Abstract
Background
The present study was designed to assess the feasibility and efficiency of intraperitoneal and intravenous neoadjuvant chemotherapy in gastric cancer patients with peritoneal dissemination.
Methods
The study subjects were 25 treatment-naïve patients with gastric cancer. Patients with positive cytology or with peritoneal carcinomatosis received neoadjuvant intraperitoneal and systemic chemotherapy (NIPS), comprising intraperitoneal (i.p.) mitomycin C (MMC) and cisplatin (CDDP), followed by two cycles of intravenous triplet chemotherapy of docetaxel, 5-fluorouracil (5-FU), and CDDP. Gastrectomy with lymph node dissection was performed after NIPS in patients free of peritoneal deposits, confirmed by staging laparoscopy.
Results
Seventeen patients had measurable lymph node metastases by the RECIST criteria. CT examination showed response to the treatment in ten (59%, 0 complete response, 10 partial response). Of the 25 patients, 14 (56%) showed negative results on peritoneal cytology with no macroscopic peritoneal metastasis, whereas the remaining 11 were cancer cell-positive on peritoneal cytology or macroscopic peritoneal metastasis even after NIPS. The median survival time for all 25 patients was 16.7 months. Prognosis was better in patients who showed negative cytology and disappearance of peritoneal cancer metastases after NIPS than in those with positive cytology or existing peritoneal deposits (P < 0.0001). The predominant toxicity was myelosuppression and grade 3–4 leukopenia and neutropenia occurred in 20 (80%) patients, which were manageable. No treatment-related mortality was observed during and after NIPS and surgery.
Conclusions
The results of this prospective phase II study indicated that the newly designed NIPS was highly effective and well tolerated in patients with advanced gastric cancer and peritoneal dissemination.
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References
Dupont JB, Lee JR, Burton GR, et al. Adenocarcinoma of the stomach: review of 1497 cases. Cancer. 1978;41:941–7.
Yamada E, Miyaishi S, Nakazato H, et al. The surgical treatment of cancer of the stomach. Int Surg. 1980;65:387–99.
Bando E, Yonemura Y, Takeshita Y, et al. Intraoperative lavage for cytological examination in 1,297 patients with gastric carcinoma. Am J Surg. 1999;178:256–62.
Benevolo M. Diagnostic and prognostic value of peritoneal immunocytology in gastric cancer. J Clin Oncol. 1998;16:3406–11.
Koga S, Kaibara N, Iitsuka Y, et al. Prognostic significance of intra-peritoneal free cancer cells in gastric cancer patients. J Cancer Res Clin Oncol. 1984;108:236–8.
Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma o the stomach or gastroesophageal junction. N Engl J Med. 2001;345:725–30.
Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ; MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for respectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20.
Ajani JA, Fairweather J, Dumas P, Patt YZ, Pazdur R, Mansfield PF. Phase II study of Taxol in patients with advanced gastric carcinoma. Cancer J Sci Am. 1988;4:269–74.
Einzig AI, Neuberg D, Remick SC, Karp DD, O’Dwyer PJ, Stewart JA, Benson AB 3rd. Phase II trial of docetaxel (Taxotere) in patients with adenocarcinoma of the upper gastrointestinal tract previously untreated with cytotoxic chemotherapy: the Eastern Cooperative Oncology Group (ECOG) results of protocol E1293. Med Oncol. 1996;13:87–93.
Futatsuki K, Wakui A, Nakao I, Sakata Y, Kambe M, Shimada Y, Yoshino M, Taguchi T, Ogawa N. Late phase II study of irinotecan hydrochloride (CPT-11) in advanced gastric cancer. CPT-11 Gastrointestinal Cancer Study Group. Jpn J Cancer Chemother. 1994;21:1033–8.
Taguchi T, Tsukagoshi S, Furue H, Niitani H, Noda K. Phase I clinical study of oxaliplatin. Jpn J Cancer Chemother. 1998;25:1899–907.
Sakata Y, Ohtsu A, Horikoshi N, Sugimachi K, Mitachi Y, Taguchi T. Late phase II study of novel oral fluoropyrimidine anticancer drug S-1 (1 M tegafur–0.4 M Gimestat–1 M Ovastat potassium) in advanced gastric cancer patients. Eur J Cancer. 1998;34:1715–20.
Liu C, Sun Q, Hang X, Zhong B, Wang D. Multicenter phase II study of capecitabine plus oxaliplatin as a first-line therapy in Chinese patients with advanced gastric cancer. Anticancer Drugs. 2008;19:825–31.
Makino T, Fujiwara Y, Takiguchi S, Miyata H, Yamasaki M, Nakajima K, Nishida T, Mori M, Doki Y. The utility of preoperative peritoneal lavage examination in serosa-invading gastric cancer patients. Surgery. 2010;148:96–102.
Yano M, Yasuda T, Fujiwara Y, Takiguchi S, Miyata H, Monden M. Preoperative intraperitoneal chemotherapy for patients with serosa-infiltrating gastric cancer. J Surg Oncol. 2004;88:39–43.
Yamamoto K, Fujiwara Y, Nishida T, Takiguchi S, Nakajima K, Miyata H, Yamasaki M, Mori M, Doki Y. Induction chemotherapy with docetaxel, 5-FU and CDDP (DFP) for advanced gastric cancer. Anticancer Res. 2009;2:4211–5.
Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA; V325 Study Group. 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;24:4991–7.
Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. J Nat Cancer Inst. 2000;92:205–16.
Yoshikawa T, Sasako M, Yamamoto S, Sano T, Imamura H, Fujitani K, Oshita H, Ito S, Kawashima Y, Fukushima N. Phase II study of neoadjuvant chemotherapy and extended surgery for locally advanced gastric cancer. Br J Surg. 2009;96:1015–22.
Okabe H, Ueda S, Obama K, Hosogi H, Sakai Y. Induction chemotherapy with S-1 plus cisplatin followed by surgery for treatment of gastric cancer with peritoneal dissemination. Ann Surg Oncol. 2009;16:3227–36.
Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, Furukawa H, Nakajima T, Ohashi Y, Imamura H, Higashino M, Yamamura Y, Kurita A, Arai K; ACTS-GC Group. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357:1810–20.
Schuhmacher C, Gretschel S, Lordick F, Reichardt P, Hohenberger W, Eisenberger CF, Haag C, Mauer ME, Hasan B, Welch J, Ott K, Hoelscher A, Schneider PM, Bechstein W, Wilke H, Lutz MP, Nordlinger B, Cutsem EV, Siewert JR, Schlag PM. Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954. J Clin Oncol. 2010;28:5210–8.
Li W, Qin J, Sun YH, Liu TS. Neoadjuvant chemotherapy for advanced gastric cancer: a meta-analysis. World J Gastroenterol. 2010;16:5621–8.
Badgwell B, Cormier JN, Krishnan S, Yao J, Staerkel GA, Lupo PJ, Pisters PW, Feig B, Mansfield P. Does neoadjuvant treatment for gastric cancer patients with positive peritoneal cytology at staging laparoscopy improve survival? Ann Surg Oncol. 2008;15:2684–91.
Lorenzen S, Panzram B, Rosenberg R, Nekarda H, Becker K, Schenk U, Höfler H, Siewert JR, Jäger D, Ott K. Prognostic significance of free peritoneal tumor cells in the peritoneal cavity before and after neoadjuvant chemotherapy in patients with gastric carcinoma undergoing potentially curative resection. Ann Surg Oncol. 2010;17:2733–9.
Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008;9:215–21.
Markman M, Bundy BN, Alberts DS, Fowler JM, Clark-Pearson DL, Carson LF, Wadler S, Sickel J. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol. 2001;19:1001–7.
Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, Copeland LJ, Walker JL, Burger RA; Gynecologic Oncology Group. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006;354:34–43.
Ishigami H, Kitayama J, Kaisaki S, Hidemura A, Kato M, Otani K, Kamei T, Soma D, Miyato H, Yamashita H, Nagawa H. Phase II study of weekly intravenous and intraperitoneal paclitaxel combined with S-1 for advanced gastric cancer with peritoneal metastasis. Ann Oncol. 2010;21:67–70.
Fujiwara Y, Nishida T, Takiguchi S, Nakajima K, Miyata H, Yamasaki M, Yamamoto K, Moon JH, Mori M, Doki Y. Feasibility study of S-1 and intraperitoneal docetaxel combination chemotherapy for gastric cancer with peritoneal dissemination. Anticancer Res. 2010;30:1335–9.
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Fujiwara, Y., Takiguchi, S., Nakajima, K. et al. Neoadjuvant Intraperitoneal and Systemic Chemotherapy for Gastric Cancer Patients with Peritoneal Dissemination. Ann Surg Oncol 18, 3726–3731 (2011). https://doi.org/10.1245/s10434-011-1770-8
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DOI: https://doi.org/10.1245/s10434-011-1770-8