Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases.

PURPOSE: Bone metastases secondary to solid tumors increase the risk of skeletal-related events (SREs), including the occurrence of pathological fracture (PF), radiation to bone (RB), surgery to bone (SB), and spinal cord compression (SCC). The aim of this study was to evaluate the impact of SREs on patients' pain, analgesic use, and pain interference with daily functioning. METHODS: Data were combined from patients with solid tumors and bone metastases who received denosumab or zoledronic acid across three identically designed phase 3 trials (N = 5543). Pain severity (worst pain) and pain interference were assessed using the Brief Pain Inventory at baseline and each monthly visit. Analgesic use was quantified using the Analgesic Quantification Algorithm. RESULTS: The proportion of patients with moderate/severe pain and strong opioid use generally increased in the 6 months preceding an SRE and remained elevated, while they remained relatively consistent over time in patients without an SRE. Regression analysis indicated that all SRE types were significantly associated with an increased risk of progression to moderate/severe pain and strong opioid use. PF, RB, and SCC were associated with significantly greater risk of pain interference overall. Results were similar for pain interference with emotional well-being. All SRE types were associated with significantly greater risk of pain interference with physical function. CONCLUSIONS: SREs are associated with increased pain and analgesic use in patients with bone metastases. Treatments that prevent SREs may decrease pain and the need for opioid analgesics and reduce the impact of pain on daily functioning.

EGFR mutations in patients with non small-cell lung cancer in Bulgaria and treatment with gefitinib.

PURPOSE: To evaluate the EGFR mutations in non small cell lung cancer (NSCLC) patients in Bulgaria, as well as to summarize the outcomes of patients with EGFR mutations, treated with gefitinib as first- or subsequent-line therapy. METHODS: From January 2010 to March 2012 tumor samples from773 NSCLC patients were evaluated for EGFR mutations. RESULTS: Seventy-one mutations were found and 34 patients were treated with gefitinib. Complete remission (CR) was achieved in 2 patients (6.9%), partial remission (PR) in 11 (37.9%), stable disease (SD) in 13 (44.8%), and disease progression (PD) in 3 (10.3%). Higher objective response rate was seen in women and in never-smokers.The mean progression-free survival (PFS) was 11.1 months (95% CI 9.1-13.1), registered in 29 patients (median PFS 10 months ; 95% CI 8.9-11.1).Tolerability to gefitinib was acceptable, with prevalence of skin toxicity, and it did not lead to any significant decline of the patients' quality of life. CONCLUSION: This is the first study in Bulgaria to evaluate EGFR mutations in NSCLC patients,which were encountered in 9.4% of the studied population. The present study confirms the benefits of first- and subsequent-lines of gefitinib for the treatment of this patient group. Our data give grounds for the conclusion that gefitinib is an effective and well-tolerated therapeutic option for patients with locally advanced and metastatic NSCLC harboring EGFR mutations.

Pain and health-related quality of life in patients with advanced solid tumours and bone metastases: integrated results from three randomized, double-blind studies of denosumab and zoledronic acid.

PURPOSE: This analysis evaluated patient-reported outcomes and analgesic use in patients with bone metastases from solid tumours across three comparative studies of denosumab and zoledronic acid. METHODS: Pooled data were analysed from three identically designed double-blind phase III studies comparing subcutaneous denosumab 120 mg with intravenous zoledronic acid 4 mg monthly in patients with bone metastases from breast cancer (n = 2,046), castration-resistant prostate cancer (n = 1,901) or other solid tumours (n = 1,597). Pain severity, pain interference, health-related quality of life and analgesic use were quantified. RESULTS: At baseline, approximately half of patients had no/mild pain (53 % [1,386/2,620] denosumab; 50 % [1,297/2,578] zoledronic acid). Denosumab delayed onset of moderate/severe pain by 1.8 months (median, 6.5 vs 4.7 months; hazard ratio, 0.83; 95 % CI, 0.76-0.92; p < 0.001; 17 % risk reduction) and clinically meaningful increases in overall pain interference by 2.6 months (median, 10.3 vs 7.7 months; hazard ratio, 0.83; 95 % CI, 0.75-0.92; p < 0.001; 17 % risk reduction) compared with zoledronic acid. Strong opioid use and worsening of health-related quality of life were less common with denosumab. CONCLUSIONS: Across three large studies of patients with advanced solid tumours and bone metastases, denosumab prevented progression of pain severity and pain interference more effectively than zoledronic acid.

A phase II, open-label, randomized study to assess the efficacy and safety of AZD6244 (ARRY-142886) versus pemetrexed in patients with non-small cell lung cancer who have failed one or two prior chemotherapeutic regimens.

INTRODUCTION: AZD6244 (ARRY-142886) is a potent, selective MEK inhibitor. This study aimed to evaluate the efficacy and safety of AZD6244 versus pemetrexed as second- or third-line treatment in patients with advanced non-small cell lung cancer (NSCLC). METHODS: In this randomized phase II study, patients received either 100 mg oral AZD6244 free-base suspension twice daily or 500 mg/m(2) intravenous pemetrexed once every 3 weeks after pretreatment with a corticosteroid, folic acid, and vitamin B12. The primary end point of the study was the disease progression event count. RESULTS: Eighty-four patients were randomized. Disease progression events were experienced by 28 (70%) and 26 (59%) patients in the AZD6244 and pemetrexed groups, respectively. Median progression-free survival was not statistically significantly different between the AZD6244 and pemetrexed groups (67 versus 90 days, respectively; hazard ratio 1.08, two-sided 80% confidence interval = 0.75-1.54; p = 0.79). Two patients in the AZD6244 group had a best response to treatment of partial response. In the pemetrexed group, one patient achieved a complete response and one patient a partial response. Dermatitis acneiform, diarrhea, nausea, and vomiting were the most frequently reported adverse events with AZD6244, compared with fatigue, anemia, nausea, anorexia, and dermatitis acneiform with pemetrexed. CONCLUSIONS: Oral AZD6244 showed clinical activity as second- or third-line therapy for patients with advanced NSCLC. In an unselected NSCLC population, there is no suggestion that AZD6244 monotherapy offers any advantage over standard treatment with pemetrexed. Based on preclinical data and recent clinical observations, further development of AZD6244 in NSCLC should focus on BRAF or RAS mutation-positive patients and/or AZD6244-based combination regimens.

Patient attitudes towards chemotherapy and survival: a prospective observational study in advanced non-small cell lung cancer.

This multicenter, non-interventional, prospective, observational study aimed to determine whether patients' attitude to chemotherapy is an independent prognostic factor for survival in patients with advanced non-small cell lung cancer (NSCLC) who are treated with gemcitabine-platinum. Chemonaive patients (n=1895) with stage IIIB or IV NSCLC not amenable to curative surgery or radiotherapy were treated with a combination of gemcitabine plus cisplatin/carboplatin and followed for a maximum of 18 months. Patients' attitude to treatment was measured on a 5-point scale and responses were used to assign patients to one of the three need categories: A, maximum extension of survival with the acceptance of high toxicity (60.0% of patients); B, maximum extension of survival only if coupled with normal lifestyle (26.1%); C, relief of symptoms (13.8%). Median survival varied significantly among the need categories (A=13.00 months, B=15.70 months, C=15.33 months; log-rank test P=0.0415). Patient attitude to treatment (need categories) was not a significant prognostic factor for survival after adjusting for known prognostic factors (P=0.0503). After adjusting for baseline differences, patients in this study had a significantly lower risk of death than patients in three randomized trials (hazard ratio 0.879; 95% confidence interval: 0.775, 0.998; P=0.0458). In conclusion, in this observational study, patient attitude to chemotherapy was not an independent prognostic factor of survival.

Patient attitudes towards chemotherapy as assessed by patient versus physician: a prospective observational study in advanced non-small cell lung cancer.

BACKGROUND: In the treatment of advanced cancer, a physician's ability to accurately identify a patient's attitude towards treatment is critical. This paper describes the extent of any differences observed between patient attitudes towards chemotherapy for advanced non-small cell lung cancer (NSCLC) as assessed by patients themselves versus their physicians. PATIENTS AND METHODS: Patients with stage IIIB or IV NSCLC who received gemcitabine plus cisplatin or carboplatin were enrolled into this prospective observational study. Patients and their physicians completed questionnaires containing descriptions of seven patient-specific attitudes. A pre-defined algorithm was used to categorize patients into one of the three 'need' categories based on the questionnaire responses: (A) "maximum extension of survival with acceptance of high toxicity", (B) "maximum extension of survival only if coupled with normal life style", and (C) "relief of symptoms". Each patient was categorized based on his own response, as well as his physician's response. RESULTS: A total of 1895 patients were enrolled from 19 countries across 3 continents. Data from 1884 patients were analysed. Based on patient versus physician responses, respectively, the distribution of patients was 60% versus 39% in need category A, 26% versus 33% in B, and 14% versus 29% in C. Patient self-assessed versus physician-assessed need category identification was aligned for 891 patients (47.3%): 541 (29%) in A, 218 (12%) in B, 132 (7%) in C. While there was slight agreement between the identification of 'need' categories by physicians and patients (kappa=0.18, 95% CI: 0.15-0.21), physicians also tended to place patients further down the scale (towards C) than patients placed themselves (P<0.001). CONCLUSIONS: Patients have varying needs from cancer chemotherapy and it may not always be correctly identified by the treating physician. Physicians may underestimate patient's desire for extended survival compared with symptom relief.