rationale for the task to be completed by individual panel members, including the definition of a junior doctor, and levels of understanding and specificity. Panel sessions undertaken in phase II provided facilitated discussion and the ability to clearly define the aims and tasks required of participants, resulting in data of a higher quality. Consensus was achieved in a single session that would have likely taken several iterations of individual data collection to achieve. Eliminating phase I has the potential to remove the majority of variability encountered in this study. Subsequently, the resultant decrease in time demanded of participants would likely result in higher recruitment and participation rates.
Journal of Cancer Education 01/2013; · 0.76 Impact Factor
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ABSTRACT: There is no accepted second-line therapy for patients with advanced malignant pleural mesothelioma (MPM), whose disease has progressed after first-line chemotherapy. The multitargeted tyrosine kinase inhibitor sunitinib malate targets several pathways overexpressed in mesothelioma. This phase II study assessed objective response to sunitinib and correlative biomarkers in patients with progressive pretreated MPM.
Eligible patients had confirmed MPM, radiological progression after chemotherapy, Eastern Cooperative Oncology Group performance status 0 to 1, and measurable disease. Patients received oral sunitinib 50 mg daily for 28 of every 42 days. The primary endpoint was objective radiological response. Patients without prior pleurodesis had fluorodeoxyglucose positron emission tomographic response assessed by total glycolytic volume criteria. Correlative biomarkers included serum mesothelin, vascular endothelial growth factor (VEGF)-A, VEGF-C, interleukin-8, sVEGFR-2, sVEGFR-3, and s-kit.
Fifty-three patients received sunitinib between July 2006 and December 2009; 51 were assessable for response. Patients received a median of two cycles (range, 1-12); 40% required dose reduction. Fatigue was the most prominent toxicity. Six patients (12%) had a confirmed radiological partial response, 34 (65%) had stable disease, and 11 (22%) had progressive disease as best response. Six of 20 patients had a decrease in fluorodeoxyglucose positron emission tomographic total glycolytic volume of 15% or more. Median overall survival was 6.1 months, and median time to progression was 3.5 months. Correlative biomarkers did not predict treatment response.
Sunitinib has activity in a subset of patients with pretreated MPM. Consideration should be given to different treatment schedules and examination of other biomarkers for further study of sunitinib in MPM.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 09/2012; 7(9):1449-56. · 4.55 Impact Factor
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ABSTRACT: Cutaneous malignant melanoma is a major public health issue in Australia and other nations. A greater understanding of the genetic determinants and their interactions with environmental factors may lead to better interventions and control of the disease. The Western Australian Melanoma Health Study (WAMHS) is a population-based case-collection and biospecimen resource established to investigate the genetic epidemiology of melanoma. This manuscript discusses the design of the WAMHS and the characteristics of the participants.
Participants were recruited through the Western Australian Cancer Registry, which is notified of all incident cancers in the state of Western Australia by law. Once the diagnosing doctor's consent was obtained, all eligible, resident Western Australian, adult cases of melanoma diagnosed between January 2006 and September 2009, were contacted by mail and invited to participate. Clinical, questionnaire-based phenotypic and blood samples for extraction of DNA, RNA and serum were collected from consenting cases. Clinical data consisted of all pathological data recorded by the cancer registry and the questionnaire, administered by telephone interview, covered major risk factors for melanoma, such as sun exposure history and skin type.
The final sample consisted of 1643 consenting cases out of 3420 cancer notifications (48.04%), of which 1455 cases completed one or more components of the study and 1157 completed all components. The WAMHS sample differed to all melanoma notifications only in age, with a bias towards older individuals (P<0.0001). No significant differences were observed in sex, melanoma site, Breslow thickness or Clark's level.
The WAMHS study is novel in its non-family based approach and focus on common (low penetrance) genetic determinants. This comprehensive resource will enable further steps to be taken towards understanding the complex pathways involved in melanoma.
Cancer epidemiology. 04/2011; 35(5):423-31.
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ABSTRACT: Tasisulam sodium (hereafter, tasisulam) is a novel anticancer agent that induces apoptosis through the intrinsic pathway and has antiangiogenic activity in preclinical models. Tasisulam demonstrated activity across a broad range of tumors, including melanoma. The primary objective of this phase 2 study was to determine the objective response rate (ORR) in patients who had received 1 previous systemic chemotherapy for unresectable/metastatic melanoma; secondary objectives were to evaluate the clinical response rate (CRR), progression-free survival (PFS), overall survival (OS), duration of response, safety, and pharmacokinetics.
Tasisulam was administered intravenously on Day 1 of 21-day cycles according to a lean body weight-based dosing algorithm targeting a peak plasma concentration (C(max) ) of 420 μg/mL.
In 68 enrolled patients, the median age was 59 years (range, 26-83 years). No patients had a complete response (CR), 8 patients had a partial response (PR), and 24 patients had stable disease (SD); the ORR (CR + PR) was 11.8%, and the CRR (CR + PR + SD) was 47.1%. The median PFS was 2.6 months, and the median OS was 9.6 months. The predominant treatment-related grade 3/4 toxicity was thrombocytopenia (20.6% of patients). Tasisulam exhibited a biexponential disposition with a predicted distribution half-life of 0.3 hours to 2.8 hours and a median terminal elimination half-life of 10 days (consistent with the turnover of albumin), suggesting that tasisulam is very tightly bound to albumin.
Tasisulam administered at a targeted C(max) of 420 μg/mL on Day 1 of 21-day cycles demonstrated activity and tolerable toxicity as second-line treatment in malignant melanoma. These results led to a registration trial in metastatic melanoma. Cancer 2011;. © 2011 American Cancer Society.
Cancer 03/2011; 117(20):4732-9. · 4.77 Impact Factor
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Anna K Nowak,
Roslyn J Francis,
Michael J Phillips, Michael J Millward,
Agatha A van der Schaaf,
Jan Boucek,
Arthur W Musk,
Melanie J McCoy,
Amanda Segal,
Peter Robins,
Michael J Byrne
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ABSTRACT: Existing prognostic systems for malignant pleural mesothelioma do not incorporate imaging information. We aimed to identify the contribution of quantitative fluorodeoxyglucose positron emission tomography (FDG-PET) analysis to other prognostic variables in this disease.
Patients with malignant pleural mesothelioma underwent helical thoracoabdominal computed tomography and FDG-PET scans at baseline. Patients were treated as clinically indicated and followed for survival. FDG-PET variables derived included total glycolytic volume, a composite of tumor volume and glycolytic activity.
Ninety-three patients were accrued from 2003 to 2006. Of 89 eligible assessable patients, 28 had undergone pleurodesis before enrolment. Seventeen patients remained alive at analysis; median survival is 15.4 months. On univariate analysis, significant prognostic factors were: total glycolytic volume on FDG-PET (P = 0.003), sarcomatoid histology (P < 0.0005), weight loss (P = 0.031), computed tomography stage (P = 0.015), and European Organization for Research and Treatment of Cancer good prognostic score (P = 0.049). In patients with epithelioid or biphasic histology, baseline total glycolytic volume remained predictive of survival in patients with (P = 0.01) or without (P = 0.018) previous pleurodesis. In multivariate analysis, no variable other than histology contributed to the model in patients with sarcomatoid histology; total glycolytic volume and weight loss contributed to the models in patients with nonsarcomatoid histology. computed tomography-assessed tumor-node-metastasis stage did not contribute to the model. A nomogram, which incorporates quantitative PET parameters and pleurodesis into prognostic information, is presented.
Sarcomatoid histology remains the strongest prognostic factor. In patients with non sarcomatoid disease, volumetric FDG-PET parameters are more predictive of survival than tumor-node-metastasis staging, suggesting that tumor volume and glycolytic activity may be more important determinants of prognosis in malignant pleural mesothelioma than anatomic extent of disease.
Clinical Cancer Research 04/2010; 16(8):2409-17. · 7.74 Impact Factor
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ABSTRACT: The past decade has seen an increased effort to standardized medical curricula internationally. Despite these efforts, a lack of standardization remains evident, most likely owing to the lack of specificity with which such frameworks are often (out of necessity) constructed. As such, inconsistencies may arise owing to differences in adopted definitions and approaches to assessment. The authors highlight six key points to aid the individual educator in translating overarching frameworks into specific learning objectives that are measurable, written at a level of generality, complexity and difficulty that is clear, appropriate and explicit in what is required of the student.
Journal of Cancer Education 03/2010; 25(3):285-9. · 0.76 Impact Factor
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ABSTRACT: Oxaliplatin-induced lung disease is an increasingly recognised phenomenon. We describe here three cases of presumed oxaliplatin-induced interstitial lung disease. With increasing use of oxaliplatin for colorectal cancer, awareness of this complication and the need for early diagnosis and treatment of respiratory symptoms can lead to early cessation of chemotherapy, rapid exclusion of alternative diagnoses and initiation of treatment with corticosteroids.
Asia-Pacific Journal of Clinical Oncology 08/2008; 4(3):175 - 180. · 0.58 Impact Factor
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Karl D Lewis,
William A Robinson, Michael J Millward,
Alex Powell,
Timothy J Price,
Damien B Thomson,
Euan T Walpole,
Andrew M Haydon,
Brian R Creese,
Kaye L Roberts,
John R Zalcberg,
Rene Gonzalez
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ABSTRACT: Treatment options for advanced melanoma are limited. PI-88, a potent inhibitor of heparanase, demonstrates anitangiogenic properties and has shown activity against melanoma in phase I studies. This was an open-label, multicenter, phase II study of PI-88 in patients with advanced melanoma. Patients received a fixed-dose of 250 mg/day given subcutaneously for four consecutive days followed by three drug-free days per week in a 28-day cycle. A total of 44 patients were enrolled in the intent to treat population, with 59.1% having received previous therapy. The median time to progression and overall survival was 1.7 months and 9 months, respectively. Forty-one patients are included in the efficacy analysis. One (2.4%) patient achieved a partial response, six (14.6%) patients had stable disease as best response, and 30 (73.2%) had progressive disease. At the end of six cycles of treatment, three of the 41 evaluable patients had non-progressive disease. Treatment was generally well tolerated. Injection site bruising occurred in 45% of patients. Serious bleeding did occur in two patients and three patients developed a positive anti-platelet antibody test during the study. One of these four patients experienced an associated thrombosis. In patients with advanced melanoma, PI-88 demonstrates an overall survival and time to progression similar to standard chemotherapy. Although the current study did not meet the primary end-point of progression free survival of >or=20%, there is some evidence of activity and further investigation is warranted.
Investigational New Drugs 02/2008; 26(1):89-94. · 3.36 Impact Factor
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ABSTRACT: The aim of chemotherapy for mesothelioma is to palliate symptoms and improve survival. Measuring response using CT is challenging because of the circumferential tumor growth pattern. This study aims to evaluate the role of serial (18)F-FDG PET in the assessment of response to chemotherapy in patients with mesothelioma.
Patients were prospectively recruited and underwent both (18)F-FDG PET and conventional radiological response assessment before and after 1 cycle of chemotherapy. Quantitative volume-based (18)F-FDG PET analysis was performed to obtain the total glycolytic volume (TGV) of the tumor. Survival outcomes were measured.
Twenty-three patients were suitable for both radiological and (18)F-FDG PET analysis, of whom 20 had CT measurable disease. After 1 cycle of chemotherapy, 7 patients attained a partial response and 13 had stable disease on CT assessment by modified RECIST (Response Evaluation Criteria in Solid Tumors) criteria. In the 7 patients with radiological partial response, the median TGV on quantitative PET analysis fell to 30% of baseline (range, 11%-71%). After 1 cycle of chemotherapy, Cox regression analysis demonstrated a statistically significant relationship between a fall in TGV and improved patient survival (P = 0.015). Neither a reduction in the maximum standardized uptake value (P = 0.097) nor CT (P = 0.131) demonstrated a statistically significant association with patient survival.
Semiquantitative (18)F-FDG PET using the volume-based parameter of TGV is feasible in mesothelioma and may predict response to chemotherapy and patient survival after 1 cycle of treatment. Therefore, metabolic imaging has the potential to improve the care of patients receiving chemotherapy for mesothelioma by the early identification of responding patients. This technology may also be useful in the assessment of new systemic treatments for mesothelioma.
Journal of Nuclear Medicine 10/2007; 48(9):1449-58. · 6.38 Impact Factor
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ABSTRACT: Recent randomised trials have demonstrated a statistically significant effect of trastuzumab on disease-free survival when used as adjuvant therapy for human epidermal growth factor receptor 2 protein (HER2)-positive resectable early stage breast cancer, with a treatment course lasting either 9 or 52 weeks. However, the cost effectiveness of adjuvant trastuzumab with respect to mortality remains uncertain, especially in an Australian setting.
To estimate the cost effectiveness of trastuzumab in Australia, in a cohort of 50-year-old patients with HER2-positive breast cancer over a lifetime, using (i) disease-free survival and cardiotoxicity data from recent randomised trials; (ii) information on long-term survival of patients with treated primary breast cancer; and (iii) costs of treating local and distant relapses and disease from causes other than breast cancer.
A Markov model consisting of four health states (remission, loco-regional recurrence, metastatic disease and death) was developed. Transition probabilities corresponded to patterns of relapse and metastases seen in recent trials. The model was run until age 100 years to allow calculation of average survival. Outcome measures were life-years and QALYs (calculated using utility weights reported in the literature). The model was calibrated to reflect literature evidence that the risk of breast cancer recurrence following primary treatment diminishes progressively to zero after about 20 years. It was assumed that the morbidity benefit of trastuzumab observed in trials would be present for 5 years but would then diminish progressively to zero after 8 years. Costs (year 2005 values) and benefits were discounted at 3% per annum.
For every 1000 patients treated with a 52-week course of trastuzumab, there were 136 fewer breast cancer deaths (relative risk reduction 28%). The incremental cost-effectiveness ratios (ICERs) were Australian dollars ($ A)13 730 per year of life saved (YOLS) and $ A22 793 per QALY. The net incremental cost was $ A56.3 million ($ A414 012/cancer death avoided). Cost effectiveness declined (ICER = $ A27 734/QALY) in older patients (age 65 years at treatment initiation). The ICER was driven mainly by the drug acquisition costs, the assumption of the duration of benefit and the discount rate. Cost offsets from reduced costs of treating recurrent or metastatic breast cancer during follow-up were present but these factors were of less importance according to sensitivity analyses. The 9-week treatment schedule approached economic dominance (ICER = $ A1700/QALY) because of decreased costs, improved relative risk for prevention of metastases and more cancer deaths avoided (196).
The results suggest that trastuzumab as adjuvant therapy for early breast cancer may be cost effective when given over either 52 or 9 weeks at current acquisition costs in Australia. However, the overall budget impact of the 52-week course is significant, and the 9-week course appears economically attractive.
PharmacoEconomics 02/2007; 25(5):429-42. · 2.66 Impact Factor
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ABSTRACT: Tumor spread to distant organs is the most serious consequence of melanoma, as only 10-20% of stage IV patients respond to current chemotherapies. Tumor sensitivity to alkylating agents is affected by the activity of cellular DNA repair proteins, such as O(6)-methylguanine DNA methyltransferase (MGMT) and the DNA mismatch repair proteins. Chemosensitivity may be enhanced by reduced MGMT activity, but the frequency of MGMT promoter silencing through hypermethylation is unknown in distant melanoma metastases. The frequency and significance of microsatellite instability (MSI) in metastatic melanoma is also unclear, and it has been suggested that MSI frequency increases during the metastatic process. We undertook an analysis of 84 melanoma metastases from 47 patients. MGMT methylation was detected using methylation-specific PCR in 26 of the 84 metastases (31%), but there was discordance between individual metastases from the same patient. Therefore, as a result of this variation, MGMT methylation may have only limited value as a predictor of chemosensitivity. High MSI involving mononucleotide repeat markers was not found. Low MSI was detected in five of 50 metastases (10%) and only one of the five metastases also had MGMT methylation. These results demonstrate that in contrast to some previous reports, these tumors have a low frequency of MSI.
Journal of Investigative Dermatology 02/2006; 126(1):167-71. · 6.31 Impact Factor
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ABSTRACT: To determine the activity and tolerability of SAM496A, an inhibitor of S-adenosylmethionine decarboxylase (SAMDC), in patients with metastatic melanoma who had not received prior chemotherapy. Selected patients were offered participation in two sub-studies examining early changes in tumor metabolism with FDG-PET and changes in tumor polyamine content.
Fifteen patients with measurable metastatic melanoma, normal cardiac function, and no known CNS metastases were eligible and received SAM486A by 1-hour IV infusion daily for 5 days every 3 weeks. Response was assessed by SWOG criteria.
No patient had a confirmed partial response. Fatigue/lethargy, myalgia and neutropenia were the main toxicities but no febrile neutropenia or grade 4 non-hematological toxicity occurred. Five patients had PET scans pre-treatment and on days 8-12 of cycle 1. No patient had reduction of tumor metabolism. Serial biopsy in one patient showed alterations in polyamines consistent with SAMDC inhibition.
Using the present dose and schedule of administration, SAM486A does not have significant therapeutic potential in patients with metastatic melanoma.
Investigational New Drugs 07/2005; 23(3):253-6. · 3.36 Impact Factor
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Anthony T C Chan,
Mow-Ming Hsu,
Boon C Goh,
Edwin P Hui,
Tsang-Wu Liu, Michael J Millward,
Ruey-Long Hong,
Jacqueline Whang-Peng,
Brigette B Y Ma,
Ka F To,
Matthias Mueser,
Nadia Amellal,
Xiao Lin,
Alex Y Chang
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ABSTRACT: To evaluate efficacy and toxicity of cetuximab plus carboplatin in recurrent or metastatic nasopharyngeal carcinoma (NPC) resistant to platinum treatment.
A multicenter, open-label, single-arm, phase II study in patients with epidermal growth factor receptor-expressing NPC who progressed on or within 12 months after termination of platinum-based chemotherapy for recurrent or metastatic disease. Cetuximab was administered at an initial dose of 400 mg/m2 followed by weekly doses of 250 mg/m2. Carboplatin area under the curve 5 was administered every 3 weeks up to a maximum of eight cycles.
Sixty patients were enrolled (46 males, 14 females; median age, 44.5 years; range, 23 to 64 years), and all patients were included in the intent-to-treat and safety analyses. Of the 59 patients assessable for efficacy, there were seven partial responses (11.7%), 29 patients (48.3%) with stable disease, and 23 patients (38.3%) with progressive disease, giving an overall response rate of 11.7% (95% CI, 4.8% to 22.6%). The median time to progression was 81 days in all patients and was longest in the group of patients with a confirmed response (173 days). The median overall survival time was 233 days in all patients. Six patients (10%) experienced serious treatment-related adverse events. Grade 3 or 4 toxicities occurred in 31 patients (51.7%); of these patients, only 19 (31.7%) were considered to have toxicity related to cetuximab.
Cetuximab in combination with carboplatin demonstrates clinical activity and an acceptable safety profile in heavily pretreated patients with recurrent or metastatic NPC who had previously experienced treatment failure with platinum-based therapy.
Journal of Clinical Oncology 06/2005; 23(15):3568-76. · 18.37 Impact Factor
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ABSTRACT: Malignant pleural mesothelioma is an aggressive malignancy which is almost always fatal; median survival is usually < 1 year. Most patients present with symptoms including pain, dyspnoea, pleural effusions and chest wall masses. Until recently, there has been no effective treatment which can improve symptoms and prolong survival. This article reviews recent developments in the treatment of mesothelioma, particularly advances in drug therapy and the use of the current most active drug combination: pemetrexed and cisplatin. Pemetrexed is a novel antifolate drug with multiple enzyme targets. The combination of pemetrexed and cisplatin demonstrated a survival advantage over cisplatin alone in patients with pleural mesothelioma, and can give symptomatic benefits. This combination has become the standard of care in mesothelioma treatment.
Expert Opinion on Pharmacotherapy 12/2004; 5(12):2441-9. · 3.20 Impact Factor
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ABSTRACT: To determine the maximally tolerated dose (MTD) of gemcitabine administered at a fixed dose-rate of 10 mg/m(2) per min in combination with fixed dose carboplatin, to evaluate the toxicity of this regimen and to determine the pharmacokinetics of plasma gemcitabine.
Patients with advanced stage non-small-cell lung cancer (NSCLC) received carboplatin (AUC 5) on day 1 followed by gemcitabine at a fixed dose rate of 10 mg/m(2) per min in escalating durations of infusion on days 1 and 8 every 21 days. Pharmacokinetic sampling was obtained on day 1, cycle 1 of treatment.
A total of 15 patients received carboplatin and gemcitabine in cohorts of three to six patients at three dose levels. The doses of gemcitabine studied were 600, 750, and 900 mg/m(2). The MTD was reached at 900 mg/m(2). Dose-limiting toxicities were thrombocytopenia and liver failure, and with repeated dosing neutropenia was commonly observed. The recommended phase II dose of gemcitabine was 750 mg/m(2). Partial responses were observed at 600 and 750 mg/m(2) of gemcitabine. Plasma gemcitabine did not reach steady state except in one patient with the durations of infusion studied. Plasma concentrations, however, were above 10 micro mol/l between 20 and 90 min in all patients.
Gemcitabine administered as a 75-min infusion at a fixed dose rate of 10 mg/m(2)/min on days 1 and 8 in combination with carboplatin on day 1 every 21 days is tolerable and active in NSCLC. Pharmacokinetic studies demonstrated that the target plasma gemcitabine concentration above 10 micro mol/l was achieved. Further studies are warranted to compare this regimen against standard regimens of carboplatin and gemcitabine.
Cancer Chemotherapy and Pharmacology 09/2003; 52(2):153-8. · 2.83 Impact Factor
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International Journal of Cancer 11/2002; 101(4):398-9. · 5.44 Impact Factor
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Karl D Lewis,
William A Robinson, Michael J Millward,
Alex Powell,
Timothy J Price,
Damien B Thomson,
Euan T Walpole,
Andrew M Haydon,
Brian R. Creese,
Kaye L. Roberts,
John R Zalcberg,
Rene Gonzalex
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ABSTRACT: Treatment options for advanced melanoma are limited. PI-88, a potent inhibitor of heparanase, demonstrates anitangiogenic properties and has shown activity against melanoma in phase I studies. This was an open-label, multicenter, phase II study of PI-88 in patients with advanced melanoma. Patients received a fixed-dose of 250 mg/day given subcutaneously for four consecutive days followed by three drug-free days per week in a 28-day cycle. A total of 44 patients were enrolled in the intent to treat population, with 59.1% having received previous therapy. The median time to progression and overall survival was 1.7 months and 9 months, respectively. Forty-one patients are included in the efficacy analysis. One (2.4%) patient achieved a partial response, six (14.6%) patients had stable disease as best response, and 30 (73.2%) had progressive disease. At the end of six cycles of treatment, three of the 41 evaluable patients had non-progressive disease. Treatment was generally well tolerated. Injection site bruising occurred in 45% of patients. Serious bleeding did occur in two patients and three patients developed a positive anti-platelet antibody test during the study. One of these four patients experienced an associated thrombosis. In patients with advanced melanoma, PI-88 demonstrates an overall survival and time to progression similar to standard chemotherapy. Although the current study did not meet the primary end-point of progression free survival of >/=20%, there is some evidence of activity and further investigation is warranted.
