Breakthrough cancer pain: review and calls to action to improve its management.

In this paper, we review the current state of breakthrough cancer pain (BTcP) management. BTcP is a heterogeneous condition and a global problem for cancer patients. It is often managed suboptimally, which results in a negative outcome for patients, healthcare providers, and healthcare systems. Several barriers to the appropriate management of BTcP have been identified. These include, among others, an incomplete definition of BTcP, poor training of healthcare providers and patients alike, a lack of a multidisciplinary approach and the absence of specific protocols and tools. We provide some actions to help physicians and patients improve their approach to BTcP, including specific training, the design of easy-to-use tools for BTcP identification and assessment (such as checklists and pocket-sized cards), individualized treatment, and the use of multidisciplinary teams.

HLA-G as a new tumor biomarker: detection of soluble isoforms of HLA-G in the serum and saliva of patients with colorectal cancer.

INTRODUCTION: Recent medical investigations suggest that HLA-G, due to its tolerogenic properties, can be used as a biomarker in the diagnosis, treatment, and prognosis of different neoplasms. This observational prospective pilot study aims at detecting sHLA-G in the serum and saliva of patients diagnosed with colorectal cancer (CRC). For this purpose, we compared the expression of sHLA-G from patients with a control sample from a healthy population. MATERIALS AND METHODS: Using the specific enzyme-linked immunosorbent assay (ELISA) method, the expression of sHLA-G in the serum and saliva samples from patients affected by CRC (n = 20) and in a control sample (n = 10) were analyzed. RESULTS: The data showed that in patients with CRC, salivary sHLA-G values were significantly higher than in the control group (18.84 U/ml versus 6.3 U/ml, p = 0.036). In addition, higher levels of sHLA-G were observed in the saliva of patients with CRC in more advanced stages, compared with patients in early stages (24.2 U/ml vs. 8.1 U/ml, p = 0.019). A significant correlation was observed between the concentration of sHLA-G in the serum and saliva of the analyzed samples (Spearman correlation 0.7, p = 0.004). CONCLUSIONS: This study demonstrates, for the first time, the possibility of detecting sHLA-G in the saliva of patients with CRC, resulting in a less invasive alternative to venipuncture. Likewise, we propose that sHLA-G could be an attractive molecular target based on its significant high levels in advanced stages.

Effectiveness of daily versus non-daily granulocyte colony-stimulating factors in patients with solid tumours undergoing chemotherapy: a multivariate analysis of data from current practice.

We conducted a multicentre, retrospective, observational study including patients with solid tumours (excluding breast cancer) that received granulocyte colony-stimulating factors (G-CSF) and chemotherapy. We investigated the effectiveness of daily vs. non-daily G-CSFs (pegfilgrastim) adjusting by potential confounders. The study included 391 patients (211 daily G-CSF; 180 pegfilgrastim), from whom 47.3% received primary prophylaxis (PP) (57.8% pegfilgrastim), 26.3% secondary prophylaxis (SP: initiation after cycle 1 and no reactive treatment in any cycle) (51.5% pegfilgrastim) and 26.3% reactive treatment (19.4% pegfilgrastim). Only 42.2% of patients with daily G-CSF and 46.2% with pegfilgrastim initiated prophylaxis within 72 h after chemotherapy, and only 10.5% of patients with daily G-CSF received it for ≥ 7 days. In the multivariate models, daily G-CSF was associated with higher risk of grade 3-4 neutropenia (G3-4N) vs. pegfilgrastim [odds ratio (OR): 1.73, 95% confidence interval (CI): 1.004-2.97]. Relative to SP, PP protected against G3-4N (OR for SP vs. PP: 6.0, 95%CI: 3.2-11.4) and febrile neutropenia (OR: 3.1, 95%CI: 1.1-8.8), and was associated to less chemotherapy dose delays and reductions (OR for relative dose intensity <85% for SP vs. PP: 3.1, 95%CI: 1.7-5.4) and higher response rate (OR: 2.1, 95%CI: 1.2-3.7). Data suggest that pegfilgrastim, compared with a daily G-CSF, and PP, compared with SP, could be more effective in preventing neutropenia and its related events in the clinical practice.

Phase II trial assessing the combination of gemcitabine and cisplatin in advanced non-small cell lung cancer (NSCLC).

BACKGROUND: There is need for more active and better tolerated combinations in non-small cell lung cancer (NSCLC). The Spanish Lung Cancer Group (SLCG) therefore conducted this phase II study to define the efficacy and toxicity profile of the combination of higher doses than usual of gemcitabine along with cisplatin in patients with advanced NSCLC. PATIENTS AND METHODS: Forty patients with pathologically documented advanced NSCLC were included in this trial (34 men, six women; aged 34-74 years; mean 64 years). Twenty-two patients had unresectable stage IIIB disease and 18 had stage IV disease. Karnofsky performance status was > or =70%. In five patients, surgery had previously been performed and four patients had received radiotherapy. Gemcitabine at a dose of 1200 mg/m2 was administered weekly (days 1, 8 and 15) and cisplatin 100 mg/m2 on day 15 of each 28-day cycle. RESULTS: Responses were scored according to standard World Health Organization criteria. Of 40 assessable patients, 19 had a partial response for an overall response rate of 47.5% (95% confidence interval (CI) 32-64%). To date, median survival for the whole group is 10.4 months (95% CI 6.2-11.7 months), with a 1-year survival rate of 35%. Toxicity was mainly haematological. Seven patients (18%) had grade 4 neutropenia (one episode of febrile neutropenia). Thrombocytopenia (12.8% grade 3 and 2.6% grade 4) was not associated with clinical bleeding. One patient had a grade 4 transient rise in transaminase. There was no grade 3 or 4 renal toxicity. There was no grade 4 symptomatic toxicity. The most common grade 3 toxicities were nausea and vomiting (28.2%) and alopecia (10.3%) both related to cisplatin. CONCLUSIONS: Gemcitabine can be safely administered at a dose of 1200 mg/m2 in combination with cisplatin. Thrombocytopenia seems to be less than in schedules with cisplatin given on day 1. The results of this studyshow promising activity (47.5% response rate) with modest toxicity. As this combination of gemcitabine and cisplatin deserves further evaluation in prospective randomized trials, the SLCG is comparing gemcitabine-cisplatin with etoposide-cisplatin in a phase III randomized study.

Modified weekly regimen with vinorelbine as a single agent in unresectable non-small cell lung cancer.

After a 26% response rate was reported with a 20/mg/m2/week vinorelbine (VRL) dose, a multicenter phase II trial of a modified weekly VRL treatment protocol (30 mg/m2 days 1 and 8 every 21 days) for unresectable non-small cell lung cancer (NSCLC) was designed to determine its clinical activity, toxicity, and survival of treated patients. As myelotoxicity frequently precludes the administration of VRL, by suppressing the dose that would correspond to day 15 of a weekly protocol, we allowed bone marrow recovery to take place and avoided the administration of the drug at the nadir of the cycle. The trial included 71 consecutive, previously untreated patients with unresectable and measurable disease. A total of 297 three-week treatment courses were administered with an average of 4 courses per patient (range 1-11). Results showed that in spite of attaining a median dose intensity of 19 mg/m2/week, this modified weekly VRL treatment regimen has a low level of activity (7.5% response rate) in NSCLC. Although a more tolerable level of toxicity is achieved, in order to maintain its antitumor activity, the recommended dose of VRL when given alone for NSCLC treatment (30 mg/m2/weekly) should not be decreased.