J.S. Myerson

Treatment options for small cell lung cancer - do we have more choice?

Small cell lung cancer (SCLC) is a significant health problem worldwide because of its high propensity for relapse. This review discusses existing and future therapies for the treatment of SCLC.

A phase II study of 18F-fluorodeoxyglucose PET–CT in non-small cell lung cancer patients receiving erlotinib (Tarceva®); objective and symptomatic responses at 6 and 12 weeks

BACKGROUND The aim of this study was to assess if (18)F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)-CT scanning could minimise the time non-responding patients were exposed to erlotinib (Tarceva). METHODS Patients were selected for clinical factors that would predict response to erlotinib. A FDG PET-CT and diagnostic contrast-enhanced (traditional) CT scan were carried out at baseline, and then a FDG PET-CT at 6 weeks and a traditional CT at 12 weeks were repeated. The primary end-point was rate of early progression in patients after 6 weeks, of which a minimum 12 out of 35 were required to make the study worthwhile. The responses at 6 (PET-CT) and 12 weeks (traditional CT) were compared and correlated with symptomatic response at both these time points. RESULTS Forty seven patients were recruited with 38 and 33 patients assessable by FDG PET-CT at 6 weeks and traditional CT at 12weeks, respectively. There was good correlation between Partial response (PR) at both time points and all 10 patients who had a PR at 12 weeks had a PR at 6 weeks. Of the 13 patients with progressive disease (PD) at 12 weeks, seven had PD at 6 weeks and could have had their treatment stopped early. No evaluable patient with stable disease (SD) (8/38) or PD (9/38) on FDG PET-CT at 6 weeks went on to have a later response. Symptomatic response at 6 or 12 weeks did not correlate well with objective response on scanning at either time point. CONCLUSIONS The primary end-point of this study was met as >12 (15/38) patients could have stopped treatment early on the basis of the FDG PET-CT scan result. A FDG PET-CT evaluable response of SD or PD at 6 weeks does predict future lack of response. No correlation was found between response and symptomatic response at either 6 or 12 weeks.

Modest Reductions in Dose Intensity and Drug-Induced Neutropenia have No Major Impact on Survival of Patients with Non-small Cell Lung Cancer Treated with Platinum-Doublet Chemotherapy

Background: Previous studies investigating the effect of increased dose intensity and chemotherapy-induced neutropenia in patients with advanced non-small cell lung cancer (NSCLC) have not consistently shown significant survival benefits. Methods: This retrospective analysis reviewed the outcome of patients receiving palliative chemotherapy for advanced NSCLC (stages III–IV) at the Royal Marsden Hospital. Regimens included cisplatin or carboplatin with either vinorelbine or gemcitabine on days 1 and 8, every 21 days. Patients who received at least four cycles of chemotherapy were classified into groups based on dose intensity, dose reductions, and worst grade of neutropenia for a landmark analysis. Comparisons between these groups for time to progression and overall survival were made by standard univariate and multivariate methods. Results: One hundred sixty-nine of a total of 190 patients who received more than four cycles of chemotherapy during the period between November 1998 and December 2008 were included. One hundred twenty-five (73.9%) patients received four chemotherapy cycles with the remaining receiving up to six cycles. The median relative dose intensity for platinum was 93.9% (62.1–102%) and for vinorelbine/gemcitabine was 91.7% (37.8–105%). Dose reductions were recorded in 64 patients (37.8%), and 65 patients (38.5%) had grades 3 to 4 neutropenia. There were no statistically significant differences in time to progression and overall survival between any of the subgroups. Conclusions: This retrospective analysis demonstrates no significant relationship between survival and dose intensity (<90%), modest dose reductions (<20%), or chemotherapy-induced neutropenia in patients receiving standard doublet platinum containing chemotherapy in NSCLC.

Histology classification is not a predictor of clinical outcomes in advanced non-small cell lung cancer (NSCLC) treated with vinorelbine or gemcitabine combinations

BACKGROUND Until recently, histology has not been clearly or consistently described in the literature as a prognostic or predictive variable in advanced NSCLC studies. We have categorised patients treated with vinorelbine and gemcitabine based first line chemotherapy regimes for advanced NSCLC as either squamous or non-squamous, and also as either adenocarcinoma and non-adenocarcinoma, and compared outcome. MATERIAL AND METHODS 420 patients treated with platinum/gemcitabine, platinum/vinorelbine or single agent gemcitabine or vinorelbine as first line chemotherapy for advanced NSCLC were identified. The influence of pathology on progression free survival (PFS) and overall survival (OS) has been investigated by means of a Cox regression analysis. Hazard ratios with 95% CIs have been given for each pathological type after adjusting for the effects of age, gender, stage (III vs. IV), PS (0/1 vs. 2/3) and treatment type (platinum doublet vs. single agent). RESULTS Neither univariate nor multivariate analysis suggested that there was a significant difference in the response rates for adenocarcinoma vs. non-adenocarcinoma or between squamous and non-squamous pathology. There was no difference in PFS between adenocarcinoma and non-adenocarcinoma pathologies until 8 months (p = 0.98), and there was a statistically significant advantage in PFS for squamous vs. non-squamous pathologies (p = 0.04). Using multivariate Cox regression analysis to adjust for the effects of age, gender, stage, PS, and treatment type, the pathology subtype was not significant. There was no difference in OS in any group. CONCLUSIONS These results suggest that histology may not be considered as a predictor of clinical outcome using these drugs.

Supersensitive Mutation: Two Case Reports of Non-Small-Cell Lung Cancer Treated With Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are indicated in second-line treatment for non-small-cell lung cancer and are, in general, well tolerated. In some patients, side effects can be problematic, necessitating dose attenuation and changes in frequency of administration. A lung tumor with an EGFR mutation confers a high treatment response rate to EGFR TKIs. We present the case reports of 2 patients, both with EGFR mutations in which excellent responses were seen despite dosages and administration frequencies far below recommended levels. In addition, in the face of apparent resistance, small increases in doses overcame this. The possible factors involved in response and resistance to EGFR TKIs and issues around length of treatment are discussed.

Malignant mesothelioma with unexpected contralateral mediastinal shift: a case report

IntroductionContralateral mediastinal shift due to pleural mesothelioma tissue, rather than a pleural effusion, is an unusual clinical feature of mesothelioma.Case presentationA 63-year-old woman with a past history of treated invasive ductal carcinoma of the breast presented with breathlessness and chest pain. Her chest radiograph revealed contralateral mediastinal shift and drainage of over 3 litres of pleural fluid relieved her symptoms. She underwent further investigations which revealed pleural mesothelioma, rather than the expected metastatic breast cancer. When she represented with breathlessness a few months later, a chest radiograph again demonstrated contralateral mediastinal shift. A thoracic ultrasound on this occasion revealed only a small loculated pleural effusion and, unexpectedly, a large volume of malignant tissue, thereby explaining the chest radiograph appearances.ConclusionThis case illustrates mediastinal shift away from the affected side which was caused by mesothelioma tissue itself, rather than by a pleural effusion which is the more usual cause of contralateral mediastinal shift in mesothelioma.

Good Vibrations and the Power of Positron Thinking: Positron Emission Tomography and Endoscopic Ultrasound in Staging of Mesothelioma—Two Case Reports

Case 1 A 55-year-old electrician, smoker, presented with breathlessness and dysphagia. He was found to have a pleural effusion on chest radiograph, and underwent video-assisted thoracoscopic surgery. This revealed pleural deposits, which were biopsied and showed malignant mesothelioma of epithelioid subtype. He had a talc pleurodesis performed. In view of the dysphagia, he had an esophagastroscopy, with no obvious abnormality found. Because of consideration for extrapleural pneumonectomy surgery, in the context of the national MARS trial,1 a positron emission tomography (PET)/computed tomography scan was performed, which demonstrated intense uptake in the left pleura, and less intense uptake in the posterior mediastinum in the region of the esophagus (Figure 1). He then underwent a mediastinoscopy, which found malignant mesothelioma in a mediastinal lymph node, and nondiagnostic tissue from the subcarinal mass. His dysphagia continued, and the subcarinal mass dramatically increased in size (Figure 2). He therefore underwent a further endoscopy with endoscopic ultrasound. A stenosis of the esophagus was seen at 30 cm with edematous mucosa, and under endoscopic ultrasound a circumferential mass between 28 and 40 cm was observed, with a maximal thickness of 23 mm. Biopsies of the esophageal wall confirmed malignant mesothelioma. Over the next few weeks, the dysphagia increased, leading to esophageal stent insertion (Figure 3) with symptomatic improvement.