Chemotherapy is one of the most important treatment modalities for patients with mesothelioma. Due to the late stage at which the disease is normally diagnosed, many patients will not be eligible for surgery so chemotherapy is likely to be the only curative therapy that is available to them. For patients who are eligible for cytoreductive surgery, such as pleurectomy/decortication or extrapleural pneumonectomy, chemotherapy is likely to used as part of a multimodal treatment protocol. Recent advances in the effectiveness of the available chemotherapy agents have definitely led to improved survival times for some patients, but these successes are mitigated by the fact that the disease is still without cure. Because of this disappointing situation, a significant portion of contemporary mesothelioma research is directed at improving the efficacy of available mesothelioma treatments.

Some of these research programs involve the study of alternative chemotherapy regimens. Even as pemetrexed + cisplatin (Alimta Therapy) has been a real advancement in mesothelioma treatment, additional agents and delivery mechanisms are available from the treatment of other cancers and researchers from around the world are engaged with the application of these methods to mesothelioma. Researchers from Japan have recently published an article that describes their use of a custom-developed heated perfusion technique for the treatment of pleural mesothelioma.

This article is an overview of their method and a summary of their findings.

Overview of the Study

The article describes the authors’ use of intrapleural perfusion hyperthermo-chemotherapy (IPHC) for patients with pleural mesothelioma. Perfusion chemotherapy is an alternative to the standard intravenous delivery mechanism, where the chemotherapy drugs are administered to a particular area of the body instead of being injected into the blood stream. In the case of intrapleural perfusion, the chemotherapy is delivered directly to the pleural surfaces. The drugs are heated to enhance the absorption process, as research has shown that it is easier for tumors to absorb a drug when it is heated to a certain temperature.

The authors report that they had previously had good results when using this technique on patients with pleuritis carcinomatosa, so they decided to investigate its use for pleural mesothelioma. They enrolled six patients into their study, three men and three women. Of these 6 patients, five presented with epitheloid mesothelioma and one presented with the biphasic subtype. Five patients were staged as Stage III and one was declared Stage IV. Because of the small size of the study, the authors state that they were not investigating overall treatment efficacy, but were in fact studying the apoptotic effect the therapy had on the patients who were treated with it.

The procedure was accomplished with patients under general anesthesia. The authors used video-assisted thoracic surgery (VATS) to examine the patients and to perform a biopsy. Before the perfusion was begun, they removed tumor cells from a pleural effusion. When the perfusion was completed, tumor cells were immediately removed from the effusion, and then again at 24 hours and 48 hours post-perfusion. This was done so the authors could prepare an Apoptosis Index (A.I.), which would establish what effect, if any, the treatment had on the pleural mesothelioma.

Results

The authors found that the IPHC treatment demonstrated a significant apoptotic effect on each patient’s mesothelioma cells. The Apoptotic Index describes the percentage of cells within the sample that were undergoing apoptosis when analyzed. The AI of the untreated cells was 3.8% ± 2.0%, while the post-perfusion indices were as follows: immediately-following, 22.8% ± 5.1%, at 24 hours following, 63.8% ± 8.2%, and at 48 hours following, 47.8% ± 6.09%. These are clear indications of the treatment’s noteworthy effects.

Even though the authors were not directly studying treatment efficacy, when they looked at median survival time for these patients, they found figures much higher than normal: 30 months MST vs. the standard 8-12 months.

Conclusion

Recent research has shown that one of the factors that makes mesothelioma so difficult to treat is its natural resistance to apoptosis, so the results these authors are reporting are quite exciting indeed. Even if they were not specifically studying treatment efficacy, the extended survival times demonstrated in this study are also quite impressive. A sample size of six is definitely too small to draw any conclusions from, but the authors feel that the successful rests of their study of pleural mesothelioma are worthy of a larger study.

Labels: chemotherapy, mesothelioma