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Pain is a highly distressing symptom for patients with advanced cancer. WHO analgesic ladder is widely accepted as a guideline for its treatment. Our aim was to describe pain prevalence among patients diagnosed with advanced non-small-cell lung cancer (NSCLC), impact of pain on quality of life (QoL) and adequacy of pain management. Data of 1021 Italian patients enrolled in three randomised trials of chemotherapy for NSCLC were pooled. QoL was assessed by EORTC QLQ-C30 and LC-13. Analgesic consumption during the 3 weeks following QoL assessment was recorded. Adequacy of pain management was evaluated by the Pain Management Index (PMI). Some pain was reported by 74% of patients (42% mild, 24% moderate and 7% severe); 50% stated pain was affecting daily activities (30% a little, 16% quite a bit, 336 very much). Bone metastases strongly affected presence of pain. Mean global QoL linearly decreased from 64.9 to 36.4 from patients without pain to those with severe pain (P < 0.001). According to PMI, 616 out of 752 patients reporting pain (82%) received inadequate analgesic treatment. Bone metastases were associated with improved adequacy and worst pain with reduced adequacy at multivariate analysis. In conclusion, pain is common in patients with advanced NSCLC, significantly affects QoL, and is frequently undertreated. We recommend that: (i) pain self-assessment should be part of oncological clinical practice; (ii) pain control should be a primary goal in clinical practice and in clinical trials; (iii) physicians should receive more training in pain management; (iv) analgesic treatment deserves greater attention in protocols of anticancer treatment. © 2004 Cancer Research UK.

First-line bevacizumab-based therapy has been shown to improve outcomes in patients with advanced non-squamous non-small-cell lung cancer (NSCLC). The recent international phase IV SAiL study (a Study of Avastin [bevacizumab] in combination with platinum-containing chemotherapy in patients with advanced or recurrent non-squamous cell Lung cancer) evaluated the safety and efficacy of bevacizumab combined with standard chemotherapy regimens in routine clinical practice. Here we report the results of a subanalysis of baseline characteristics and efficacy data for Italian patients enrolled in SAiL. In the SAiL study, patients with untreated locally advanced, metastatic or recurrent non-squamous NSCLC received bevacizumab (7.5 or 15 mg/kg) every 3 weeks plus chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. Efficacy was assessed in terms of time to disease progression (TTP) and overall survival (OS). The Italian intent-to-treat population comprised 215 patients from a SAiL population of 2212 patients. At baseline, Italian patients tended to have less advanced disease than the overall population. Thus, the proportion of patients at enrollment with tumour stage IIIb and IV was 23.7 and 76.3 %, respectively, for the Italian population versus 19.7 and 80.3 % for the whole SAiL population. In addition, a higher proportion of Italian patients had an Eastern Cooperative Oncology Group performance status of 0 (72.6 vs. 37.2 %) and the prevalence of co-morbid conditions was lower in Italian patients (59.5 % of Italian patients reported a co-morbid condition and 60.0 % were receiving non-oncological treatment compared with 73.3 and 73.4 %, respectively, of SAiL patients overall). The mean exposures to bevacizumab and to chemotherapy were comparable between the Italian patient group and overall patient population, although cisplatin doublets were more commonly employed in Italian patients whereas carboplatin doublets were more commonly employed in the overall SAiL population. The median TTP and OS times for Italian and SAiL populations were comparable (TTP, 7.8 months vs. 7.8 months; OS, 14.8 months vs. 14.6 months). The results of this subanalysis of the SAiL study of bevacizumab treatment in routine clinical practice suggest that Italian oncologists tend to prescribe bevacizumab to a selected population of patients with less advanced disease than is the case in the overall population. Nevertheless, the first-line use of bevacizumab in combination with chemotherapy offers clinical benefits to Italian patients with advanced or recurrent non-squamous NSCLC.

Background Adenocarcinoma of the lung with EML4-ALK translocation is a rare subtype of Non Small-Cell Lung Cancer (NSCLC) that has recently shown to benefit from treatment with crizotinib. Despite the concerns about the efficacy of crizotinib over cerebral metastases, some reports have described its activity, although always after local treatment with radiotherapy. Recently it has been reported activity of crizotinib over choroidal metastases, again after radiotherapy. Case presentation Herein we report a case of activity of crizotinib over choroidal metastases not previously treated with radiotherapy. Conclusion We suggest crizotinib may be active over choroidal metastases in a patient harboring ALK translocation with no need of radiotherapy.

Background Although first-line therapy for patients affected by advanced mesothelioma is well established, there is a lack of data regarding the impact of second-line treatment. Methods We retrospectively collected data of patients affected by advanced mesothelioma, already treated with first-line therapy based on pemetrexed and platin, with a response (partial response or stable disease) lasting at least 6 months, and re-treated with a pemetrexed-based therapy at progression. The primary objective was to describe time to progression and overall survival after re-treatment. Results Overall across several Italian oncological Institutions we found 30 patients affected by advanced mesothelioma, in progression after a 6-month lasting clinical benefit following a first-line treatment with cisplatin and pemetrexed, and re-challenged with a pemetrexed-based therapy. In these patients we found a disease control rate of 66%, with reduction of pain in 43% of patients. Overall time to progression and survival were promising for a second-line setting of patients with advanced mesothelioma, being 5.1 and 13.6 months, respectively. Conclusions In our opinion, when a patient has a long-lasting benefit from previous treatment with pemetrexed combined with a platin compound, the same treatment should be offered at progression.

Sir, We have read with great interest the article of Kunitoh et al, 2009 published recently on this Journal, about the use of intrapericardial Bleomycin in malignant pericardial effusion (MPE) with lung cancer. We appreciate the effort of trying a prospective, randomised study in this field, but we do not agree with the rationale and the method of the study. First of all, the title is misleading, as the Authors also include cytologically negative effusions among the ‘malignant effusions', without any mention about other means to confirm their malignant nature. At least 30% of pericardial effusions in lung cancer patients are not due to metastases, and these cases should be examined separately (Wang et al, 2000; Porte et al, 1999). Actually, when the Authors did so in the subgroup analysis, the difference between the two groups of treatment is evident (even without a statistically significant difference). A title as: ‘Pericardial effusion in lung cancer patients' should be more appropriate. Second, in the introduction, the Authors assume that the therapy of malignant pericardial effusion is, by definition, pericardial sclerosis, and include the use of various chemotherapeutic agents such as ‘sclerosing'. Actually, Bleomycin has both antineoplastic and sclerosing (with a mechanism analogue to the tetracyclines) properties, whereas platinum, thiotepa and vinblastine are actually ‘pure' antineoplastic drugs. In fact, the goal of the use of these agents is not to simply prevent mechanically the accumulation of the pericardial fluid, but try to cure the pericardial metastases. And this leads to the third, and more important point. Malignant pericardial effusion is a metastatic localisation, and, in our opinion, the goal of treatment should be to try to cure it with antineoplastic agents rather than simply prevent their secondary effects. Echocardiographic evaluation in many lung cancer patients detects discrete pericardial implantations or infiltrations, and in certain patients, diffuses neoplastic deposits. Thus, local chemotherapy has the rationale to control not only the pericardial fluid re-accumulation but the neoplastic process as well. The injection of a chemotherapeutic agent in a limited space, such as the pericardium, with heart's movement allowing the diffusion of the agent to the whole surface, and the slow re-absorption through the lymphatic vessels (the main diffusion way of metastases to the pericardium in lung and other cancers), has several advantages: high intrapericardial concentration of chemotherapy (CT) for several days, low blood concentration (and few systemic side effects) and beneficial effects on the lymphatic system obstruction (Figoli et al, 1987; Reynen et al, 2004; Tomkowski et al, 2004). On the contrary, the exaggerated sclerosing process after intrapericardial instillation is the main problem of sclerosing agents, such as bleomycin. The risk of sclerosing therapy is in fact not only the evolution to constrictive pericarditis (as already reminded by the Authors), but also to effusive-constrictive pericarditis (where even small amount of fluid leads to tamponade because of the reduced compliance of the thickened pericardium), with consequently problems in attempting a second drainage in case of haemodynamic impairment if the effusion is loculated. In the report by Kunitoh et al, among 79 patients, two cases of constrictive pericarditis and two deaths of massive bleeding ‘during attempt of re-drainage …possibly due to crack formation in the ventricular wall upon dissection of the adherent pericardium'. We and others have reported the low complication rate and the effectiveness of local chemotherapy (Lestuzzi et al, 2000; Maisch et al, 2002; Martinoni et al, 2004; Tomkowski et al, 2004; Bischiniotis et al, 2005). In our personal experience of 139 cases of MPE due to various neoplasms (88 lung cancer) and treated with local chemotherapy (platinum in most cases, given either as single 50 mg in 50 ml of saline in single bolus or as 10 mg in 20 ml of saline over 3–5 running days), we had no major complications except for: one case of renal failure (treated with fluid and furosemide), one severe chest pain with electrocardiogram abnormalities (but no troponine increase), one atrial fibrillation requiring DC shock for cardioversion and two late constrictive pericarditis after local CT with platinum. A minority of patients complained of pain or nausea. We had no problems in any of the eight patients who underwent a second pericardiocentesis. In addition, in one of our Institutions (Theagenion Cancer Hospital) 15 lung cancer patients underwent serial cytological examination of the pericardial fluid that showed a remarkable neoplastic burden reduction after the third dose of cisplatin. This acute response of local chemotherapy may predict its long-term favourable effects. About the outcome, our experience is encouraging. In all tumours, the mean effusion-free period of the patients treated with local chemotherapy was 372 days, median 223; at 1, 2, 6 and 12 months, 58, 52, 33 and 16%, respectively, were completely effusion-free. In the subgroup of lung cancer MPE, the mean effusion-free period was 271 days (median 215) and the percentage of completely effusion-free at 1, 2, 6 and 12 months was 65, 57, 35 and 18%, respectively; also including the patients who had persistent mild effusion (without haemodynamic impairment). The success rate in this subgroup raises to 86, 70, 40 and 19%, respectively. Our results are then slightly better, on the long-term period, when compared with those of Kunitoh (who reports an effusion-free survival of 65, 46, 24 and 10% at 1,2,6 and 12 months, respectively), with fewer complications. In conclusion, we feel that sclerosing therapy (with any agent) should not be considered as the first choice treatment for MPE anymore. The use of local CT agent is safer, more rationale and more effective. Coping with lung cancer, platinum is the first-choice drug for systemic therapy (and, logically, for local therapy as well) (D'Addario and Felip, 2008).