Mariela Blum Murphy1, Naruhiko Ikoma2, Xuemei Wang3, Jeannelyn Estrella4, Sinchita Roy-Chowdhuri4, Prajnan Das5, Bruce D Minsky5, Shumei Song1, Paul Mansfield2, Jaffer Ajani1, Brian Badgwell6. 1. Departments of Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA. 2. Department of Surgical Oncology, Unit 1484, MD Anderson Cancer Center, Houston, TX, USA. 3. Departments of Biostatistics, MD Anderson Cancer Center, Houston, TX, USA. 4. Departments of Pathology, MD Anderson Cancer Center, Houston, TX, USA. 5. Departments of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA. 6. Department of Surgical Oncology, Unit 1484, MD Anderson Cancer Center, Houston, TX, USA. bbadgwell@mdanderson.org.
Abstract
BACKGROUND: The purpose of this phase I trial is to evaluate the safety and toxicity of laparoscopic hyperthermic intraperitoneal perfusion with chemotherapy (HIPEC), combining mitomycin, cisplatin, and paclitaxel for patients with gastric cancer metastatic to the peritoneum. PATIENTS AND METHODS: A Bayesian optimal interval design was used to prospectively identify the safety and tolerability of escalating doses of paclitaxel in combination with flat doses of mitomycin (30 mg) and cisplatin (200 mg) during laparoscopic HIPEC. The primary objective is to define the maximum tolerated dose. Secondary endpoints include surgical complications and overall survival (OS). RESULTS: A total of 27 patients were treated between 11/2017 and 11/2018. No dose-limiting toxicities were observed. Treatment-related grade 1-2 toxicities were leukopenia (11%), oral dysesthesia (4%), arthralgia (4%), and diarrhea (4%). Treatment-related grade 3-4 toxicities included leukopenia (4%) and neutropenia (4%). The maximum dose for paclitaxel was 60 mg/m2. Rates of Clavien-Dindo surgical complications were grade I 96% (all electrolyte deficiencies requiring replacement), II 4%, III 0%, IV 0%, and V 4%. The median follow-up time was 15 months. One- and 2-year OS rates from date of metastatic disease were 73.9% and 58.1%, respectively. CONCLUSIONS: Laparoscopic HIPEC with mitomycin, cisplatin, and paclitaxel may be safely used at intraperitoneal doses of 30 mg, 200 mg, and 60 mg/m2, respectively. Although electrolyte abnormalities were common, systemic toxicity was low. Survival rates were promising, supporting further research into intraperitoneal therapy for stage IV gastric cancer.
BACKGROUND: The purpose of this phase I trial is to evaluate the safety and toxicity of laparoscopic hyperthermic intraperitoneal perfusion with chemotherapy (HIPEC), combining mitomycin, cisplatin, and paclitaxel for patients with gastric cancer metastatic to the peritoneum. PATIENTS AND METHODS: A Bayesian optimal interval design was used to prospectively identify the safety and tolerability of escalating doses of paclitaxel in combination with flat doses of mitomycin (30 mg) and cisplatin (200 mg) during laparoscopic HIPEC. The primary objective is to define the maximum tolerated dose. Secondary endpoints include surgical complications and overall survival (OS). RESULTS: A total of 27 patients were treated between 11/2017 and 11/2018. No dose-limiting toxicities were observed. Treatment-related grade 1-2 toxicities were leukopenia (11%), oral dysesthesia (4%), arthralgia (4%), and diarrhea (4%). Treatment-related grade 3-4 toxicities included leukopenia (4%) and neutropenia (4%). The maximum dose for paclitaxel was 60 mg/m2. Rates of Clavien-Dindo surgical complications were grade I 96% (all electrolyte deficiencies requiring replacement), II 4%, III 0%, IV 0%, and V 4%. The median follow-up time was 15 months. One- and 2-year OS rates from date of metastatic disease were 73.9% and 58.1%, respectively. CONCLUSIONS: Laparoscopic HIPEC with mitomycin, cisplatin, and paclitaxel may be safely used at intraperitoneal doses of 30 mg, 200 mg, and 60 mg/m2, respectively. Although electrolyte abnormalities were common, systemic toxicity was low. Survival rates were promising, supporting further research into intraperitoneal therapy for stage IV gastric cancer.
Authors: Mahul B Amin; Frederick L Greene; Stephen B Edge; Carolyn C Compton; Jeffrey E Gershenwald; Robert K Brookland; Laura Meyer; Donna M Gress; David R Byrd; David P Winchester Journal: CA Cancer J Clin Date: 2017-01-17 Impact factor: 508.702
Authors: Terence C Chua; Brendan J Moran; Paul H Sugarbaker; Edward A Levine; Olivier Glehen; François N Gilly; Dario Baratti; Marcello Deraco; Dominique Elias; Armando Sardi; Winston Liauw; Tristan D Yan; Pedro Barrios; Alberto Gómez Portilla; Ignace H J T de Hingh; Wim P Ceelen; Joerg O Pelz; Pompiliu Piso; Santiago González-Moreno; Kurt Van Der Speeten; David L Morris Journal: J Clin Oncol Date: 2012-05-21 Impact factor: 44.544
Authors: Naruhiko Ikoma; Hsiang-Chun Chen; Xuemei Wang; Mariela Blum; Jeannelyn S Estrella; Keith Fournier; Paul Mansfield; Jaffer Ajani; Brian D Badgwell Journal: Ann Surg Oncol Date: 2017-03-22 Impact factor: 5.344
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Authors: Naruhiko Ikoma; Mariela Blum; Yi-Ju Chiang; Jeannelyn S Estrella; Sinchita Roy-Chowdhuri; Keith Fournier; Paul Mansfield; Jaffer A Ajani; Brian D Badgwell Journal: Ann Surg Oncol Date: 2016-07-06 Impact factor: 5.344
Authors: Eric Van Cutsem; Vladimir M Moiseyenko; Sergei Tjulandin; Alejandro Majlis; Manuel Constenla; Corrado Boni; Adriano Rodrigues; Miguel Fodor; Yee Chao; Edouard Voznyi; Marie-Laure Risse; Jaffer A Ajani Journal: J Clin Oncol Date: 2006-11-01 Impact factor: 44.544
Authors: Tristan D Yan; Marcello Deraco; Dario Baratti; Shigeki Kusamura; Dominique Elias; Olivier Glehen; François N Gilly; Edward A Levine; Perry Shen; Faheez Mohamed; Brendan J Moran; David L Morris; Terence C Chua; Pompiliu Piso; Paul H Sugarbaker Journal: J Clin Oncol Date: 2009-11-16 Impact factor: 44.544