Trial Information

A Phase I Trial of Extrapleural Pneumonectomy/Pleurectomy Decortication, Intrathoracic/Intraperitoneal Hyperthermic (IOHC) Cisplatin and Gemcitabine With Intravenous Amifostine and Sodium Thiosulfate Cytoprotection for Patients With Resectable Malignant Pleural Mesothelioma

- This is a dose escalation study of gemcitabine with a fixed dose of cisplatin

- Patients will undergo cytoreductive surgery, which entails the removal of the inner and
outer lining of the lung (pleurectomy/decortication) with or without the lung itself
(extrapleural pneumonectomy), including the lining overlying the pericardium and
diaphragm. Resection of the pericardium and diaphragm are occasionally necessary to
remove all visable tumor. This surgery is part of standard care for malignant pleural
mesothelioma.

- After surgery, a one hour lavage with heated cisplatin and or gemcitabine will be
administered to the hemithorax (and abdominal regions if the diaphragm is no longer
present).

- Patients will remain hospitalized until they have recovered from surgery (usually 7-14
days).

- Patients will return to the hospital during the first month after their surgery to be
evaluated by the medical staff.

- Dose escalation: 1) Three patients will be treated at the first dose level of
gemcitabine. Labs will be monitored on a weekly basis, including a CBC, Chem-7, and
LFT's. In the absence of developing dose-limiting toxicity (DLT) among the first 3
patients treated, dosages can be escalated. DLT will be defined as any grade 3 or
higher renal toxicity, thrombocytopenia or other grade 3 toxicity not related to
surgery 2) If none of these 3 patients have any toxicity, we will proceed to the next
level of gemcitabine. 3) If DLT occurs in 1 of 3 patients at a given dose level, then
3 additional patients are added at that dose (for a total of 6 at this level)If no DLT
occurs, we will proceed to the next level of gemcitabine. If DLT occurs in another
patient, this dose is considered the maximum tolerated dose (MTD). 4) At any dose, 3
cases of DLT lead to discontinuation of recruitment at that dose and enrollment of 3
additional patients at a lower dose.