Phase I study of postoperative radiotherapy concurrent with S-1 in patients with gastric cancer

139 Background: Intraperitoneal (IP) chemotherapy is promising for the treatment of gastric cancer with peritoneal metastasis. We previously verified the safety and efficacy of IP paclitaxel (PTX) combined with S-1 and intravenous (IV) PTX in phase I and phase II studies (Oncology. 2009; Ann Oncol. 2010). Secondly, we developed a new IP-containing chemotherapy regimen, IV PTX plus IP cisplatin (CDDP) and PTX, for patients who have failed S-1-based chemotherapy. We performed a phase I study to determine the maximum-tolerated dose (MTD) and recommended dose (RD) in gastric cancer patients. Methods: A total of 9 gastric cancer patients were enrolled who had shown progression of peritoneal metastasis after S-1-based chemotherapy. PTX was administered intravenously at a dose of 100 mg/m2 and intraperitoneally over 1 hour with an initial dose of 20 mg/m2 (level 1), stepped up to 30 or 40 mg/m2 depending on observed toxicity. CDDP was subsequently administered intraperitoneally at a dose of 30 mg/m2 over 24 hours after PTX infusion. PTX and CDDP were administered on days 1 and 15 in 4-week cycles. Results: At dose level 1, dose-limiting toxicities (DLTs) were observed in 2 of 3 patients. One patient experienced grade 4 leukopenia, and the other grade 3 vomiting. Because of higher toxicities than anticipated, the initial dose-escalation schedule was abandoned, and the doses of IV PTX and IP CDDP were reduced to 80 mg/m2 and 25 mg/m2, respectively, while keeping the dose of IP PTX at 20 mg/m2 (level 0). At dose level 0, one of the first 3 patients experienced grade 3 nausea, and an additional 3 patients experienced no DLTs. Consequently, the MTD and RD were determined to be dose level 1 and dose level 0, respectively. No patients experienced complications related to the peritoneal access device or IP infusion. Conclusions: Combination chemotherapy of IV PTX plus IP CDDP and PTX was shown to be a safe regimen that should be further explored in clinical trials. No significant financial relationships to disclose.

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The quality of life (QoL) assessment of oxaliplatin-based preoperative chemotherapy for locally advanced gastric cancer: An integration analysis of two prospective phase I study.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e18263 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e18263-e18263

Author(s):

Hironaga Satake ◽

Akira Miki ◽

Hisateru Yasui ◽

Akihito Tsuji

Keyword(s):

Gastric Cancer ◽

Lymph Node ◽

Neoadjuvant Chemotherapy ◽

Phase I ◽

Advanced Gastric Cancer ◽

Phase I Study ◽

Locally Advanced ◽

Node Dissection ◽

Locally Advanced Gastric Cancer ◽

Prospective Phase

e18263 Background: Surgery with lymph node dissection is the primary treatment for patients with localized resectable gastric cancer. However, the prognosis of locally advanced gastric cancer is poor. One promising approach is neoadjuvant chemotherapy, however, the use of neoadjuvant chemotherapy consisting of oxaliplatin-based regimen for locally advanced gastric cancer has not been reported. Oxaliplatin-induced neurotoxicity may continue after the chemotherapy and interfere with patients’ daily activities. We conducted two prospective phase I study of oxaliplatin-based neoadjuvant chemotherapy for locally advanced gastric cancer and assessed the oxaliplatin-induced neuropathy using the FACT-Ga and FACT-GOG-Ntx assessments. Methods: We planned two cycles of oxaliplatin administration and evaluated oxaliplatin-induced neuropathy using the FACT-Ga and FACT-GOG-Ntx assessments. Patients with locally advanced gastric cancer received two cycles of neoadjuvant chemotherapy with oxaliplatin (100 or 130 mg/m2) on day 1, as well as S-1 (80 mg/m2/day, b.i.d.) or capecitabine (2000 mg/m2/day, b.i.d.) for 14 days, repeated every 3 weeks. They then underwent gastrectomy with curative D2/3 lymph-node dissection followed by adjuvant S-1 (80 mg/m2/day, b.i.d.) for one year. QoL was assessed at baseline and during treatment. Results: Twelve patients were enrolled and fully assessed the QoL. All patients were chmo-naïve and had a good performance status: median age 70y, 67% male. The mean dose intensity of delivered during the neoadjuvant chemotherapy was 96.0% for oxaliplatin. Peripheral neuropathy was observed in all patients but with no functional disorders. Median time to QoL deterioration in FACT-G and FACT-GOG-NTx was 3 weeks. There were correlation between oxaliplatin administration and QoL deterioration by the repeated-measures ANOVA. Conclusions: FACT-GOG-Ntx showed that sensory neuropathy caused a deterioration in QoL immediately after the initiation of preoperative oxaliplatin-based chemotherapy, but that QoL recovered after the neo-adjuvant chemotherapy. Clinical trial information: UMIN000015950,UMIN000015181.

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A dose-finding study for irinotecan, cisplatin, and S-1 (IPS) in patients with advanced gastric cancer (OGSG 1106).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.144 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 144-144

Author(s):

Hiroki Yukami ◽

Masahiro Goto ◽

Takayuki Kii ◽

Tetsuji Terazawa ◽

Toshifumi Yamaguchi ◽

...

Keyword(s):

Gastric Cancer ◽

Antitumor Activity ◽

Febrile Neutropenia ◽

Phase I ◽

Advanced Gastric Cancer ◽

Phase I Study ◽

Fixed Dose ◽

Level 1 ◽

Grade 3 ◽

Level 2

144 Background: In Japan, S-1 plus cisplatin is regarded as one of the standard first line treatment of advanced gastric cancer (AGC). However, the prognosis of AGC remains dismal. The development of more effective chemotherapeutic regimen is thus warranted. A combination of irinotecan, cisplatin, and S-1 (IPS) can be a promising triplet therapy for advanced gastric cancer. We conducted a phase I study of IPS to determine the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD) and recommended dose (RD), and to assess its safety and antitumor activity in patients with AGC. Methods: This phase I study was designed and conducted in a 3 + 3 manner to determine the recommended dose (RD) of IPS for the subsequent phase II study. Patients received an escalating dose of intravenous irinotecan (level 1: 100/level 2: 125/level 3: 150 mg/m²) on day 1, a fixed dose of intravenous cisplatin (60 mg/m²) on day 1, a fixed dose of S-1 (80 mg/m² b.i.d.) orally on days 1-14, every 4 weeks. Results: Twelve patients were enrolled between June 2013 and February 2017. During the first cycle, one of the six patients in level 1 and two of six patients in level 2 developed the DLT (grade 4 leucocytopenia and grade 3 febrile neutropenia). The MTD of irinotecan was 125 mg/m 2 (level 2) and the RD of irinotecan was considered to be 100 mg/m² (level 1). The most common grade 3 or 4 adverse events included neutropenia 75 % (9/12), anemia 25% (3/12), anorexia 8% (1/12), and febrile neutropenia 17% (2/12). Among six patients with measurable lesions, the response rate was 66.7% (4/6) [95% CI, 33.3-90.7%]. Two patients were performed R0 resection after IPS, with one patient achieved pathological complete response. The median survival time is under analysis. Conclusions: RD of IPS was determined to be 100 mg/m² of irinotecan, 60 mg/m² of cisplatin, and 80 mg/m² of S-1. Our data showed that this regimen provided acceptable antitumor activity and a favorable toxicity profile. Further evaluation of this regimen is warranted. Clinical trial information: UMIN000006864.

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