Clemens B Tempfer1, Urs Giger-Pabst2, Veronika Seebacher3, Miriam Petersen4, Askin Dogan5, Günther A Rezniczek6. 1. Department of Obstetrics and Gynecology, Marien Hospital Herne, Ruhr-Universität Bochum, Bochum, Germany. Electronic address: clemens.tempfer@rub.de. 2. Department of Surgery, Marien Hospital Herne, Ruhr-Universität Bochum, Bochum, Germany. Electronic address: urs.pabst@elisabethgruppe.de. 3. Department of Gynecology and Gynecologic Oncology, Medical University of Vienna, Vienna, Austria. Electronic address: veronika.seebacher@meduniwien.ac.at. 4. Labor MVZ Eberhard und Partner, Dortmund, Germany. Electronic address: petersen@labmed.de. 5. Department of Obstetrics and Gynecology, Marien Hospital Herne, Ruhr-Universität Bochum, Bochum, Germany. Electronic address: askin.dogan@elisabethgruppe.de. 6. Department of Obstetrics and Gynecology, Marien Hospital Herne, Ruhr-Universität Bochum, Bochum, Germany. Electronic address: guenther.rezniczek@rub.de.
Abstract
OBJECTIVE: We performed a phase I, single-arm, non-randomized, open-label, dose-escalation trial to determine the dose-limiting toxicity of intraperitoneal cisplatin and doxorubicin applied as pressurized intraperitoneal aerosol chemotherapy (PIPAC) in women with recurrent ovarian cancer. METHODS: We used a standard 3 + 3 dose-escalation design with doxorubicin 1.5 mg/m2, cisplatin 7.5 mg/m2 q 4 to 6 weeks for 3 cycles and subsequent dose escalation steps (20% increment per step) in patients with recurrent ovarian cancer and peritoneal carcinomatosis. Toxicity and clinical efficacy were monitored. The primary endpoint was the maximum-tolerable dose. Secondary endpoints included histologic tumor regression and serum parameters. RESULTS: 15 evaluable patients (3, 7, and 5 in cohorts 1, 2, and 3, respectively) on average received 2.3 PIPAC cycles. No dose limiting toxicities were found. Adverse side effects were 1 grade 3 event (colon perforation) and 85 grade 1/2 events including fatigue (n = 19), abdominal pain (n = 18), nausea/vomiting (n = 14), sleep disorder (n = 8), diarrhea (n = 5), and fever (n = 2). Liver and renal toxicity was not observed in any of the 3 cohorts (AST 19.1 ± 3.2, 25.8 ± 6.5, and 22.1 ± 4.5 IU/L, respectively; ALT 14.7 ± 3.5, 18.5 ± 5.6, and 23.3 ± 13.0 IU/L, respectively; GGT 45.7 ± 35.1, 25.2 ± 10.3, and 43.9 ± 26.4 IU/L, respectively; serum creatinine 1.06 ± 0.23, 0.80 ± 0.17, and 0.89 ± 0.35 mg/dL, respectively). No systemic hematologic toxicity, alopecia, or neurotoxicity was noted. The maximum tolerable dose was not reached. Histologic tumor regression was observed in 7/11 (64%) patients who underwent ≥2 PIPAC cycles. CONCLUSIONS: PIPAC with cisplatin and doxorubicin may be safely used at an intraperitoneal dose of 10.5 mg/m2 and 2.1 mg/m2, respectively. Systemic toxicity of this therapy is low.
OBJECTIVE: We performed a phase I, single-arm, non-randomized, open-label, dose-escalation trial to determine the dose-limiting toxicity of intraperitoneal cisplatin and doxorubicin applied as pressurized intraperitoneal aerosol chemotherapy (PIPAC) in women with recurrent ovarian cancer. METHODS: We used a standard 3 + 3 dose-escalation design with doxorubicin 1.5 mg/m2, cisplatin 7.5 mg/m2 q 4 to 6 weeks for 3 cycles and subsequent dose escalation steps (20% increment per step) in patients with recurrent ovarian cancer and peritoneal carcinomatosis. Toxicity and clinical efficacy were monitored. The primary endpoint was the maximum-tolerable dose. Secondary endpoints included histologic tumor regression and serum parameters. RESULTS: 15 evaluable patients (3, 7, and 5 in cohorts 1, 2, and 3, respectively) on average received 2.3 PIPAC cycles. No dose limiting toxicities were found. Adverse side effects were 1 grade 3 event (colon perforation) and 85 grade 1/2 events including fatigue (n = 19), abdominal pain (n = 18), nausea/vomiting (n = 14), sleep disorder (n = 8), diarrhea (n = 5), and fever (n = 2). Liver and renal toxicity was not observed in any of the 3 cohorts (AST 19.1 ± 3.2, 25.8 ± 6.5, and 22.1 ± 4.5 IU/L, respectively; ALT 14.7 ± 3.5, 18.5 ± 5.6, and 23.3 ± 13.0 IU/L, respectively; GGT 45.7 ± 35.1, 25.2 ± 10.3, and 43.9 ± 26.4 IU/L, respectively; serum creatinine 1.06 ± 0.23, 0.80 ± 0.17, and 0.89 ± 0.35 mg/dL, respectively). No systemic hematologic toxicity, alopecia, or neurotoxicity was noted. The maximum tolerable dose was not reached. Histologic tumor regression was observed in 7/11 (64%) patients who underwent ≥2 PIPAC cycles. CONCLUSIONS:PIPAC with cisplatin and doxorubicin may be safely used at an intraperitoneal dose of 10.5 mg/m2 and 2.1 mg/m2, respectively. Systemic toxicity of this therapy is low.
Authors: Mustafa Raoof; Gautam Malhotra; Adrian Kohut; Michael O'Leary; Paul Frankel; Thuy Tran; Marwan Fakih; Joseph Chao; Dean Lim; Yanghee Woo; Isaac B Paz; Michael Lew; Mihaela C Cristea; Lorna Rodriguez-Rodriguez; Yuman Fong; Andrew Blakely; Richard Whelan; Marc A Reymond; Amit Merchea; Thanh H Dellinger Journal: Ann Surg Oncol Date: 2021-08-13 Impact factor: 5.344