David Goldstein

Publications

• 17.79

  Impact points

  Cancer-Related Fatigue in Women With Breast Cancer: Outcomes of a 5-Year Prospective Cohort Study.

  David Goldstein, Barbara K Bennett, Kate Webber, Fran Boyle, Paul L de Souza, Nicholas R C Wilcken, Elizabeth M Scott, Ruth Toppler, Penelope Murie, Linda O'Malley, Junie McCourt, Michael Friedlander, Ian B Hickie, Andrew R Lloyd

  Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 04/2012;

  PURPOSEProlonged and disabling fatigue is prevalent after cancer treatment, but the early natural history of cancer-related fatigue (CRF) has not been systematically examined to document consistent presence of symptoms. Hence, relationships to cancer, surgery, and adjuvant therapy are unclear. PATIE... [more] PURPOSEProlonged and disabling fatigue is prevalent after cancer treatment, but the early natural history of cancer-related fatigue (CRF) has not been systematically examined to document consistent presence of symptoms. Hence, relationships to cancer, surgery, and adjuvant therapy are unclear. PATIENTS AND METHODSA prospective cohort study of women receiving adjuvant treatment for early-stage breast cancer was conducted. Women (n = 218) were enrolled after surgery and observed at end treatment and at 1, 3, 6, 9, and 12 months as well as 5 years. Structured interviews and self-report questionnaires were used to record physical and psychologic health as well as disability and health care utilization. Patients with CRF persisting for 6 months were assessed to exclude alternative medical and psychiatric causes of fatigue. Predictors of persistent fatigue, mood disturbance, and health care utilization were sought by logistic regression.ResultsThe case rate for CRF was 24% (n = 51) postsurgery and 31% (n = 69) at end of treatment; it became persistent in 11% (n = 24) at 6 months and 6% (n = 12) at 12 months. At each time point, approximately one third of the patients had comorbid mood disturbance. Persistent CRF was predicted by tumor size but not demographic, psychologic, surgical, or hematologic parameters. CRF was associated with significant disability and health care utilization. CONCLUSIONCRF is common but generally runs a self-limiting course. Much of the previously reported high rates of persistent CRF may be attributable to factors unrelated to the cancer or its treatment.
• 2.09

  Impact points

  Impact of oxaliplatin-induced neuropathy: a patient perspective.

  Barbara K Bennett, Susanna B Park, Cindy S-Y Lin, Michael L Friedlander, Matthew C Kiernan, David Goldstein

  Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 03/2012;

  INTRODUCTION: Dose-limiting neurotoxicity is a major side effect of oxaliplatin treatment, producing initial acute neurotoxicity and chronic neuropathy with increasing exposure. The improvement in survival for patients with early-stage colorectal cancer treated with oxaliplatin has highlighted the n... [more] INTRODUCTION: Dose-limiting neurotoxicity is a major side effect of oxaliplatin treatment, producing initial acute neurotoxicity and chronic neuropathy with increasing exposure. The improvement in survival for patients with early-stage colorectal cancer treated with oxaliplatin has highlighted the need for valid and reliable assessment of peripheral neuropathy. OBJECTIVES: The objective of this paper was to explore neuropathic symptoms in oxaliplatin-treated patients as assessed using different methods. METHODS: Consecutive symptomatic patients reporting peripheral neuropathy after oxaliplatin chemotherapy for colorectal cancer were interviewed using a semi-structured clinical interview. Neurotoxicity was also assessed using the National Cancer Institute Common Toxicity Criteria scale (clinician-rated), patient 'self-report' questionnaires (PNQ), nerve conduction and clinical assessment. RESULTS: Twenty patients were assessed, 12.6 ± 2.8 months after treatment cessation (mean cumulative oxaliplatin dose, 789 mg/m(2)). In 40% of patients, neurotoxicity necessitated early cessation of treatment. Only 10% of patients were designated by clinicians with severe neurotoxicity, whilst, in contrast, patient interviews and self-report questionnaires described significant physical limitations due to neuropathic symptoms in 60% of patients. The majority (85%) of patients had objective evidence of sensory neuropathy with nerve conduction studies. Reports from clinical interviews were strongly correlated with patient self-assessment (Pearson coefficient = 0.790, p < 0.0005). CONCLUSION: Given the discrepancies in symptom prevalence highlighted by these findings, the monitoring of oxaliplatin-induced neurotoxicity would benefit from more informative clinical assessment, with inclusion of patient-reported outcome measures. Such an approach would be beneficial in a clinical trial setting to monitor the efficacy of interventions and in prospective studies of survivorship to determine the true burden of peripheral neuropathy in oxaliplatin-treated patients.
• 14.47

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  Psychological morbidity and quality of life of ethnic minority patients with cancer: a systematic review and meta-analysis.

  Tim Luckett, David Goldstein, Phyllis N Butow, Val Gebski, Lynley J Aldridge, Joshua McGrane, Weng Ng, Madeleine T King

  The lancet oncology. 12/2011; 12(13):1240-8.

  Ethnic minority is associated with higher cancer incidence and poorer survival than is being in the majority group. We did a systematic review and meta-analysis to assess whether psychological morbidity and health-related quality of life (HRQoL) were affected by minority status. We searched Medline,... [more] Ethnic minority is associated with higher cancer incidence and poorer survival than is being in the majority group. We did a systematic review and meta-analysis to assess whether psychological morbidity and health-related quality of life (HRQoL) were affected by minority status. We searched Medline, AMED, PsycINFO, Embase, CENTRAL, CINAHL, PubMed, Sociological Abstracts, and Web of Science for English-language articles published between Jan 1, 1995, and October, 2009. Articles were eligible if they reported original data on anxiety, depression, distress (for psychological morbidity), or HRQoL in minority and majority cancer patients or survivors. Minority status was defined as being an immigrant or having an ethnic, linguistic, or religious background different to the majority of the population in the country where the research was done. We excluded African Americans and indigenous groups. Eligible articles were rated for quality of reporting, external validity, internal validity, sample size, and power. Each quality criterion was rated independently by two reviewers until inter-rater reliability was achieved. In a meta-analysis we compared mean scores adjusted for socioeconomic status and other sociodemographic and clinical variables, where available. Effect sizes greater than 0·5 and 95% CI that included 0·5 or -0·5 were deemed clinically important, with negative values indicating worse outcomes in minority patients. We assessed publication bias by estimating the number of potential unpublished studies and the number of non-signficant studies with p=0·05 required to produce a non-significant overall result. We identified 21 eligible articles that included 18 datasets collected in the USA and one in each of Canada, Romania, and the UK. Ethnic minority groups were Hispanic, Asian or Pacific Islander, or Hungarian (one dataset). Overall, we found minority versus majority groups to have significantly worse distress (mean difference -0·37, 95% CI -0·46 to -0·28; p<0·0001), depression (-0·23, -0·36 to -0·11; p=0·0003), and overall HRQoL (-0·33, -0·58 to -0·07; p=0·013). Further analyses found disparities to be specific to Hispanic patients in the USA, in whom poorer outcomes were consistent with potentially clinically important differences for distress (effect size -0·37, 95% CI -0·54 to -0·20; p<0·0001), social HRQoL (-0·45, -0·87 to -0·03; p=0·035), and overall HRQoL (-0·49, -0·78 to -0.20; p=0·0008). Results were significantly heterogeneous for overall HRQoL and all domains. Tests for interaction, for adjusted versus unadjusted and comparisons of high-quality, medium-quality, and low-quality articles, were generally non-significant, which suggests no bias. We found no evidence of any substantive publication bias. Hispanic cancer patients in the USA, but not other ethnic minority groups, report significantly worse distress, depression, social HRQoL, and overall HRQoL than do majority patients, of which all but depression might be clinically important. Heterogeneous results might, however, have limited the interpretation. Data for other minority groups and for anxiety are scarce. More studies are needed from outside the USA. Future reports should more clearly describe their minority group samples and analyses should control for clinical and sociodemographic variables known to predict outcomes. Understanding of why outcomes are poor in US Hispanic patients is needed to inform the targeting of interventions. Prince of Wales Hospital, Sydney, Australia.
• 2.09

  Impact points

  Psychosocial well-being and supportive care needs of cancer patients living in urban and rural/regional areas: a systematic review.

  Phyllis N Butow, Fiona Phillips, Janine Schweder, Kate White, Craig Underhill, David Goldstein

  Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 09/2011; 20(1):1-22.

  The aim of this study was to describe what is known about levels of morbidity and the experience and needs of people with cancer, and their informal caregivers, living in rural areas. A search of online databases for English language papers describing or assessing the prevalence of psychosocial morb... [more] The aim of this study was to describe what is known about levels of morbidity and the experience and needs of people with cancer, and their informal caregivers, living in rural areas. A search of online databases for English language papers describing or assessing the prevalence of psychosocial morbidity or needs in a population of rural or regional cancer patients was employed. The following were excluded: intervention studies, discussion of service delivery, effectiveness of support groups or support via videoconferencing, concentrated on medical outcomes or survival rates, reported differences in the uptake of cancer screening or concentrated on health attitudes or treatment decision making. There were 37 studies in the review, including 25 quantitative studies (all surveys), 11 of which included a control group of urban patients and 12 qualitative studies. Until recently, most studies had methodological shortcomings. Only two prospective studies were identified, most studies focused on breast cancer and few addressed psychological morbidity. The majority of controlled studies reported worse outcomes for rural patients, who appear to have higher needs in the domains of physical/daily living. This may reflect more limited access to resources, a more self-sufficient lifestyle and personal characteristics, for example, being more stoical and less likely to ask for help. The need to travel for treatment caused many practical, emotional and financial problems for patients and burdened them with additional worry concerning family and work commitments. Some patients reported benefits in sharing experiences with others also forced to stay away from home, but most agreed that staying at home was preferable. This review highlights that whilst we are beginning to get some insight into the needs of people with cancer in rural areas, much is still unknown. Population-based, prospective studies including people with heterogeneous cancers from rural and urban settings are needed.
• 6.70

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  If I am in the mood, I enjoy it: an exploration of cancer-related fatigue and sexual functioning in women with breast cancer.

  Kate Webber, Kelly Mok, Barbara Bennett, Andrew R Lloyd, Michael Friedlander, Ilona Juraskova, David Goldstein

  The oncologist. 08/2011; 16(9):1333-44.

  We recently reported that cancer-related fatigue (CRF) after adjuvant breast cancer therapy was prevalent and disabling, but largely self-limiting within 12 months. The current paper describes sexual functioning (SF) and its relationship to CRF, mood disorder, and quality of life (QOL) over the firs... [more] We recently reported that cancer-related fatigue (CRF) after adjuvant breast cancer therapy was prevalent and disabling, but largely self-limiting within 12 months. The current paper describes sexual functioning (SF) and its relationship to CRF, mood disorder, and quality of life (QOL) over the first year after completion of adjuvant therapy. Women were recruited after surgery, but prior to commencing adjuvant treatment, for early-stage breast cancer. Self-reported validated questionnaires assessed SF, CRF, mood, menopausal symptoms, disability, and QOL at baseline, completion of therapy, and at 6 months and 12 months after treatment. Of the 218 participants, 92 (42%) completed the SF measure (mean age, 50 years). They were significantly younger, more likely to be partnered, and less likely to be postmenopausal than nonresponders. At baseline, 40% reported problems with sexual interest and 60% reported problems with physical sexual function. SF scores declined across all domains at the end of treatment, then improved but remained below baseline at 12 months, with a significant temporal effect in the physical SF subscale and a trend for overall satisfaction. There were significant correlations between the SF and QOL domains (physical and emotional health, social functioning, and general health) as well as overall QOL. The presence of mood disorder, but not fatigue, demographic, or treatment variables, independently predicted worse overall sexual satisfaction. Sexual dysfunction is common after breast cancer therapy and impacts QOL. Interventions should include identification and treatment of concomitant mood disorder.
• 17.79

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  Neuroprotection for oxaliplatin-induced neurotoxicity: what happened to objective assessment?

  Susanna B Park, David Goldstein, Cindy S-Y Lin, Arun V Krishnan, Michael L Friedlander, Matthew C Kiernan

  Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 06/2011; 29(18):e553-4; author reply e555-6.
• 17.79

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  Interpretation in consultations with immigrant patients with cancer: how accurate is it?

  Phyllis N Butow, David Goldstein, Melaine L Bell, Ming Sze, Lynley J Aldridge, Sarah Abdo, Michelle Tanious, Skye Dong, Rick Iedema, Janette Vardy, Ray Ashgari, Rina Hui, Maurice Eisenbruch

  Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 06/2011; 29(20):2801-7.

  Immigrants with cancer often have professional and/or family interpreters to overcome challenges communicating with their health team. This study explored the rate and consequences of nonequivalent interpretation in medical oncology consultations. Consecutive immigrant patients with newly diagnosed ... [more] Immigrants with cancer often have professional and/or family interpreters to overcome challenges communicating with their health team. This study explored the rate and consequences of nonequivalent interpretation in medical oncology consultations. Consecutive immigrant patients with newly diagnosed with incurable cancer, who spoke Arabic, Cantonese, Mandarin, or Greek, were recruited from the practices of 10 medical oncologists in nine hospitals. Their first two consultations were audio taped, transcribed, translated into English and coded. Thirty-two of 78 participants had an interpreter at 49 consultations; 43% of interpreters were family, 35% professional, 18% both a professional and family, and 4% a health professional. Sixty-five percent of professional interpretations were equivalent to the original speech versus 50% for family interpreters (P= .02). Seventy percent of nonequivalent interpretations were inconsequential or positive; however, 10% could result in misunderstanding, in 5% the tone was more authoritarian than originally intended, and in 3% more certainty was conveyed. There were no significant differences in interpreter type for equivalency of interpretations. Nonequivalent interpretation is common, and not always innocuous. Our study suggests that there may remain a role for family or telephone versus face-to-face professional interpreters. Practice implications: careful communication between oncologists and interpreters is required to ensure optimal communication with the patient.
• 4.12

  Impact points

  Single-agent irinotecan or FOLFIRI as second-line chemotherapy for advanced colorectal cancer; results of a randomised phase II study (DaVINCI) and meta-analysis [corrected].

  Stephen J Clarke, Sonia Yip, Chris Brown, Guy A van Hazel, David T Ransom, David Goldstein, G Mark Jeffrey, Niall C Tebbutt, Martin Buck, Raymond M Lowenthal, Amy Boland, Val Gebski, John Zalcberg, R John Simes

  European journal of cancer (Oxford, England : 1990). 06/2011; 47(12):1826-36.

  Second-line treatment with irinotecan for advanced or metastatic colorectal cancer prolongs survival. It is uncertain whether irinotecan is better administered with 5-fluorouracil or alone in patients previously treated with a fluoropyrimidine. We compared toxicity (particularly diarrhoea), quality ... [more] Second-line treatment with irinotecan for advanced or metastatic colorectal cancer prolongs survival. It is uncertain whether irinotecan is better administered with 5-fluorouracil or alone in patients previously treated with a fluoropyrimidine. We compared toxicity (particularly diarrhoea), quality of life, and efficacy of combination chemotherapy and irinotecan in these patients. In DaVINCI, a randomised phase II trial, patients with advanced colorectal cancer were randomly allocated to: Combination therapy (FOLFIRI), irinotecan (180 mg/m(2) IV over 90 min, day 1), 5-fluorouracil (400mg/m(2) IV bolus and 2400 mg/m(2) by 46-hour infusion from day 1) and folinic acid (20mg/m(2) IV bolus, day 1), 2-weekly; or Single-agent, irinotecan (350 mg/m(2) IV over 90 min), 3-weekly. Toxicity was evaluated every treatment cycle; QOL and response 6-weekly. Analysis was by intention to treat. The trial, amended from a larger factorial design, was terminated early due to slow recruitment. Results were also combined with other second-line irinotecan trials. We randomised 44 patients to combination and 45 to single agent. Eight patients in the irinotecan arm and 4 in the combination arm had grade 3/4 diarrhoea (P=0.24). Treatment groups did not differ significantly in overall QOL changes, response rate or progression free or overall-survival. In a systematic review of 29 trials of second-line irinotecan-based treatment, single-agent irinotecan was associated with more diarrhoea and alopecia than the combination but efficacy was similar. Combination treatment compared with single-agent irinotecan reduces alopecia and diarrhoea without compromising efficacy on clinical outcomes. Both regimens remain as reasonable treatment options. Research grant (Pfizer).
• 1.79

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  Management of metastatic renal cell carcinoma in the era of targeted therapies.

  K Webber, A Cooper, H Kleiven, D Yip, D Goldstein

  Internal medicine journal. 06/2011; 41(8):594-605.

  Metastatic renal cell cancer is associated with poor prognosis and survival and is resistant to conventional chemotherapy. Therapeutic targeting of molecular pathways for tumour angiogenesis and other specific activation mechanisms offers improved tumour response and prolonged survival. To conduct a... [more] Metastatic renal cell cancer is associated with poor prognosis and survival and is resistant to conventional chemotherapy. Therapeutic targeting of molecular pathways for tumour angiogenesis and other specific activation mechanisms offers improved tumour response and prolonged survival. To conduct a retrospective audit of metastatic renal cell carcinoma patients treated with targeted therapies. Data were extracted from clinical records of patients undergoing targeted treatment between 2005 and 2009 at two hospital sites. Data collected included pathology, systemic therapy class, toxicity and survival. Univariate and multivariate survival analyses were performed. Sixty-one patients were treated with 102 lines of therapy with a median overall survival (OS) of 23 months, median time to failure of first-line treatment (TTF1) of 10 months and median time to failure of second-line treatment (TTF2) of 5.2 months. Time from first diagnosis to treatment >12 months was significantly associated with improved OS, longer TTF1, TTF2 and response to first-line anti-vascular endothelial growth factor receptor tyrosine kinase inhibitors (anti-VEGF TKI) therapy. Variables associated with tumour biology, natural history and the systemic inflammatory response were associated with improved OS and TTF1. Development of hypertension was predictive of anti-VEGF TKI outcome. Toxicities were as expected for each drug class.   Survival and toxicity outcomes from two Australian sites are comparable to published data. The adverse event profile differs to conventional chemotherapy. Clinicians caring for patients with metastatic renal cancer will need to become familiar with these toxicities and their management as these agents enter widespread use.
• 17.79

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  Supporting treatment decision making in advanced cancer: a randomized trial of a decision aid for patients with advanced colorectal cancer considering chemotherapy.

  Natasha B Leighl, Heather L Shepherd, Phyllis N Butow, Stephen J Clarke, Margaret McJannett, Philip J Beale, Nicholas R C Wilcken, Malcolm J Moore, Eric X Chen, David Goldstein, Lisa Horvath, Jennifer J Knox, Monika Krzyzanowska, Amit M Oza, Ronald Feld, David Hedley, Wei Xu, Martin H N Tattersall

  Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 05/2011; 29(15):2077-84.

  Decision making in advanced cancer is increasingly complex. We developed a decision aid (DA) for patients with advanced colorectal cancer who are considering first-line chemotherapy and reviewing treatment options, prognostic information, and toxicities. We examined its impact on patient understandi... [more] Decision making in advanced cancer is increasingly complex. We developed a decision aid (DA) for patients with advanced colorectal cancer who are considering first-line chemotherapy and reviewing treatment options, prognostic information, and toxicities. We examined its impact on patient understanding, treatment decisions, decisional conflict, decision making, consultation satisfaction, anxiety, and quality of life by using a randomized trial design. In all, 207 patients with colorectal cancer who were considering first-line chemotherapy for metastatic disease were randomly assigned to receive a standard medical oncology consultation or a consultation in which the DA (take-home booklet with audio recording, reviewed by an oncologist) was used. Participants completed questionnaires postconsultation, postdecision, and 1 month later. In this study, 100 patients were randomly assigned to the control arm, and 107 received the DA. Median age of the sample was 62 years, 58% were male, 89% had a performance status of 0 or 1, and 36% had received prior adjuvant chemotherapy. Patients receiving the DA demonstrated a greater increase in understanding of prognosis, options, and benefits, with higher overall understanding (P < .001). Decisional conflict, treatment decisions, and achievement of involvement preferences were similar between the groups. Anxiety was similar across groups and decreased over time. Most patients were confident in a decision during the first consultation; 74% chose chemotherapy, 7% supportive care alone, and 10% observation. This randomized trial of a decision aid in advanced cancer showed that its use in advanced colorectal cancer improved patient understanding of prognosis, treatment options, risks, and benefits without increasing anxiety. DAs can improve informed consent and can be tested through randomized trials even in the advanced cancer setting.
• 1.98

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  Grappling with cultural differences; communication between oncologists and immigrant cancer patients with and without interpreters.

  Phyllis Butow, Melanie Bell, David Goldstein, Ming Sze, Lynley Aldridge, Sarah Abdo, Michelle Mikhail, Skye Dong, Rick Iedema, Ray Ashgari, Rina Hui, Maurice Eisenbruch

  Patient education and counseling. 03/2011; 84(3):398-405.

  Immigrants report challenges communicating with their health team. This study compared oncology consultations of immigrants with and without interpreters vs Anglo-Australian patients. Patients with newly diagnosed incurable cancer who had immigrated from Arabic, Chinese or Greek speaking countries o... [more] Immigrants report challenges communicating with their health team. This study compared oncology consultations of immigrants with and without interpreters vs Anglo-Australian patients. Patients with newly diagnosed incurable cancer who had immigrated from Arabic, Chinese or Greek speaking countries or were Anglo-Australian, and family members, were recruited from 10 medical oncologists in 9 hospitals. Two consultations from each patient were audio-taped, transcribed, translated into English and coded. Seventy-eight patients (47 immigrant and 31 Anglo-Australian) and 115 family members (77 immigrant and 38 Anglo Australian) participated in 141 audio-taped consultations. Doctors spoke less to immigrants with interpreters than to Anglo-Australians (1443 vs. 2246 words, p=0.0001), spent proportionally less time on cancer related issues (p=0.005) and summarising and informing (p≤0.003) and more time on other medical issues (p=0.0008) and directly advising (p=0.0008). Immigrants with interpreters gave more high intensity cues (10.4 vs 7.4). Twenty percent of cues were not interpreted. Doctors tended to delay responses to or ignore more immigrant than Anglo-Australian cues (13% vs 5%, p=0.06). Immigrant cancer patients with interpreters experience different interactions with their doctors than Anglo-Australians, which may compromise their well-being and decisions. Guidelines and proven training programmes are needed to improve communication with immigrant patients, particularly those with interpreters.
• 2.40

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  Risk and response adapted therapy for early stage Hodgkin lymphoma: a prospective multicenter study of the Australasian Leukaemia and Lymphoma Group/Trans-Tasman Radiation Oncology Group.

  Andrew Wirth, Andrew Grigg, Max Wolf, David Goldstein, Carol Johnson, Sidney Davis, Gaelle Dutu, Poppy Kypreos, Carole Smith, Andrew Kneebone, Mark Herzberg, David Joseph, John Catalano, Daniel Roos, Janey Stone, John Reynolds

  Leukemia & lymphoma. 02/2011; 52(5):786-95.

  In this prospective, multicenter, non-randomized study for patients with stage I-II Hodgkin lymphoma, group 1 (without risk-factors [RF]) had three cycles of ABVD chemotherapy (adriamycin, bleomycin, vinblastine, and dacarbazine) and group 2 (any of bulk, extranodal site, >3 regions, raised eryth... [more] In this prospective, multicenter, non-randomized study for patients with stage I-II Hodgkin lymphoma, group 1 (without risk-factors [RF]) had three cycles of ABVD chemotherapy (adriamycin, bleomycin, vinblastine, and dacarbazine) and group 2 (any of bulk, extranodal site, >3 regions, raised erythrocyte sedimentation rate [ESR]) and group 3 (B-symptoms) received four cycles. Involved field radiotherapy (IFRT) 30 Gy was given after adequate chemotherapy response. Five-year overall survival and freedom from progression (FFP) were 96% (95% confidence interval [CI] 91-98%) and 90% (84-94%), respectively. Five-year FFP was 97% (90-99%), 89% (75-95%), and 73% (52-86%) for groups 1, 2, and 3, respectively. In patients with RF, chemotherapy responses of complete response unconfirmed (CRu), partial response (PR), and stable disease (SD) were associated with FFP of 90%, 86%, and 62% (p=0.17), and CR/no CR on functional imaging with FFP of 90%/67%, respectively (p=0.05). The 97% FFP in group 1 compares favorably with previously reported results from cooperative trial groups. Intensification of therapy warrants study in patients with RF and a poor chemotherapy response.
• 4.41

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  Dose effects of oxaliplatin on persistent and transient Na+ conductances and the development of neurotoxicity.

  Susanna B Park, Cindy S-Y Lin, Arun V Krishnan, David Goldstein, Michael L Friedlander, Matthew C Kiernan

  PloS one. 01/2011; 6(4):e18469.

  Oxaliplatin, a platinum-based chemotherapy utilised in the treatment of colorectal cancer, produces two forms of neurotoxicity--acute sensorimotor neuropathic symptoms and a dose-limiting chronic sensory neuropathy. Given that a Na(+) channelopathy has been proposed as the mechanism underlying acute... [more] Oxaliplatin, a platinum-based chemotherapy utilised in the treatment of colorectal cancer, produces two forms of neurotoxicity--acute sensorimotor neuropathic symptoms and a dose-limiting chronic sensory neuropathy. Given that a Na(+) channelopathy has been proposed as the mechanism underlying acute oxaliplatin-induced neuropathy, the present study aimed to determine specific mechanisms of Na(+) channel dysfunction. Specifically the function of transient and persistent Na(+) currents were followed during treatment and were investigated in relation to oxaliplatin dose level. Eighteen patients were assessed before and after a single oxaliplatin infusion with motor and sensory axonal excitability studies performed on the median nerve at the wrist. While refractoriness (associated with Na(+) channel inactivation) was significantly altered post-oxaliplatin infusion in both motor (Pre: 31.7±6.4%; Post: 68.8±14.5%; P≤.001) and sensory axons (Pre: 31.4±5.4%; Post: 21.4±5.5%; P<.05), strength-duration time constant (marker of persistent Na(+) conductances) was not significantly altered post-infusion (Motor Pre: 0.395±0.01 ms; Post: 0.394±0.02 ms; NS; Sensory Pre:0.544±0.03 ms; Post: 0.535±0.05 ms; NS). However, changes in strength-duration time constant were significantly correlated with changes in refractoriness in motor and sensory axons (Motor correlation coefficient = -.65; P<.05; Sensory correlation coefficient = .67; P<.05). It is concluded that the predominant effect of acute oxaliplatin exposure in human motor and sensory axons is mediated through changes in transient rather than persistent Na(+) conductances. These findings are likely to have implications for the design and trial of neuroprotective strategies.
• 6.70

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  Long-term neuropathy after oxaliplatin treatment: challenging the dictum of reversibility.

  Susanna B Park, Cindy S Y Lin, Arun V Krishnan, David Goldstein, Michael L Friedlander, Matthew C Kiernan

  The oncologist. 01/2011; 16(5):708-16.

  Oxaliplatin-induced neuropathy is a significant and dose-limiting toxicity that adversely affects quality of life. However, the long-term neurological sequelae have not been adequately described. The present study aimed to describe the natural history of oxaliplatin-induced neuropathy, using subject... [more] Oxaliplatin-induced neuropathy is a significant and dose-limiting toxicity that adversely affects quality of life. However, the long-term neurological sequelae have not been adequately described. The present study aimed to describe the natural history of oxaliplatin-induced neuropathy, using subjective and objective assessments. From a population of 108 oxaliplatin-treated patients referred for neurological assessment in 2002-2008, 52.2% of the surviving patient cohort (n = 24) was available for follow-up at a median of 25 months post-oxaliplatin. Patients underwent a protocol that incorporated clinical assessment scales, patient questionnaires, standard electrodiagnostic assessments, and novel nerve excitability studies to precisely assess nerve function. At follow-up, 79.2% of patients reported residual neuropathic symptoms, with distal loss of pin-prick sensibility in 58.3% of patients and loss of vibration sensibility in 83.3% of patients. Symptom severity scores were significantly correlated with cumulative dose. There was no recovery of sensory action potential amplitudes in upper and lower limbs, consistent with persistent axonal sensory neuropathy. Sensory excitability parameters had not returned to baseline levels, suggesting persisting abnormalities in nerve function. The extent of excitability abnormalities during treatment was significantly correlated with clinical outcomes at follow-up. These findings establish the persistence of subjective and objective deficits in oxaliplatin-treated patients post-oxaliplatin, suggesting that sensory neuropathy is a long-term outcome, thereby challenging the literature on the reversibility of oxaliplatin-induced neuropathy.
• 2.09

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  A bridge between cultures: interpreters' perspectives of consultations with migrant oncology patients.

  Phyllis N Butow, Elizabeth Lobb, Michael Jefford, David Goldstein, Maurice Eisenbruch, Afaf Girgis, Madeleine King, Ming Sze, Lynley Aldridge, Penelope Schofield

  Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 11/2010; 20(2):235-44.

  Migration is increasing worldwide. In previous research into people with cancer from culturally and linguistically diverse backgrounds, interpreter accuracy, professionalism and continuity have emerged as key concerns for patients. Little is known about interpreters' perceptions of their role an... [more] Migration is increasing worldwide. In previous research into people with cancer from culturally and linguistically diverse backgrounds, interpreter accuracy, professionalism and continuity have emerged as key concerns for patients. Little is known about interpreters' perceptions of their role and the challenges they face. This study aimed to obtain their perspective. Thirty interpreters (Greek n = 7, Chinese n = 11, and Arabic n = 12) participated in four focus groups which were audio-taped, transcribed and analysed for themes using N-Vivo software. Skills as an interpreter were broadly perceived as conveying information accurately, being confidential and impartial. Three broad dilemmas faced by interpreters emerged: accuracy versus understanding; translating only versus cultural advocacy and sensitivity; and professionalism versus providing support. Some saw themselves as merely an accurate conduit of information, while others saw their role in broader terms, encompassing patient advocacy, cultural brokerage and provision of emotional support. Perceived challenges in their role included lack of continuity, managing their own emotions especially after bad news consultations, and managing diverse patient and family expectations. Training and support needs included medical terminology, communication and counselling skills and debriefing. Interpreters suggested that oncologists check on interpreter/patient's language or dialect compatibility; use lay language and short sentences; and speak in the first person. Resolving potential conflicts between information provision and advocacy is an important area of cross-cultural communication research. Further training and support is required to enhance interpreters' competence in managing delicate situations from a professional, cultural and psychological perspective; and to assist doctors to collaborate with interpreters to ensure culturally competent communication. Ultimately, this will improve interpreters' well-being and patient care.
• 3.91

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  Utilizing natural activity to dissect the pathophysiology of acute oxaliplatin-induced neuropathy.

  Susanna B Park, Cindy S-Y Lin, Arun V Krishnan, David Goldstein, Michael L Friedlander, Matthew C Kiernan

  Experimental neurology. 10/2010; 227(1):120-7.

  Oxaliplatin is first-line chemotherapy for colorectal cancer, but produces dose-limiting neurotoxicity. Acute neurotoxicity following infusion produces symptoms including cold-triggered fasciculations and cramps, with subsequent chronic neuropathy developing at higher cumulative doses. Axonal excita... [more] Oxaliplatin is first-line chemotherapy for colorectal cancer, but produces dose-limiting neurotoxicity. Acute neurotoxicity following infusion produces symptoms including cold-triggered fasciculations and cramps, with subsequent chronic neuropathy developing at higher cumulative doses. Axonal excitability studies were undertaken in 15 oxaliplatin-treated patients before and immediately after oxaliplatin infusion to determine whether the mechanisms underlying acute neurotoxicity altered resting membrane potential or Na(+)/K(+) pump function. Excitability properties were assessed before and after maximal voluntary contraction (MVC) of the abductor pollicis brevis. Following oxaliplatin infusion, abnormalities developed in the recovery cycle with refractoriness markedly increased. Following activity, changes developed consistent with axonal hyperpolarization, with proportional changes pre- and post-oxaliplatin in normalized threshold. However, recovery cycle parameters following activity were significantly and disproportionally enhanced post-oxaliplatin, with partial normalization of the recovery cycle curve post-activity. Patients with the most abnormal change in the recovery cycle after infusion demonstrated the greatest changes post-contraction. Prominent abnormalities developed in Na(+) channel-associated parameters in response to natural activity, without significant alteration in axonal membrane potential or Na(+)/K(+) pump function. Findings from the present series suggest that oxaliplatin affects nerve excitability through voltage-dependent mechanisms, with specific effects mediated through axonal Na(+) channel inactivation.
• 0.52

  Impact points

  Reaching further with online education? The development of an effective online program in palliative oncology.

  Bogda Koczwara, Kay Francis, Franca Marine, David Goldstein, Craig Underhill, Ian Olver

  Journal of cancer education : the official journal of the American Association for Cancer Education. 09/2010; 25(3):317-23.

  Patients in rural and remote Australia have less access to specialist oncology services and rely more on local health professionals for provision of cancer care. We have developed a 7.5-h online educational program on palliative oncology for health professionals focused on the needs of rural provide... [more] Patients in rural and remote Australia have less access to specialist oncology services and rely more on local health professionals for provision of cancer care. We have developed a 7.5-h online educational program on palliative oncology for health professionals focused on the needs of rural providers. There were 501 active (enrolled) users and 268 ad hoc (non-enrolled) users, with 90 completing evaluation. Eighty-two (91%) indicated that their learning needs were partially or entirely met. Sixty-five (75%) respondents planned to review or change their practice as a result. The online program is effective in meeting learning needs of Australian health providers, reaching high numbers with high acceptability.
• 2.42

  Impact points

  A randomized controlled trial of a standardized educational intervention for patients with cancer pain.

  Melanie R Lovell, Peta M Forder, Martin R Stockler, Phyllis Butow, Esther M Briganti, Richard Chye, David Goldstein, Frances M Boyle

  Journal of pain and symptom management. 07/2010; 40(1):49-59.

  Published literature has not defined the effectiveness of standardized educational tools that can be self-administered in the general oncology population with pain. We sought to determine if an educational intervention consisting of a video and/or booklet for adults with cancer pain could improve kn... [more] Published literature has not defined the effectiveness of standardized educational tools that can be self-administered in the general oncology population with pain. We sought to determine if an educational intervention consisting of a video and/or booklet for adults with cancer pain could improve knowledge and attitudes about cancer pain management, pain levels, pain interference, anxiety, quality of life, and analgesic use. Eligible participants had advanced cancer, a pain score >/=2 of 10 in the last week, English proficiency, an estimated prognosis of more than one month, and were receiving outpatient cancer treatment at participating hospitals. Participants completed baseline assessments and then were randomly allocated to receive a booklet, a video, both, or neither, in addition to standard care. Outcome measures at two and four weeks included the Barriers Questionnaire (BQ), Brief Pain Inventory, Global Quality of Life Scale, and Hospital Anxiety and Depression Scale. Adequacy of analgesia and severity of pain were assessed with the Pain Management Index and a daily pain diary. One hundred fifty-eight participants were recruited from 21 sites over 42 months. Baseline mean barriers scores were lower than reported in previous Australian studies at 1.33 (standard deviation: 0.92). Mean average pain and worst pain scores improved significantly in patients receiving both the video and booklet by 1.17 (standard error [SE]: 0.51, P=0.02) and 1.12 (SE: 0.57, P=0.05), respectively, on a 0-10 scale. The addiction subscale of the BQ score was improved by 0.44 (SE: 0.19) for participants receiving any part of the intervention (P=0.03). Provision of a video and/or booklet for people with cancer pain was a feasible and effective adjunct to the management of cancer pain.
• 2.65

  Impact points

  Fixed-dose-rate gemcitabine combined with cisplatin in patients with inoperable biliary tract carcinomas.

  David Goldstein, M Corona Gainford, Chris Brown, Niall Tebbutt, Stephen P Ackland, Guy van Hazel, Michael Jefford, Ehtesham Abdi, Sid Selva-Nayagam, Val Gebski, Danielle Miller, Jenny Shannon

  Cancer chemotherapy and pharmacology. 05/2010; 67(3):519-25.

  Biliary tract cancers (BTC) have a poor prognosis, and there is no consensus on the best chemotherapy regimen. This study determined the response rate for fixed-dose-rate (FDR) gemcitabine combined with cisplatin. This multicentre phase II trial enrolled 50 patients with inoperable locally advanced ... [more] Biliary tract cancers (BTC) have a poor prognosis, and there is no consensus on the best chemotherapy regimen. This study determined the response rate for fixed-dose-rate (FDR) gemcitabine combined with cisplatin. This multicentre phase II trial enrolled 50 patients with inoperable locally advanced or metastatic BTC. Treatment consisted of FDR gemcitabine 1,000 mg/m² (10 mg/m²/min) and cisplatin 20 mg/m² on days 1 and 8 of a 21-day cycle. The primary endpoint was response rate. Secondary endpoints included safety, response duration (RD), progression-free (PFS) and overall survival (OS), and cancer antigen 19-9 response. Thirteen patients (26%, 95% CI 14.6-40.4) had a partial response, and 12 (24%) had stable disease. The median RD was 8.3 months (95% CI 6.91-9.99); median PFS 4 months (95% CI 2.5-6.77); and median OS 6.8 months (95% CI 5.0-8.7). Treatment was well tolerated. Grade 3 and grade 4 nausea, vomiting, and fatigue were uncommon. Thirty-eight per cent of patients discontinued treatment because of toxicity, patient or clinician preference. This treatment combination had moderate activity with acceptable toxicity, supporting previous results that this combination has a role to play. The study does not suggest that FDR gemcitabine is superior to bolus infusion.
• 4.12

  Impact points

  Adjuvant chemotherapy for early colon cancer: what survival benefits make it worthwhile?

  Prunella Blinman, Vlatka Duric, Anna K Nowak, Philip Beale, Stephen Clarke, Karen Briscoe, Adam Boyce, David Goldstein, Malcolm Hudson, Martin Stockler

  European journal of cancer (Oxford, England : 1990). 02/2010; 46(10):1800-7.

  We sought to determine the minimum survival benefits that patients judged sufficient to make adjuvant chemotherapy for early colon cancer worthwhile, factors associated with these judgments; and, to compare a self-administered questionnaire with a validated, scripted interview. One twenty three subj... [more] We sought to determine the minimum survival benefits that patients judged sufficient to make adjuvant chemotherapy for early colon cancer worthwhile, factors associated with these judgments; and, to compare a self-administered questionnaire with a validated, scripted interview. One twenty three subjects who completed adjuvant chemotherapy for early colon cancer 3-60 months earlier completed a questionnaire; 97 were randomised to complete an interview before or after the questionnaire. Preferences were elicited by the time trade-off method in 4 hypothetical scenarios. Concordance between the interview and questionnaire was assessed with the intraclass correlation coefficient (ICC). Median age was 65 years (range 19-86), 52% were female and 74% had involved lymph nodes. Over 60% of patients judged an additional 1 month beyond life expectancies of 5 years or 15 years, and an additional 1-2% beyond 5-year survival rates of 85% or 65%, sufficient to make chemotherapy worthwhile. Subjects with tertiary education (p=0.003) or aged 75 years or less (p=0.02) judged larger benefits necessary to make chemotherapy worthwhile. Concordance between the interview and questionnaire was high (ICCs 0.71-0.82). Most subjects judged small survival benefits sufficient to make adjuvant chemotherapy worthwhile. A self-administered questionnaire was a valid and acceptable way of eliciting preferences.