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Patients with a treatment-free interval of less than 3 months after first-line treatment, failing first-line treatment, with poor performance status or major comorbidities, or with low tolerance to first-line chemotherapy should in general not receive second-line chemotherapy because of very low efficacy. Instead focus should be on palliative measures such as short fractionation of radiotherapy. Patients with a treatment-free interval exceeding 3 months have a much greater chance of benefiting from second-line treatment and should be treated if in good performance and without major comorbidities. The treatment should consist of either re-induction (i.e., PE, consider substituting cisplatin with carboplatin) or administration of a truly non-cross-resistant regimen. Single-agent topotecan is another alternative. Brain metastases should be treated with WBI. The decision to add chemotherapy should follow the same consideration as for patients with extracranial recurrence.

The meta-analysis performed by the Prophylactic Cranial Irradiation Overview Collaborative Group has provided clear evidence of the beneficial effects of this treatment in terms of survival and reduction of cerebral metastasis. Delivery of PCI results in a 5.4% improvement in overall survival at 3 years after the commencement of induction chemotherapy. PCI was also shown to yield a 54% proportional reduction in the incidence of cerebral metastases, from 59% to 33%, at 3 years. Subgroup analysis suggests a trend toward reduced incidence of cerebral metastasis with increased radiation dose and earlier introduction of PCI into the treatment regimen. Further studies will address the effect of different radiation doses and fractionation regimens (including twice-daily, hyperfractionated radiotherapy) and the optimal timing of PCI relative to induction chemotherapy. Evaluation of the data on the neuropsychiatric sequelae of PCI suggest that patients have significant abnormalities at baseline and that there is no demonstrable change after PCI. However, there is a suggestion that PCI delivered concomitantly with chemotherapy may be associated with a significant deterioration in cognitive function.

In the past the prognosis of SCLC has been poor and, for most patients, long-term effects of treatment have not been a major concern. Few patients have lived long enough to develop late treatment-related effects. Newer, safer treatments are now allowing people to live longer. In the most recent series, between 10% and 20% of patients with limited-stage SCLC have been cured. The role of prophylactic cranial irradiation after chemotherapy has been more clearly defined in recent years and the long-term effects are less serious than previously thought. The most important long-term effects of current treatment include renal damage, neurotoxicities, and pulmonary fibrosis. In the future biologic agents will almost certainly have a larger role to play in the management of SCLC. As these agents are introduced, response rates and survival will improve and the long-term sequelae of therapy will become a more important issue.

Investigators from Europe have always played an active role in the clinical development of new treatment strategies and innovative drugs, and they have made valuable contributions to establishing new treatment standards for patients with NSCLC. The most recent results of the IALT study are particularly noteworthy because they mark a first step toward postoperative, adjuvant chemotherapy of NSCLC. Clinical research in Europe prepared well for its tasks over the three decades since 1975, giving rise to a large number of national and supranational high-quality, high-performance cooperative groups. As a result of their close connections with national tumor centers, and especially their clinical and diagnostic units, these groups clearly meet the increasing requirements of current and future clinical research. A good example is the growing cooperation between the EORTC, the primary European organization for clinical cancer research, and highly renowned North American study groups as well as national tumor centers. And there is no doubt that the political changes of the last 15 years have expanded Europe’s capability to perform high-quality clinical trials even further, irrespective of the differences in framework conditions for research that are still evident between the European regions. Rather, border-crossing clinical research in Europe could be seriously threatened by the ever-increasing legal and bureaucratic requirements while research budgets are being reduced.

Unequivocally the history of mesothelioma parallels that of asbestos exposure. The estimation that the asbestos cancer epidemic will cause 10 million deaths past and present renders the need to reach urgently a global ban on asbestos an issue of highest priority, so that the asbestos cancer epidemic will not become more devastating and will not continue indefinitely.