Zarnie Lwin

Interleukin-6: An angiogenic target in solid tumours

During the past decade, incorporating anti-angiogenic agents into the therapeutic management of a myriad of malignancies has in certain cases made a significant impact on survival. However, the development of resistance to these drugs is inevitable and swift disease progression on their cessation often ensues. Hence, there is a drive to devise strategies that aim to enhance response to anti-angiogenic therapies by combining them with other targeted agents that facilitate evasion from resistance. The pleiotropic cytokine, interleukin-6 (IL-6), exerts pro-angiogenic effects in the tumour microenvironment of several solid malignancies and there is emerging evidence that reveals significant relationships between IL-6 signalling and treatment failure with antibodies directed against vascular endothelial growth factor (VEGF). This review summarises the role of IL-6 in pivotal angiogenic processes and preclinical/clinical research to support the future introduction of anti-IL-6 therapies to be utilised either in combination with other anti-angiogenic drugs or as a salvage therapy for patients with diseases that become refractory to these approaches.

The continuing role of chemotherapy for advanced non-small cell lung cancer in the targeted therapy era

There have been remarkable advances in the targeted treatment of advanced non-small cell lung cancer (NSCLC) over the past several years. Survival outcomes are steadily improving as management paradigms shift in the diagnosis and treatment of advanced NSCLC. Customizing treatment based on histology and molecular typing has become a standard of care in this era of targeted therapy. While new chemotherapeutic agents have proven effective, the pivotal role of platinum-based chemotherapy doublets has been confirmed. Maintenance chemotherapy has become an option, but who to employ it in remains unclear in the real-world setting. Efforts to overcome resistance to targeted agents are ongoing utilizing combination regimens of chemotherapy plus targeted agents, but optimizing combination strategies needs further exploration. This review highlights recent developments in novel chemotherapeutics and in chemotherapy strategies over the past two years. Despite advances in molecular medicine, there remains an essential role for chemotherapy in advanced NSCLC, even in the recent targeted therapy era.

Negotiating palliative care in the context of culturally and linguistically diverse patients

There is an increasing emphasis on meeting the healthcare needs of culturally and linguistically diverse (CALD) communities in Australia. Negotiating the point of futility and the transition to specialist palliative care requires not only effective communication but also sensitivity to cultural and linguistic specificities. This can be a challenging process for clinicians, patients and families. Here, we outline some of the key challenges currently facing many clinicians in the context of CALD patients, with particular reference to the transitioning of patients to specialist palliative care. We suggest a focus on further research that can systematically document and model existing CALD‐specific clinical processes and pathways, which can then support the development of targeted educational interventions. This includes developing a multi‐stakeholder understanding of the CALD experience that moves beyond cultural stereotyping and predicting need.

Economic evaluation of docetaxel for breast cancer

Breast cancer is among the leading causes of cancer morbidity worldwide and accounts for a significant proportion of overall healthcare costs. Cost-effectiveness and cost-utility evaluations of therapy provide insight into the societal value of different treatments, helping decision-makers to prioritize resource allocation and maximize benefit in cancer control within resource constraints. Docetaxel, a plant alkaloid of the taxane group, has been recognized as a highly active chemotherapy agent in breast, lung and prostate cancers, among others. In the last decade, docetaxel has become incorporated into the neoadjuvant, adjuvant and metastatic treatment of breast cancer. This article reviews the economic data supporting the use of docetaxel in the treatment of breast cancer.

Safety, Pharmacokinetics and Antitumor Response of Depatuxizumab Mafodotin as Monotherapy or in Combination with Temozolomide in Patients with Glioblastoma

Background We recently reported an acceptable safety and pharmacokinetic profile of depatuxizumab mafodotin (depatux-m), formerly called ABT-414, plus radiation and temozolomide in newly diagnosed glioblastoma (arm A). The purpose of this study was to evaluate the safety and pharmacokinetics of depatux-m, either in combination with temozolomide in newly diagnosed or recurrent glioblastoma (arm B) or as monotherapy in recurrent glioblastoma (arm C). Methods In this multicenter phase I dose escalation study, patients received depatux-m (0.5-1.5 mg/kg in arm B, 1.25 mg/kg in arm C) every 2 weeks by intravenous infusion. Maximum tolerated dose (MTD), recommended phase II dose (RP2D), and preliminary efficacy were also determined. Results Thirty-eight patients were enrolled as of March 1, 2016. The most frequent toxicities were ocular, occurring in 35/38 (92%) patients. Keratitis was the most common grade 3 adverse event observed in 6/38 (16%) patients; thrombocytopenia was the most common grade 4 event seen in 5/38 (13%) patients. The MTD was set at 1.5 mg/kg in arm B and was not reached in arm C. RP2D was declared as 1.25 mg/kg for both arms. Depatux-m demonstrated a linear pharmacokinetic profile. In recurrent glioblastoma patients, the progression-free survival (PFS) rate at 6 months was 30.8% and the median overall survival was 10.7 months. Best Response Assessment in Neuro-Oncology responses were 1 complete and 2 partial responses. Conclusion Depatux-m alone or in combination with temozolomide demonstrated an acceptable safety and pharmacokinetic profile in glioblastoma. Further studies are currently under way to evaluate its efficacy in newly diagnosed (NCT02573324) and recurrent glioblastoma (NCT02343406).

Neutrophil–lymphocyte ratio dynamics during concurrent chemo-radiotherapy for glioblastoma is an independent predictor for overall survival

Elevated neutrophil–lymphocyte ratio (NLR) may predict worse outcomes in cancer, including glioblastoma (GBM). This study assessed whether change in NLR during focal radiotherapy and concomitant temozolomide (RT-TMZ) provides further prognostic information. This was a retrospective review of patients treated with RT-TMZ for histologically confirmed GBM from January 2004 to September 2010. Variables assessed included age, ECOG performance status (PS), dexamethasone use and extent of surgery. Hematological results were collected at baseline, during and 4 weeks post RT-TMZ. Kaplan–Meier method was used to calculate overall survival (OS). Multivariable analysis (MVA) assessed for joint effect of covariates on OS and Pearson Correlation Coefficients assessed for association between dexamethasone dose and NLR change. With a median age of 55 (range 18–70), 369 patients were included. Median follow up was 15.1 month (range 1.6–134.6). The OS was 66.1% (95% CI 61.2–70.6) and 31.4 (95% CI 26.8–36.1) at 1 and 2 years, respectively. On univariate analysis, both decrease in NLR post RT-TMZ (HR 0.641, p < 0.0001) and baseline NLR < 7.5 (HR 0.628, p < 0.0001) were associated with longer OS. On MVA decrease in NLR (HR 0.727, 95% CI 0.578–0.915), age (HR 1.025, 95% CI 1.012–1.038), baseline neutrophil (<8) (HR 0.689, 95% CI 0.532–0.891), total TMZ cycles (HR 0.89, 95% CI 0.867–0.913) and PS (HR 0.476, 95% CI 0.332–0.683) were independent predictors of OS. These findings suggest that a decrease in NLR during RT-TMZ, accounting for known prognostic factors, is an independent prognostic factor for survival in GBM.

Low-grade oligodendroglioma: current treatments and future hopes

Current treatment modalities for low-grade gliomas include surgery, radiotherapy and chemotherapy. Management of these ultimately incurable tumors remains controversial, particularly the timing and extent of surgery, and the optimal sequence of radiotherapy and chemotherapy thereafter. Two ongoing Phase III trials should provide definitive answers to some of these controversial issues in the treatment of low-grade gliomas and confirm the impact of molecular predictors of response and outcome. This review will discuss recent progress and topical issues in the treatment of low-grade gliomas.

The Social Reception of Women With Cancer

Experiences of cancer are enmeshed with cultural understandings and social discourses around responsibility and causation. A cancer diagnosis can raise questions about its causation—including the role of the individual—whereas the disease and its treatment provide various social markers of illness. We present a sociological study of 81 women’s accounts of living with cancer, with a focus on how women interpret their illness, in light of their interpersonal interactions and accounts of social relations. Our analysis reveals women’s experiences of cancer diagnosis and treatment, the varied sociocultural meanings of cancer and the responses it elicits, the presence of moral assessments within everyday interactions, and the implications for the support and care they receive. We argue that the experience of cancer should be seen as intimately interwoven with its social reception and cultural sense-making practices, including normative constructs which promote ideas about (in)justice, responsibilization, and shame.

Experiences of interpreters in supporting the transition from oncology to palliative care: A qualitative study

Medical consultations focused on managing the transition to palliative care are interpersonally challenging and require high levels of communicative competence. In the context of non‐English speaking patients, communication challenges are further complicated due to the requirement of interpreting; a process with the potential to add intense layers of complexity in the clinical encounter, such as misunderstanding, misrepresentation and power imbalances. The aim of the study was to explore the experiences and perspectives of professional interpreters in supporting the transition of culturally and linguistically diverse patients to specialist palliative care.

Involvement of low- and middle-income countries in randomized controlled trial publications in oncology

BackgroundWe describe trends in participation by investigators from low- and middle-income countries (LMCs) in publications describing oncology randomized control trials (RCTs) over a decade.MethodsWe used Medline to identify RCTs published in English from 1998 to 2008 evaluating treatment in lung, breast, colorectal, stomach and liver cancers. Data on author affiliations, authorship roles, trial characteristics, funding and interventions were extracted from each article. Countries were stratified as low-, middle- or high-income using World Bank data. Interventions were categorized as requiring basic, limited, enhanced or maximal resources as per the Breast Health Global Initiative classification. Logistic regression was used to identify factors associated with authorship by investigators from LMCs.Results454 publications were identified. Proportion of articles with at least one LMC author increased over time from 20% in 1998 to 29% in 2008 (p = 0.01), but almost all LMC authors were from middle-income countries. Proportion of articles with at least one LMC author was higher among articles that explicitly reported recruitment in at least one LMC vs those that did not (76% vs 13%). Among 87 articles (19%) that involved authors from LMCs, 17% had LMC authors as first or corresponding authors, and 67% evaluated interventions requiring enhanced or maximal resources. Factors associated with LMC authorship included industry funding (OR = 3.54, p = 0.0001), placebo comparator arm (OR = 2.57, p = 0.02) and palliative intent treatment (OR = 4.00, p = 0.0003).ConclusionAn increasing number of publications describing oncology RCTs involve authors from LMC countries but primarily in non-leadership roles in industry-funded trials.