Shawgi Sukumaran

A phase I study to determine the safety, tolerability and maximum tolerated dose of green-lipped mussel (Perna canaliculus) lipid extract, in patients with advanced prostate and breast cancer

BACKGROUND This was a phase I trial to determine the maximum tolerated dose (MTD) of a marine lipid extract from the New Zealand green-lipped mussel (Perna canaliculus), as an inhibitor of 5- and 12-lipo-oxygenase enzymes, in patients with advanced breast and prostate cancers. PATIENTS AND METHODS This was an open-labelled, phase I, dose-escalation study. Proprietary form of green-lipped mussel lipid extract (GLMLE), 260-mg capsule, was administered on a twice-daily schedule, orally. Patients remained on study until disease progression or unacceptable toxicity. RESULTS From December 1999 to May 2003, 17 patients were enrolled. Fifteen of them were male with advanced prostate cancer and two were female with advanced breast cancer. The median age of the patients was 74 years (range 56-85 years). Sixteen patients were assessable for adverse events and dose-limiting toxicity (DLT). Reason for withdrawal from the study included progressive disease (n = 12), death (n = 1) and DLT (n = 3). Two patients had evidence of grade 4 hepatic dysfunction. The MTD was not reached. There were no objective tumour responses noted. CONCLUSIONS GLMLE appears to be a well-tolerated compound in this setting. There appears to be no objective benefit. However, grade 3/4 hepatic toxicity noted in two patients is of concern and should be considered while evaluating patients taking GLMLE or while designing studies with this agent.

Returning to work following curative chemotherapy: a qualitative study of return to work barriers and preferences for intervention

PurposeThis study aimed to explore barriers to return to work (RTW) and preferences for intervention and support for cancer patients treated with curative intent from the perspectives of cancer survivors and oncology health professionals.MethodsParticipants attended a focus group (N = 24) or an individual interview (N = 14). A topic guide and a semi-structured recorded interview format were used to gather data, which were later transcribed and analysed for global themes and subthemes.ResultsWith regard to barriers, the global theme ‘work capacity’ captured an array of barriers encompassing financial pressure, preparedness for work, lack of confidence as well as other key physical, practical and psychosocial barriers. Participants expressed a preference for RTW models that focus on objective and structured assessment whilst allowing for flexibility to address individual needs.ConclusionsCancer survivors perceive multiple barriers when attempting to RTW. These barriers were perceived to impact upon work capacity, where ‘capacity’ was defined broadly to include practical, physical and psychosocial concerns. RTW is an important concern for cancer survivors and structured RTW interventions should be incorporated into the care of cancer survivors.

Is self-management feasible and acceptable for addressing nutrition and physical activity needs of cancer survivors?

Self‐management is recommended for patients with chronic conditions, but its use with cancer survivors is underexplored. Optimal strategies for achieving lifestyle changes in cancer survivors are not known.

Reversing Hyperammonemia in Neuroendocrine Tumors.

Ammonia is a neurotoxin that is normally cleared by the intact liver and if not, hyperammonemia results in hepatic encephalopathy. Hyperammonemia may be owing to primary or secondary causes. Early diagnosis is important to prevent permanent brain damage. Advanced malignancy involving the liver is associated with hyperammonemia as a result of abnormality of the portal venous system or massive hepatic tumor burdon. Neuroendocrine tumors are an example of a malignant process that frequently involves the liver but despite this, may still have a relatively good prognosis, and are often characterized by chronic manageable symptoms and slow progression. Hyperammonemia in neuroendocrine tumor would represent a potentially reversible but ongoing process associated with an indolent malignancy. We present 2 cases that are examples of this diagnosis and discuss the diagnostic and management issues that may arise.

Small cell lung cancer: patterns of care and their influence on survival - 25 years experience of a single Australian oncology unit.

Aim:  Evidence supporting improved outcomes for small cell lung cancer (SCLC) in recent decades is limited. This study aimed to identify patterns of care and survival over two time periods; 1 January 1987 to 31 December 1996 (cohort A) and 1 January 1997 to 31 December 2006 9 (cohort B).

Pre-treatment serum lactate dehydrogenase as a biomarker in small cell lung cancer

Small cell lung cancer is a rapidly progressive disease with high fatality. No sensitive and specific biomarker to assist in managing this disease exists currently.

Goserelin Toxicities and Preferences for Ovarian Suppression Method in Pre-menopausal Women with Breast Cancer.

Goserelin, a form of medical ovarian suppression, is an effective treatment for pre‐menopausal women with breast cancer (PMBC). Meta‐analysis data showed that similar efficacy is achieved with medical ovarian suppression and non‐pharmacological ovarian suppression (NPOS) – oophorectomy or ovarian irradiation. The acceptance rate of NPOS remains low.

Pregnancy screening prior to chemotherapy administration

A retrospective case notes review was performed to determine compliance with screening for undetected pregnancy prior to commencement of chemotherapy at Flinders Medical Centre. All female patients aged 18–55 who commenced chemotherapy between January and December 2014 were included. During the first 12 months, for women identified as having childbearing potential, pre‐chemotherapy pregnancy screening was performed only in 40% of patients under 40 years and in 20.5% of the entire age range.

Delayed onset of benign pleural effusion following concurrent chemoradiotherapy for inoperable non-small-cell lung cancer.

Chronic benign pleural effusion (BPE) is a rare complication of concurrent chemoradiotherapy (CRT) for inoperable stage IIIA non‐small‐cell lung cancer (NSCLC). This report presents three cases of BPE, the workup to differentiate this benign condition from recurrence of cancer and recommends a pleural biopsy as part of the diagnostic process. These inflammatory exudates often remain indolent, and may not require drainage or surgical intervention. In the absence of clinical, radiological and pathological evidence of recurrent disease, we recommend clinicians manage these patients expectantly, using regular clinical assessment and imaging.

Abstract A107: Clinical trial combining proteasome (NPI‐0052) and HDAC (vorinostat) inhibition in melanoma, pancreatic, and lung cancer

Background: Combining proteasome inhibition with HDAC inhibition has recently been shown to provide synergistic anti‐tumor activity in preclinical and clinical studies. A proposed mechanism centers around inhibition of both of the major protein disposal mechanisms of the cell, resulting in near complete lack of ability of the tumor to dispose of normal pro‐apoptotic and growth inhibitory peptides. The bi‐cyclic structure of NPI‐0052 is not polypeptide based as are other proteasome inhibitors, leading to rapid, broad and prolonged inhibition of all 3 proteolytic sites, with unique proteasome inhibition, toxicology and efficacy profiles. Preclinical studies indicated marked synergy with a number of HDAC inhibitors in solid tumor and hematologic malignancy models. Materials and Methods: Patients with melanoma, pancreatic carcinoma and NSCLC having failed standard therapies were given NPI‐0052 intravenously on a weekly (Days 1, 8 and 15) schedule dose escalation, in combination with vorinostat 300 mg orally on the first 16 days of each 28 day cycle. A 3+3 design was used with the dose of NPI‐0052 escalated from 0.15 mg/m2 to 0.7 mg/m2. In addition to standard safety laboratory studies, proteasome inhibition and pharmacokinetics are also assayed in blood on Day 1 and multiple subsequent time points. Results: 20 patients have been enrolled into this study. There has not been an indication of increased toxicity with the combination, and the dose of NPI‐0052 has been escalated to and is currently being administered at the full single agent dose without dose limiting toxicity. Pharmacokinetic data indicate a short half life of NPI‐0052 ( Conclusions: The combination of full dose NPI‐0052 with vorinostat is tolerable and has not resulted in unexpected safety findings (of note the toxicity profile is dissimilar to that reported with other proteasome inhibitors, in not inducing neutropenia, thrombocytopenia or peripheral neuropathy). Pharmacokinetic and pharmacodynamic results were likewise consistent with what are expected from prior data with each drug. Enrollment continues to further characterize the combination at the recommended phase 2 dose. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A107.