Audits of oncology units - an effective and pragmatic approach.

BACKGROUND: Audits of oncology units are part of all quality-assurance programmes. However, they do not always come across as pragmatic and helpful to staff. OBJECTIVE: To report on the results of an online survey on the usefulness and impact of an audit process for oncology units. METHODS: Staff in oncology units who were part of the audit process completed the audit self-assessment form for the unit. This was followed by a visit to each unit by an assessor, and then subsequent personal contact, usually via telephone. The audit self-assessment document listed quality-assurance measures or items in the physical and functional areas of the oncology unit. There were a total of 153 items included in the audit. The online survey took place in October 2016. The invitation to participate was sent to 59 oncology units at which staff members had completed the audit process. RESULTS: The online survey was completed by 54 (41%) of the 132 potential respondents. The online survey found that the audit was very or extremely useful in maintaining personal professional standards in 89% of responses. The audit process and feedback was rated as very or extremely satisfactory in 80% and 81%, respectively. The self-assessment audit document was scored by survey respondents as very or extremely practical in 63% of responses. The feedback on the audit was that it was very or extremely helpful in formulating improvement plans in oncology units in 82% of responses. Major and minor changes that occurred as a result of the audit process were reported as 8% and 88%, respectively. CONCLUSION: The survey findings show that the audit process and its self- assessment document meet the aims of being helpful and pragmatic.

Vandetanib plus pemetrexed for the second-line treatment of advanced non-small-cell lung cancer: a randomized, double-blind phase III trial.

PURPOSE: Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. This randomized, placebo-controlled phase III study assessed the efficacy of vandetanib plus pemetrexed as second-line therapy in advanced non-small-cell lung cancer. PATIENTS AND METHODS: Patients (N = 534) were randomly assigned to receive vandetanib 100 mg/d plus pemetrexed 500 mg/m(2) every 21 days (n = 256) or placebo plus pemetrexed (n = 278). Progression-free survival (PFS) was the primary end point; overall survival, objective response rate, disease control rate, time to deterioration of symptoms, and safety were secondary assessments. RESULTS: There was no significant difference in PFS between treatment arms (hazard ratio [HR], 0.86; 97.58% CI, 0.69 to 1.06; P = .108). Overall survival was also not significantly different (HR, 0.86; 97.54% CI, 0.65 to 1.13; P = .219). Statistically significant improvements in objective response rate (19% v 8%; P < .001) and time to deterioration of symptoms (HR, 0.71; P = .0052; median, 18.1 weeks for vandetanib and 12.1 weeks for placebo) were observed in patients receiving vandetanib. Adding vandetanib to pemetrexed increased the incidence of some adverse events, including rash, diarrhea, and hypertension, while showing a reduced incidence of nausea, vomiting, anemia, fatigue, and asthenia with no reduction in the dose intensity of pemetrexed. CONCLUSION: This study did not meet the primary end point of statistically significant PFS prolongation with vandetanib plus pemetrexed versus placebo plus pemetrexed. The vandetanib combination showed a significantly higher objective response rate and a significant delay in the time to worsening of lung cancer symptoms versus the placebo arm as well as an acceptable safety profile in this patient population.

A randomized, double-blind, placebo-controlled phase II study of vandetanib plus docetaxel/prednisolone in patients with hormone-refractory prostate cancer.

Vandetanib (ZACTIMA) is a once-daily oral anticancer drug that selectively inhibits vascular endothelial growth factor receptor, epidermal growth factor receptor, and rearranged during transfection signaling. This randomized (1:1), double-blind study evaluated vandetanib (100 mg/day) or placebo in combination with docetaxel (D; 75 mg/m(2) every 3 weeks) and prednisolone (P; 2 x 5 mg/day) in 86 patients with metastatic hormone-refractory prostate cancer (mHRPC). The primary assessment was prostate-specific antigen (PSA) response (confirmed reduction of >or=50% from baseline) and a greater number of patients showed a PSA response with placebo + DP (67%) versus vandetanib + DP (40%); hazard ratio = 2.23 (one-sided 80% confidence limit = 2.90; one-sided p = 0.99). More patients experienced progression events (disease progression or death from any cause) with vandetanib + DP (65%) versus placebo + DP (60%); hazard ratio = 1.13 (one-sided 80% confidence limit = 1.44; one-sided p = 0.67). The overall incidence of adverse events was similar in both groups, although more patients experienced adverse events, leading to permanent discontinuation with vandetanib + DP (28%) versus placebo + DP (12%). However, the safety and tolerability profile for vandetanib was similar to that previously reported; adverse events that occurred more frequently in the vandetanib + DP arm were hypertension (14% vs. 2%), erythematous rash (14% vs. 2%), and exfoliative rash (12% vs. 2%). In this study of patients with mHRPC, vandetanib + DP did not demonstrate any efficacy benefit, compared with placebo + DP.

Phase II study of oral vinorelbine in combination with carboplatin followed by consolidation therapy with oral vinorelbine as single-agent in unresectable localized or metastatic non-small cell lung carcinoma.

INTRODUCTION: This phase II study assessed the efficacy and safety of oral vinorelbine given weekly in combination with carboplatin (CBDCA) AUC 5 once every 3 weeks for four cycles in chemonaive patients with advanced non-small cell lung carcinoma (NSCLC), followed by consolidation therapy with single-agent oral vinorelbine in non-progressive patients. METHODS: Chemonaive advanced NSCLC patients received four cycles of combination therapy with CBDCA AUC 5 day 1 and oral vinorelbine, 60 mg/m2 on days 1, 8 and 15 (cycle 1), dose increased to 80 mg/m2 (cycles 2-4) in absence of grades 3-4 neutropenia (NCI-CTCv2). Consolidation therapy with oral vinorelbine was continued (cycle 5) at same dosage; if dose was decreased during combination therapy, it was given at 60 mg/m2, then increased at 80 mg/m2 (cycle 6) in absence of grades 3-4 neutropenia until PD, toxicity or patient's refusal. RESULTS: A total of 57 patients were registered and 56 patients were treated (ITT population), median age was 61 years (37-71). Objective response evaluated by RECIST was 17.9% (95% confidence interval, CI [8.9-30.4]) and disease control (CR, PR, NC) 73.2% (95% CI [59.7-84.2]), median progression-free survival 4.3 months (95% CI [3.1-5.1]) with median overall survival 9.7 months (95% CI [7.7-11.9]) and 1-year survival 37.1% (95% CI [24.4, 49.9]). Grades 3-4 neutropenia occurred in 67.9% of patients during combination and 20% during consolidation; febrile neutropenia occurred in 4 patients (7.1%) during combination therapy. Non-hematological toxicities occurred primarily during combination (grade 3 nausea and grade 3 vomiting in 7.1% of patients). CONCLUSIONS: The combination of oral vinorelbine given weekly in 3-week cycles in combination with carboplatin followed by consolidation therapy with oral vinorelbine as a single-agent was able to achieve efficacy results in line with other doublets including carboplatin in terms of response as well as survival. This regimen reported a good profile of tolerability in the treatment of advanced NSCLC, allowing that this combination can be easily proposed for the palliative care of NSCLC patients where the advantages of carboplatin over cisplatin are still appreciated.

Part II: Cancer in Indigenous Africans--causes and control.

Africa has contributed substantial knowledge to the understanding of certain risk factors for cancer, such as the role of several infectious agents (eg, viruses, bacteria, and parasites), aflatoxins, and certain lifestyle factors. Although the relative importance of many lifestyle factors is becoming better understood in developed countries, more work is needed to understand the importance of these factors in different African settings. In view of the substantial genetic diversity in Africa, it would be prudent not to generalize too widely from one place to the next. We argue that risks for several exposures related to certain cancers differ from the patterns seen in developed countries. In this paper, we review the current knowledge of causes of some of the leading cancers in Africa, namely cancers of the cervix, breast, liver, prostate, stomach, bladder, and oesophagus, Kaposi's sarcoma, non-Hodgkin lymphoma, and tobacco-related cancers. There are no comprehensive cancer-control programmes in Africa and provision of radiotherapy, chemotherapy, and palliation is inadequate. Certain cost-effective interventions, such as tobacco control, provision of antiretroviral therapy, and malarial and bilharzial control, can cause substantial decreases in the burden of some of these cancers. Vaccinations against hepatitis B and oncogenic human papilloma viruses can make the biggest difference, but very few countries in Africa can afford these vaccines without substantial subsidization.

Part I: Cancer in Indigenous Africans--burden, distribution, and trends.

Cancer is an under-emphasised issue in Africa, partly because of the overwhelming burden of communicable diseases. However cancer is a common disease in Africa with 650 000 people, of a population of 965 million, diagnosed annually. Furthermore, the lifetime risk in females (between 0 and 64 years) of cancer is about 10%, which is only about 30% lower than the risk in developed countries. In females, the lifetime risk of dying from cancer in Africa is almost double the risk in developed countries. This Review is the first of two papers and focuses on the current knowledge of the distribution and trends of the most common cancers in Africa. The cancers with the highest incidence are cervical, breast, and now HIV-associated Kaposi's sarcoma. The top five cancers in males--Kaposi's sarcoma (constituting 12.9% of all cancers in males) and cancer of the liver (14.8%), prostate (9.5%), bladder (6.1%), and non-Hodgkin lymphoma (5.7%)--and in females--cancer of the cervix (constituting 23.3% of all cancers in females) and breast (19.2%), Kaposi's sarcoma (5.1%), cancer of the liver (5.0%), and non-Hodgkin lymphoma (3.7%)--are discussed in detail. The second paper will focus on the causes and control of cancer in Africa. The cancer burden in Africa is likely to increase as a result of increases in HIV-associated cancers, changes in lifestyles associated with economic development, and the increasing age of the population (despite AIDS). Although the knowledge of cancer in this region is improving, better surveillance of cancer incidence, mortality, and prevalence of risk factors is urgently needed to monitor the development of the cancer epidemic, formulate appropriate cancer-control strategies, and assess the outcomes of these strategies.

Lung cancer management in limited resource settings: guidelines for appropriate good care.

Lung cancer is a major cause of cancer death worldwide and is becoming an increasing problem in developing countries. It is important that, in countries where health care resources are limited, these resources are used most effectively and cost-effectively. The authors, with the support of the International Atomic Energy Agency, drew on existing evidence-based clinical guidelines, published systematic reviews and meta-analyses, as well as recent research publications, to summarise the current evidence and to make broad recommendations on the non-surgical treatment of patients with lung cancer. Tables were constructed which summarise the different treatment options for specific groups of patients, the increase in resource use for and the likely additional clinical benefit from each option. These tables can be used to assess the cost-effectiveness and appropriateness of different interventions in a particular health care system and to develop local clinical guidelines.

Does the tumor microenvironment influence radiation-induced apoptosis?

UNLABELLED: Cytotoxic anti-cancer agents induce apoptosis in tumor and normal tissues. Therefore, it is important to investigate which factors determine these apoptotic processes and hence their likely impact on therapeutic gain. Radiation-induced apoptosis in tumors may be inhibited due to mutations of apoptotic elements or to tumor microenvironmental conditions arising from vascular insufficiency. Tumors typically contain regions of hypoxia, low glucose and acidosis. Hypoxic cells compromise treatment partly because of reduced fixation of damage during radiotherapy and partly because they promote a more malignant phenotype. There is also evidence that hypoxia may inhibit apoptosis. For some cell types, concurrent hypoxia may modulate radiation-induced apoptosis while, for others, post-irradiation hypoxia may be required. This may reflect the activity of different apoptotic pathways. Pathways involving mitochondrial components as well as regulation of SAPK and Fas have been implicated. In addition, several key stages in apoptosis are sensitive to depletion of cellular energy reserves, which results from hypoxia and low glucose conditions. There is also evidence that low pH in tumors can interfere with radiation-induced apoptosis, partly through cell cycle arrest and other undefined mechanisms. CONCLUSIONS: Hypoxia, low glucose and acidosis influence radiation-induced apoptosis and thus may be detrimental to radiotherapy.