Asbestos Exposure - Mesothelioma, Immunotherapy
Future Prospects
In the past there has been a tendency to think of diffuse malignant pleural mesothelioma as one disease in therapeutic terms, irrespective of histological type and tumor stage. This does not happen with other tumors and is equally illogical and inappropriate in mesothelioma. As with other tumors, early diagnosis while the disease is still in stage I or even at an "in situ" stage must be the goal in order to maximize therapeutic options, particularly if immunotherapy or gene therapy is to be used.
Patients with pure epithelial mesothelioma have a better prognosis and respond better to trimodality therapy. Stage I patients with epithelial mesothelioma who meet the fitness criteria described above should therefore be offered the option of radical surgery in combination with chemotherapy and radiotherapy. Further research is required to determine the optimum combination of these modalities in terms of timing of adjuvant therapy, individual drugs, use of hyperthermia and route of administration. The place of immunotherapy and gene therapy as adjunctive treatments also remains to be defined. For example, it may be possible to reduce tumor bulk and perhaps downstage the disease with immunotherapy prior to radical surgery, if treatment is started early enough. Gene therapy may have a role either preoperatively or in destroying the microscopic disease that remains after radical surgery. These and other combinations of treatment need to be tested in well-designed clinical trials, probably on a multicenter basis in order to enroll sufficient numbers of patients.
Finding means to improve treatment for sarcomatous and mixed histology mesothelioma remains an even greater challenge. At present radical surgery does not seem worthwhile for these patients when combined with currently employed chemotherapy and radiotherapy. However, chemotherapy combinations used for treating other sarcomas need to be evaluated as adjunctive therapy before radical surgery is abandoned altogether as a treatment modality.
Much remains to be learned about tumor biology and immunology and specifically why some tumors of apparently identical histology respond better to therapy than others. Ultimately the hope must be that development of tumor markers capable of identifying very early asymptomatic malignant change in patients at risk, coupled with the discovery of the fundamental cause of malignant transformation in mesothelial cells at the genetic level, will lead to gene therapy given early enough to restore "normality" to these cells. Diffuse malignant mesothelioma of the pleura should not be labeled as "incurable" until all possible treatment combinations have been properly evaluated in well-designed clinical trials. A collaborative approach involving basic scientists and oncologists, thoracic surgeons and physicians with experience in treating mesothelioma is essential. Because mesothelioma is still a relatively rare tumor despite its increasing frequency, treatment should ideally be concentrated in relatively few supraregional centers in order to maximize expertise, and allow innovative treatment combinations to be implemented with the greatest chance of success. Evaluation of new therapeutic approaches will be achieved more rapidly if these supraregional centers collaborate in multicenter trials. The nihilistic approach of simply waiting until the mesothelioma epidemic eventually begins to decline spontaneously in 20 or 30 years is untenable, in view of the hundreds of thousands of deaths which will result if no effective treatment is found [3].
New Chemotherapy Drugs
There are a number of new chemotherapy drugs garnering a great deal of attention. Alimta, Veglin and Onconase were developed for the treatment of malignant mesothelioma and other types of cancer such as lymphoma and renal cell carcinoma.