Highlights • Compared advanced NSCLC phase III trials: pemetrexed–cisplatin with or without pem maintenance. • 4 cycles pem–cis followed by pem maintenance improves survival over 6 cycles pem–cis. • ...Longer exposure to pem–cis or maintenance pem increases some toxicities, but overall incidence low.
Despite the progress in outcomes seen with immunotherapy in various malignancies, including nonsmall cell lung cancer, the benefits are less in small cell lung cancer, malignant pleural mesothelioma ...and thymic epithelial tumours. New effective treatment options are needed, guided
more in-depth insights into the pathophysiology of these rare malignancies. This review comprehensively presents an overview of the clinical presentation, diagnostic tools, staging systems, pathophysiology and treatment options for these rare thoracic cancers. In addition, opportunities for further improvement of therapies are discussed.
Bone metastases are common in patients with advanced non-small-cell lung cancer (NSCLC) and can have devastating consequences. Preventing or delaying bone metastases may improve outcomes.
This study ...evaluated whether zoledronic acid (ZOL) delayed disease progression or recurrence in patients with controlled stage IIIA/B NSCLC after first-line therapy. Patients received vitamin D and calcium supplementation and were randomized to i.v. ZOL (every 3–4 weeks) or no treatment (control). The primary end point was progression-free survival (PFS).
No significant intergroup differences were observed in PFS or overall survival (OS). Median PFS was 9.0 months with ZOL versus 11.3 months for control. Fifteen ZOL-treated (6.6%) and 19 control patients (9.0%) developed bone metastases. Estimated 1-year OS was 81.8% for each group. ZOL safety profile was consistent with previous clinical data, but with higher discontinuations versus control. Fifteen ZOL-treated (6.6%) and five control patients (2.3%) had renal adverse events. Two cases of osteonecrosis of the jaw were reported.
ZOL did not significantly affect PFS or OS in stage IIIA/B NSCLC patients with controlled disease, with a trend toward worsening PFS in the longer-term follow-up. Few patients experienced bone metastases, possibly limiting the potential ZOL impact on disease course.
Adrenal incidentalomas, defined as masses discovered incidentally during imaging investigation of non-adrenal disorders, have become a rather common finding in clinical practice. The prevalence is ...not well characterized and varies among studies. The aim of the present study was to perform a prospective evaluation of the prevalence of adrenal incidentalomas among subjects undergoing computerized tomography (CT) scan of the chest in a screening program of lung cancer (Tic TAC study) in Piedmont, a region of Northwestern Italy. This evaluation included 520 subjects (382 males and 138 females, aged between 55-82 yr), referred to our hospital from April to December 2001. Twenty-three patients with adrenal masses were identified: 21 adrenal adenomas, 1 myelolipoma, and 1 metastasis of lung cancer. Therefore, the overall prevalence of adrenal lesions was 4.4%, and that of benign adrenal masses was 4.2%. This prevalence is higher than those found in previous CT scan series reported in the literature, probably because of the use of high-resolution CT scanning technology. Another factor that influenced our results is that subject age is skewed towards the decades characterized by a greater occurrence of adrenal masses. The outcome of this study confirms that we are presently able to identify incidentally discovered adrenal masses more often than in early years and that the prevalence of adrenal incidentalomas on CT images is approaching that of autopsy series. The present study provides a reliable estimate of the prevalence of adrenal incidentaloma with currently used CT scanners. Notwithstanding that our subjects were at increased risk of lung cancer, the rate of adrenal metastases was low. We think that the present results can be generalized even if we may disclose the lack of histological diagnosis.
Introduction: Cholangiocarcinoma (CCA) is an epithelial cell malignancy arising from bile ducts and/or peribiliary glands. Even though it is considered as a rare neoplasm, its incidence is raising, ...particularly in developed countries. Prognosis is generally poor with few patients who present the inclusion criteria for surgery (the mainstay treatment for this tumour). Several genetic alterations potentially driving tumour progression have been described, representing a possible target for new compounds.
Areas covered: A clinical trial search in Clinicaltrials.gov encompassing a literature search in PubMed and ASCO/ESMO Websites was undertaken in March 2016.
Expert opinion: Notwithstanding a large number of drug tested, results are still disappointing. The main reasons could be the low number of patients enrolled in trials, and the lack of a patient selection based on the biological profile of the tumours. Potential active drugs could have been discharged simply because beneficial in a particular subgroup of patients and not in un unselected population. The future direction of the research should consider biomarker evaluation in order to describe the genetic alteration/s that drive tumour progression and aggressiveness and the mechanisms of drug resistance. Finally, it will be of great interest to consider the results of immunotherapy whenever available.
Treatment outcomes for patients with metastatic non-small-cell lung cancer (NSCLC) are poor with chemotherapy. In recent years, novel agents that target specific, aberrant molecular pathways in NSCLC ...have been under evaluation in clinical trials. To date, just two targeted agents have impacted the natural history of the disease—erlotinib and bevacizumab—each of which targets a single molecule in a signalling pathway involved in NSCLC. While modest, the activity of these single-target agents results in improved clinical outcomes, highlighting the potential of agents that target biological pathways in patients with NSCLC. However, as NSCLC is a highly heterogeneous disease, it is likely that agents with multiple targets (e.g. sunitinib, sorafenib, ZD6474, AZD2171 and AMG 706) may have greater activity than those with single-target activity through inhibition of other pathways that may act as salvage or escape mechanisms for malignant cells. New multi-targeted therapeutic agents currently undergoing clinical evaluation have shown promise as single agents, and preclinical studies have indicated that this efficacy may be due at least in part to the inhibition of multiple pathways that may result in a synergistic antitumour effect.
In stage III non-small-cell lung cancer (NSCLC), the role of systemic chemotherapy preceding or following concurrent chemo-radiotherapy (CT-RT) is unclear. We carried out a randomized phase II study ...to study the toxicity involved-field CT-RT with either induction or consolidation cisplatin–docetaxel (Taxotere).
Patients were randomly assigned to receive two cycles of docetaxel (D) 75 mg/m2 on day 1 and cisplatin (C) 40 mg/m2 on days 1 and 2, either preceding (IND arm) or following (CON arm) concurrent CT-RT, where 66 Gy was delivered using involved-fields concurrent with weekly D 20 mg/m2 and C 20 mg/m2. Patients at higher risk for lung toxicity (V20 > 35%) crossed over to IND arm. Seventy patients were needed to exclude grade (G)3–4 esophagitis in >25%.
Of the 70 eligible patients, 26 were treated in IND and 34 CON; five with V20 >35% switched from CON to IND. The differences in G3–4 esophagitis observed (32/2% IND versus 21/3% CON) were not significantly different from the hypothesized 25% rate. Rates of G≥2 pneumonitis were similar, but IND arm had less G3–4 neutropenia. One-year survival was 63.2% 95% confidence interval (CI) 48.4% to 78.0% and 65.5% (95% CI 48.2% to 82.8%) for the IND and CON arms, respectively.
Both study arms merit further testing in patients with limited volume stage III NSCLC.
Postoperative treatments for lung cancer have been evaluated for more than two decades, but in the majority of the studies
no significant and clinically meaningful effect on survival has been shown. ...In 1995, a meta-analysis of eight cisplatin-based
adjuvant chemotherapy trials in 1,394 patients with non–small cell lung cancer showed a 13% reduction in the risk of death
( P = 0.08). The nonstatistically significant benefit reported in the meta-analysis prompted the planning of several randomized
studies of platinum-based chemotherapy. Three studies addressed the issue of adjuvant chemotherapy in all the resected stages
of non–small cell lung cancer (I-IIIA): the Italian/European study Adjuvant Lung Cancer Project Italy, the International Adjuvant
Lung Cancer study, and the British Big Lung Trial. In contrast to the International Adjuvant Lung Cancer, the Adjuvant Lung
Cancer Project Italy and the underpowered British Big Lung Trial failed to prospectively confirm a significant role of adjuvant
chemotherapy in completely resected non–small cell lung cancer. In this article, we will discuss the findings of the Adjuvant
Lung Cancer Project Italy study in the context of the International Adjuvant Lung Cancer and British Big Lung Trial.
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