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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 8/2020

01-08-2020 | Leukopenia | Gastrointestinal Oncology

Phase I Trial of Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) with Cisplatin, Mitomycin, and Paclitaxel in Patients with Gastric Adenocarcinoma and Associated Carcinomatosis or Positive Cytology

Authors: Mariela Blum Murphy, MD, Naruhiko Ikoma, MD, MS, Xuemei Wang, MS, Jeannelyn Estrella, MD, Sinchita Roy-Chowdhuri, MD, PhD, Prajnan Das, MD, Bruce D. Minsky, MD, Shumei Song, PhD, Paul Mansfield, MD, Jaffer Ajani, MD, Brian Badgwell, MD, MS

Published in: Annals of Surgical Oncology | Issue 8/2020

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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.
Literature
1.
Thomassen I, van Gestel YR, van Ramshorst B, et al. Peritoneal carcinomatosis of gastric origin: a population-based study on incidence, survival and risk factors. Int J Cancer. 2014;134(3):622–8.PubMedCrossRef
2.
3.
Amin MB, Greene FL, Edge SB, et al. The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin. 2017;67(2):93–9.PubMedCrossRef
4.
Ikoma N, Blum M, Chiang YJ, et al. Yield of staging laparoscopy and lavage cytology for radiologically occult peritoneal carcinomatosis of gastric cancer. Ann Surg Oncol. 2016;23(13):4332–7.PubMedCrossRef
5.
Ikoma N, Chen HC, Wang X, et al. Patterns of initial recurrence in gastric adenocarcinoma in the era of preoperative therapy. Ann Surg Oncol. 2017;24(9):2679–87.PubMedCrossRef
6.
Yan TD, Deraco M, Baratti D, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience. J Clin Oncol. 2009;27(36):6237–42.PubMedCrossRef
7.
Chua TC, Moran BJ, Sugarbaker PH, et al. Early- and long-term outcome data of patients with pseudomyxoma peritonei from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. J Clin Oncol. 2012;30(20):2449–56.PubMedCrossRef
8.
Badgwell B, Blum M, Das P, et al. Phase II trial of laparoscopic hyperthermic intraperitoneal chemoperfusion for peritoneal carcinomatosis or positive peritoneal cytology in patients with gastric adenocarcinoma. Ann Surg Oncol. 2017;24(11):3338–44.PubMedCrossRef
9.
Van Cutsem E, Moiseyenko VM, Tjulandin S, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 study group. J Clin Oncol. 2006;24(31):4991–7.PubMedCrossRef
10.
Kobayashi D, Kodera Y. Intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis. Gastric Cancer. 2017;20(Suppl 1):111–21.PubMedCrossRef
11.
Yonemura Y, Endou Y, Bando E, et al. Effect of intraperitoneal administration of docetaxel on peritoneal dissemination of gastric cancer. Cancer Lett. 2004;210(2):189–96.PubMedCrossRef
12.
Chan DY, Syn NL, Yap R, et al. Conversion surgery post-intraperitoneal paclitaxel and systemic chemotherapy for gastric cancer carcinomatosis peritonei. Are we ready? J Gastrointest Surg. 2017;21(3):425–33.PubMedCrossRef
13.
Clavien PA, Barkun J, de Oliveira ML, et al. The Clavien–Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250(2):187–96.CrossRef
14.
Ajani JA, D’Amico TA, Almhanna K, et al. Gastric cancer, version 3.2016, NCCN clinical practice guidelines in oncology. JNCCN. 2016;14(10):1286–312.PubMed
15.
16.
17.
Badgwell B, Blum M, Das P, et al. Lessons learned from a phase II clinical trial of laparoscopic HIPEC for gastric cancer. Surg Endosc. 2018;32(1):512.PubMedCrossRef
18.
Kusamura S, Dominique E, Baratti D, Younan R, Deraco M. Drugs, carrier solutions and temperature in hyperthermic intraperitoneal chemotherapy. J Surg Oncol. 2008;98(4):247–52.PubMedCrossRef
19.
Newhook TE, Agnes A, Blum M, et al. Laparoscopic hyperthermic intraperitoneal chemotherapy is safe for patients with peritoneal metastases from gastric cancer and may lead to gastrectomy. Ann Surg Oncol. 2019;26:1394–400.PubMedCrossRef
20.
Kapoor R, Robinson KA, Cata JP, et al. Assessment of nephrotoxicity associated with combined cisplatin and mitomycin C usage in laparoscopic hyperthermic intraperitoneal chemotherapy. Int J Hyperth. 2019;36:1–6.CrossRef
21.
Kapoor R, Robinson KA, Badgwell B. Nephrotoxic synergism of cisplatin and mitomycin-C for hyperthermic intraperitoneal chemotherapy and cytoreductive surgery. Int J Hyperth. 2018;34(5):601.CrossRef
22.
Yang XJ, Huang CQ, Suo T, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial. Ann Surg Oncol. 2011;18(6):1575–81.PubMedPubMedCentralCrossRef
23.
Bonnot PE, Piessen G, Kepenekian V, et al. Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastases (CYTO-CHIP study): a propensity score analysis. J Clin Oncol. 2019;37:2028–40.PubMedCrossRef
24.
Zivanovic O, Abramian A, Kullmann M, et al. HIPEC ROC I: a phase I study of cisplatin administered as hyperthermic intraoperative intraperitoneal chemoperfusion followed by postoperative intravenous platinum-based chemotherapy in patients with platinum-sensitive recurrent epithelial ovarian cancer. Int J Cancer. 2015;136(3):699–708.PubMed
25.
Lemoine L, Sugarbaker P, Van der Speeten K. Drugs, doses, and durations of intraperitoneal chemotherapy: standardising HIPEC and EPIC for colorectal, appendiceal, gastric, ovarian peritoneal surface malignancies and peritoneal mesothelioma. Int J Hyperth. 2017;33(5):582–92.CrossRef
26.
Ansaloni L, Coccolini F, Morosi L, et al. Pharmacokinetics of concomitant cisplatin and paclitaxel administered by hyperthermic intraperitoneal chemotherapy to patients with peritoneal carcinomatosis from epithelial ovarian cancer. Br J Cancer. 2015;112(2):306–12.PubMedCrossRef
Metadata
Title
Phase I Trial of Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) with Cisplatin, Mitomycin, and Paclitaxel in Patients with Gastric Adenocarcinoma and Associated Carcinomatosis or Positive Cytology
Authors
Mariela Blum Murphy, MD
Naruhiko Ikoma, MD, MS
Xuemei Wang, MS
Jeannelyn Estrella, MD
Sinchita Roy-Chowdhuri, MD, PhD
Prajnan Das, MD
Bruce D. Minsky, MD
Shumei Song, PhD
Paul Mansfield, MD
Jaffer Ajani, MD
Brian Badgwell, MD, MS
Publication date
01-08-2020
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 8/2020
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-020-08226-x

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