Journal of Thoracic Oncology 2018 May 3 [Link]
Burt BM, Richards WG, Lee HS, Bartel S, Dasilva MC, Gill RR, Jaklitsch MT, Johnson BE, Swanson SJ, Bueno R, Sugarbaker DJ
The primary objective of this single-institution Phase I clinical trial was to establish the maximum tolerated dose (MTD) of gemcitabine added to cisplatin delivered as heated intraoperative chemotherapy (HIOC) following resection of malignant pleural mesothelioma (MPM).
Extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) treatment arms were based on investigators’ assessment of patient fitness and potential for macroscopic complete resection. Previously established intracavitary dosing of cisplatin (175-225 mg/m2) with systemic cytoprotection was used in combination with escalating doses of gemcitabine, following a 3+3 design from 100 mg/m2 in 100 mg increments.
From 2007 to 2011, 141 patients were enrolled and 104 completed treatment. Of those completing treatment the median was age 65 (43-85) and 22 (21%) were females. EPP arm (n=59): epithelioid histology 31 (53%), median radiographic tumor volume 236cc (16-4285cc); P/D arm (n=41): epithelioid 29 (71%), tumor volume 79cc (6-1107cc). Operative mortality was 2%. Thirty-five and 22 serious adverse events were encountered among 27 (46%) and 16 (39%) patients on the EPP and P/D arms, respectively. Dose-limiting toxicity (Grade 3 leukopenia) was observed in two patients at 1100 mg/m2 gemcitabine, establishing the MTD at 1000 mg/m2, in combination with 175 mg/m2 cisplatin. Median overall and recurrence-free survival in treated patients was 20.3 and 10.7 months, respectively.
Combination cisplatin and gemcitabine HIOC can be administered safely and feasibly in the context of complete surgical resection of MPM by EPP or P/D.