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BACKGROUND: This multicentre, randomised, double-blinded, placebo-controlled, phase II/III trial aimed to evaluate an oral THC:CBD (tetrahydrocannabinol:cannabidiol) cannabis extract for prevention of refractory chemotherapy-induced nausea and vomiting (CINV). Here we report the phase II component results. PATIENTS AND METHODS: Eligible patients experienced CINV during moderate-to-high emetogenic intravenous chemotherapy despite guideline-consistent antiemetic prophylaxis. Study treatment consisted of one cycle of 1-4 self-titrated capsules of oral THC 2.5 mg/CBD 2.5 mg (TN-TC11M) three times daily, from days -1 to 5, and 1 cycle of matching placebo in a crossover design, then blinded patient preference for a third cycle. The primary end point was the proportion of participants with complete response during 0-120 h from chemotherapy. A total of 80 participants provided 80% power to detect a 20% absolute improvement with a two-sided P value of 0.1. RESULTS: A total of 81 participants were randomised; 72 completing two cycles were included in the efficacy analyses and 78 not withdrawing consent were included in safety analyses. Median age was 55 years (range 29-80 years); 78% were female. Complete response was improved with THC:CBD from 14% to 25% (relative risk 1.77, 90% confidence interval 1.12-2.79, P = 0.041), with similar effects on absence of emesis, use of rescue medications, absence of significant nausea, and summary scores for the Functional Living Index-Emesis (FLIE). Thirty-one percent experienced moderate or severe cannabinoid-related adverse events such as sedation, dizziness, or disorientation, but 83% of participants preferred cannabis to placebo. No serious adverse events were attributed to THC:CBD. CONCLUSION: The addition of oral THC:CBD to standard antiemetics was associated with less nausea and vomiting but additional side-effects. Most participants preferred THC:CBD to placebo. Based on these promising results, we plan to recruit an additional 170 participants to complete accrual for the definitive, phase III, parallel group analysis. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12616001036404; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370473&isReview=true.

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BACKGROUND: We sought to determine whether the substantial benefits of topical nitroglycerin with first-line, platinum-based, doublet chemotherapy in advanced nonsmall-cell lung cancer (NSCLC) seen in a phase II trial could be corroborated in a rigorous, multicenter, phase III trial. PATIENTS AND METHODS: Patients starting one of five, prespecified, platinum-based doublets as first-line chemotherapy for advanced NSCLC were randomly allocated treatment with or without nitroglycerin 25 mg patches for 2 days before, the day of, and 2 days after, each chemotherapy infusion. Progression-free survival (PFS) was the primary end point. RESULTS: Accrual was stopped after the first interim analysis of 270 events. Chemotherapy was predominantly with carboplatin and gemcitabine (79%) or carboplatin and paclitaxel (18%). The final analysis included 345 events in 372 participants with a median follow-up of 33 months. Topical nitroglycerin had no demonstrable effect on PFS [median 5.0 versus 4.8 months, hazard ratio (HR) = 1.07, 95% confidence interval (CI) 0.86-1.32, P = 0.55], overall survival (median 11.0 versus 10.3 months, HR = 0.99, 95% CI 0.79-1.24, P = 0.94), or objective tumor response (31% versus 30%, relative risk = 1.03, 95% CI 0.82-1.29, P = 0.81). Headache, hypotension, syncope, diarrhea, dizziness, and anorexia were more frequent in those allocated nitroglycerin. CONCLUSION: The addition of topical nitroglycerin to carboplatin-based, doublet chemotherapy in NSCLC had no demonstrable benefit and should not be used or pursued further. CLINICAL TRIALS NUMBER: Australian New Zealand Clinical Trials Registry Number ACTRN12608000588392.

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BACKGROUND: Docetaxel (Taxotere) improve survival and prostate-specific antigen (PSA) response rates in patients with metastatic castrate-resistant prostate cancer (CRPC). We studied the combination of PI-88, an inhibitor of angiogenesis and heparanase activity, and docetaxel in chemotherapy-naive CRPC. PATIENTS AND METHODS: We conducted a multicentre open-label phase I/II trial of PI-88 in combination with docetaxel. The primary end point was PSA response. Secondary end points included toxicity, radiologic response and overall survival. Doses of PI-88 were escalated to the maximum tolerated dose; whereas docetaxel was given at a fixed 75 mg/m(2) dose every three weeks RESULTS: Twenty-one patients were enrolled in the dose-escalation component. A further 35 patients were randomly allocated to the study to evaluate the two schedules in phase II trial. The trial was stopped early by the Safety Data Review Board due to a higher-than-expected febrile neutropenia of 27%. In the pooled population, the PSA response (50% reduction) was 70%, median survival was 61 weeks (6-99 weeks) and 1-year survival was 71%. CONCLUSIONS: The regimen of docetaxel and PI-88 is active in CRPC but associated with significant haematologic toxicity. Further evaluation of different scheduling and dosing of PI-88 and docetaxel may be warranted to optimise efficacy with a more manageable safety profile.

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International research suggests complementary therapy usage is common in women with breast cancer. Comparable data do not exist for Australia. A self-completed questionnaire was used to survey Australian women with breast cancer about their usage of complementary therapies. The survey was mailed to members of two breast cancer consumer advocacy groups, and assessed type of therapy used, reasons for use, and sources of information about complementary therapies. Of 367 respondents with breast cancer, 87.5% had used complementary therapies, with many using four or more therapies. Most commonly used were vitamin supplements (54.2%), support groups (49.8%), massage (41.4%) and meditation (38.7%). Common reasons for use included improving physical (86.3%) and emotional (83.2%) wellbeing and boosting the immune system (68.8%). Women sought information about complementary therapies from a variety of sources. The range of therapies used and the diverse reasons for use emphasise the need for reliable, evidence-based information about complementary therapies for women and clinicians.

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BACKGROUND: Oral capecitabine achieves a superior response rate with an improved safety profile compared with bolus 5-fluorouracil-leucovorin (5-FU/LV) as first-line treatment for patients with metastatic colorectal cancer. We report here the results of a large phase III trial investigating adjuvant oral capecitabine compared with 5-FU/LV (Mayo Clinic regimen) in Dukes' C colon cancer. PATIENTS AND METHODS: Patients aged 18-75 years with resected Dukes' C colon carcinoma were randomized to receive 24 weeks of treatment with either oral capecitabine 1250 mg/m(2) twice daily, days 1-14 every 21 days (n = 993), or i.v. bolus 5-FU 425 mg/m(2) with i.v. leucovorin 20 mg/m(2) on days 1-5, repeated every 28 days (n = 974). RESULTS: Patients receiving capecitabine experienced significantly (P <0.001) less diarrhea, stomatitis, nausea/vomiting, alopecia and neutropenia, but more hand-foot syndrome than those receiving 5-FU/LV. Fewer patients receiving capecitabine experienced grade 3 or 4 neutropenia, febrile neutropenia/sepsis and stomatitis (P <0.001), although more experienced grade 3 hand-foot syndrome than those treated with 5-FU/LV (P <0.001). Capecitabine demonstrates a similar, favorable safety profile in patients aged <65 years or > or = 65 years old. CONCLUSIONS: Based on its improved safety profile, capecitabine has the potential to replace 5-FU/LV as standard adjuvant treatment for patients with colon cancer. Efficacy results are expected to be available in Keywords: Adjuvant treatment, capecitabine, chemotherapy, colorectal cancer

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Ehlers-Danlos syndrome (EDS) is a collection of inherited connective tissue disorders with at least 10 types, differentiated on clinical and genetic grounds. Malignancy has been described only rarely in association with the syndrome. Epithelioid hemangioendothelioma (EH) is a rare endothelial tumor, which displays clinical behavior intermediate between that of hemangioma and angiosarcoma. A case report of a 50-year-old man with type IV EDS who was extensively investigated for several years for multiple mediastinal nerve palsies and chest pain. Magnetic resonance imaging (MRI) demonstrated an anterior mediastinal mass, which at biopsy showed EH. Subsequent metastatic spread to liver and lungs is unique among reported cases of mediastinal EH. The patient experienced significant symptomatic improvement from external beam radiotherapy (RT) to the mediastinum. After metastatic disease developed, multiagent chemotherapy was administered, but without response. The literature is reviewed regarding treatment of EH and the potential problems associated with EDS. Although there appears to be no etiological association between EDS and EH, the connective tissue disease clearly contributed to a delay in diagnosis and raised concerns regarding RT tolerance. The potential predisposition to aggressive tumor invasion remains a possibility. In addition, mediastinal EH has the potential to metastasize, and in this case demonstrated resistance to a broad range of chemotherapy agents.

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OBJECTIVE: To assess the patterns of alternative medicine use in patients of a public hospital oncology unit, and to compare patients' experience of alternative with conventional medicine. DESIGN AND SETTING: Self-administered questionnaire survey of cancer patients attending specialist consulting rooms at the Royal North Shore Hospital and the Oncology Outpatient Clinic at Port Macquarie Base Hospital during August 1995. PARTICIPANTS: 507 patients attended the clinics; 335 (66%) returned questionnaires, of which 319 (62%) were sufficiently complete for analysis. MAIN OUTCOME MEASURES: Expectations of and satisfaction with both conventional and alternative treatment, use of alternative treatment, and patient characteristics associated with this use. RESULTS: Expectations of and satisfaction with both conventional and alternative treatment were very high. Alternative treatments (most commonly dietary and psychological methods) were used by 21.9% of patients. Median annual cost of alternative therapy was $530, with most patients reporting "value for money". Younger age and being married were positively associated, and satisfaction with conventional treatment was negatively associated, with alternative medicine use; 40% of patients did not discuss alternative medicine with their physician. CONCLUSIONS: A significant proportion of cancer patients use one or more forms of alternative therapy. The use of alternative therapy may reflect on deficiencies in the current standard of care.

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A policy of palliative intent thoracic irradiation was prospectively evaluated in 38 consecutive patients referred for treatment of inoperable non-small cell lung cancer at a single institution. A target dose of 1700 cGy in two fractions 1 week apart was delivered. Characteristics of the treatment group revealed most (87%; 33/38) to be of good-excellent performance status with minimal weight loss before irradiation. Although three patients (8%) had initial metastatic disease, all had symptoms referable to the thorax with cough (71%), dyspnoea (55%), haemoptysis (39%), and chest wall pain (34%) being dominant. Following treatment, the relative risk of maintaining complete response with regard to each of these symptoms was 0.91, 0.40, 0.92 and 0.78, respectively. Overall 70% of patients maintained complete symptomatic response to time of death or last review. Uncorrected median survival was 35 weeks and was comparable to best international end-results for either palliative intent or curative intent radiation schedules. We conclude that the radiation regimen employed is safe, efficacious and eminently resource conscious. Recognition of patient groups who overwhelmingly derive no benefit from conventional fractionation schedules will streamline access to radiotherapy services of patients suitable for radical treatment.

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A 47-year-old woman developed pulmonary eosinophilia from the use of maloprim as malaria prophylaxis. The diagnosis was confirmed by bronchoalveolar lavage (BAL) and transbronchial lung biopsy. Her condition improved with drug withdrawal and steroid therapy. With the increased use of pyrimethamine and dapsone in the treatment of human immunodeficiency syndrome (HIV) infection, this form of drug allergy may become more common.

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