An international, open-label, randomised trial comparing a two-step approach versus the standard three-step approach of the WHO analgesic ladder in patients with cancer.

BACKGROUND: Worldwide, cancer pain management follows the World Health Organization (WHO) three-step analgesic ladder. Using weak opioids (e.g. codeine) at step 2 is debatable with low-dose strong opioids being potentially better, particularly in low- and middle-income countries where weak opioids are expensive. We wanted to assess the efficiency, safety and cost of omitting step 2 of the WHO ladder. PATIENTS AND METHODS: We carried out an international, open-label, randomised (1 : 1) parallel group trial. Eligible patients had cancer, pain ≥4/10 on a 0-10 numerical rating scale, required at least step 1 (paracetamol) of the WHO ladder and were randomised to the control arm (weak opioid, step 2 of the WHO ladder) or the experimental arm (strong opioid, step 3). Primary outcome was time to stable pain control (3 consecutive days with pain ≤3). Secondary outcomes included distress, opioid-related side-effects and costs. The primary outcome analysis was by intention to treat and the follow-up was for 20 days. RESULTS: One hundred and fifty-three patients were randomised (76 control, 77 experimental). There was no statistically significant difference in time to stable pain control between the arms, P = 0.667 (log-rank test). The adjusted hazard ratio for the control arm was 1.03 (95% confidence interval 0.72-1.49). In the control arm, 38 patients (53%) needed to change to a strong opioid due to ineffective analgesia. The median time to change was day 6 (interquartile range 4-11). Compared to the control arm, patients in the experimental arm had less nausea (P = 0.009) and costs were less. CONCLUSION: This trial provides some evidence that the two-step approach is an alternative option for cancer pain management.

Predicting Response to Radiotherapy in Cancer-Induced Bone Pain: Cytokines as a Potential Biomarker?

AIMS: Radiotherapy (XRT) for cancer-induced bone pain (CIBP) has varying levels of efficacy. A biomarker that predicts likely efficacy could stratify XRT to those most likely to benefit. No biomarker is used in clinical practice, but potential candidate cytokines have been identified. The aim of the present study was to examine the relationship between candidate cytokines and analgesic response after XRT. MATERIALS AND METHODS: An exploratory analysis was undertaken on biobank data from patients who had received single fraction (8 Gy) XRT for CIBP. The biobank data were prospectively collected from multiple centres in the UK as part of a larger clinical trial, which had institutional review board approval and all patients provided written informed consent for the use of their data in future research. Phenotypic data, pain assessments as well as plasma samples were collected at baseline (within the 24 h before the XRT) and at follow-up (4 weeks after XRT). Baseline and follow-up samples were analysed and levels of 16 pre-identified cytokines were compared in patients classified as XRT 'responders' or 'non-responders'. RESULTS: Data from 60 patients were analysed. Insulin-like growth factor binding protein 9 (NOV/CCN3/IGFBP-9) and interleukin-1ß (IL-1ß) were identified as potential predictors of response to XRT. A significant relationship was shown between the response to XRT and the ratio of the median level of NOV/CCN3/IGFBP-9 at baseline:follow-up (P = 0.024). Furthermore, for the patients up to 64 years of age, the median level of NOV/CCN3/IGFBP-9 was significantly different between responders and non-responders (P = 0.047). For IL-1ß, the median level was significantly different between responders and non-responders in patients with breast cancer (P = 0.006). CONCLUSION: Although the present findings do not identify robust biomarkers, this is the first such study to examine the role of cytokines in predicting response to XRT in patients with CIBP, and studies that build on these findings are encouraged.

Mechanisms of cancer-induced bone pain.

Cancer-induced bone pain (CIBP) is common and challenging to treat. Common therapies, such as opioids, radiotherapy and bisphosphonates, are often only partially effective. CIBP is a different entity to inflammatory or neuropathic pain and needs to be considered as such. This overview examines the mechanisms of CIBP; the imbalance of bone turnover, peripheral and central nervous involvement and key neurochemical mediators. The current understanding of the underlying pathophysiology of CIBP is discussed.

Palliative care in the elderly breast cancer patient.

Breast cancer is most common in the elderly and their needs are distinctly different from their younger counterparts. Although tumoricidal treatment may be given, a palliative approach to disease management will probably occur. Palliative and supportive care is an integral component of the management of the elderly breast cancer patient. Common problems include pain, cognitive impairment, depression, lymphoedema and ulcerating disease. End of life care and dignity therapy are also of great importance. Elderly patients with breast cancer are a unique cohort whose nuances with regard to palliative care issues rightly deserve special consideration. The main issues affecting the elderly breast cancer patient are discussed within this overview.

Hammers and nails: a report.

A case report where parathyroid bone disease simulates bone metastases. Subsequent treatment of underlying hyperparathyroidism causes a marked improvement in bone disease, leading to a review of the initial diagnosis.