Phase I study of biweekly intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel for gastric cancer with peritoneal metastasis.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 139-139
Author(s):  
H. Ishigami ◽  
J. Kitayama ◽  
S. Kaisaki ◽  
H. Yamaguchi ◽  
H. Yamashita ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase I ◽  
Cancer Patients ◽  
Dose Level ◽  
Peritoneal Metastasis ◽  
Phase I Study ◽  
Level 1 ◽  
Grade 3 ◽  
Gastric Cancer Patients ◽  
Experienced Grade

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.

A phase I study of tirapazamine in combination with radiation and weekly cisplatin in patients with locally advanced cervical cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5543-5543
Author(s):  
D. Rischin ◽  
K. Narayan ◽  
A. Oza ◽  
L. Mileshkin ◽  
D. Bernshaw ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Pulmonary Embolism ◽  
Phase I ◽  
Dose Level ◽  
Phase I Study ◽  
Locally Advanced ◽  
Advanced Cervical Cancer ◽  
Locally Advanced Cervical Cancer ◽  
Level 1 ◽  
Grade 3

5543 Background and Purpose: Hypoxia is an adverse prognostic factor in locoregionally advanced cervical cancer treated with radiation. GOG are currently studying the hypoxic cytotoxin, tirapazamine (TPZ) in combination with biweekly intermediate dose cisplatin (CIS) and radiation in a large phase III trial. The aim of this phase I study was to develop a better tolerated regimen that added TPZ to the standard regimen of radiation and weekly low dose CIS. Methods: Eligible patients had previously untreated carcinoma of the cervix, Stages IB2 - IVA. The starting schedule was radiotherapy (45 to 50.4 Gy external beam radiation followed by brachytherapy), with concomitant weekly CIS 40 mg/m2 weeks 1–6 and weekly TPZ 290 mg/m2 (prior to CIS) in weeks 1–5. Results: Between 3/05 and 7/06 eleven patients were enrolled, median age (range) 52 (31–65), squamous cell carcinoma 10, adenocarcinoma 1, 1B2–5, IIA-1, IIB-3, IIIB- 1, IVA-1. The first 2 patients on dose level 1 experienced a dose limiting toxicity (DLT), one grade 3 ALT (SGPT) elevation and grade 4 pulmonary embolism and one grade 3 ototoxicity. Doses were decreased to dose level -1 CIS 30 mg/m2 and TPZ 260 mg/m2. Three patients were treated without any DLTs. Six patients were then treated on dose level -1a, CIS 35 mg/m2 and TPZ 260 mg/m2, with 2 DLTs: grade 3 neutropenia with dose omission and grade 4 pulmonary embolism with major hemodynamic compromise. The sixth patient on dose level -1a withdrew from the trial in week 2 after being advised about the DLTs observed on this dose level. 3 additional patients will be accrued on dose level -1 to confirm safety of this dose level. One patient has relapsed in pelvic nodes, all other patients remain disease-free with a median followup of 10 months (range 5 - 21) Conclusions: The combination of weekly TPZ and CIS with radiation for locally advanced cervical cancer was associated with more toxicity than anticipated with the recommended dose level being TPZ 260 mg/m2, CIS 30 mg/m2. No significant financial relationships to disclose.

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

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.

Phase II study of intraperitoneal paclitaxel combined with S-1 plus cisplatin for gastric cancer with peritoneal metastasis: SP + IP PTX trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4529-4529
Author(s):  
Daisuke Kobayashi ◽  
Ryoji Fukushima ◽  
Mitsuhiko Ota ◽  
Sachio Fushida ◽  
Naoyuki Yamashita ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Phase Ii ◽  
Peritoneal Metastasis ◽  
Response Rate ◽  
Phase Iii ◽  
Peritoneal Cytology ◽  
Response To Chemotherapy ◽  
Grade 3 ◽  
Gastric Cancer Patients

4529 Background: Intraperitoneal (IP) chemotherapy is a promising treatment option for gastric cancer with peritoneal metastasis. Although a phase III study failed to show a statistically significant superiority of IP paclitaxel (PTX) combined with S-1 and intravenous PTX over S-1/cisplatin (SP), the standard of care as a first-line treatment in Japan, the sensitivity analysis suggested clinical efficacy of the IP PTX. Thus, attempts to combine IP PTX with other systemic therapies with higher efficacy have been warranted. After a dose-finding study, we sought to explore efficacy of a new regimen that combined IP PTX with SP. Methods: Gastric cancer patients with peritoneal metastasis confirmed by diagnostic imaging, laparoscopy or laparotomy were enrolled in the phase II multi-institutional prospective trial. In addition to the established SP regimen (S-1 administered orally at a dose of 80 mg/m2 bid for 21 days followed by a 14-day rest and cisplatin administered intravenously at a dose of 60 mg/m2 on day 8), IP PTX was administered on days 1, 8 and 22 at a dose of 20 mg/m2. The primary endpoint is overall survival (OS) rate at one year after treatment initiation. Secondary endpoints are progression free survival (PFS), response rate and toxicity. Results: Fifty-three patients were enrolled and fully evaluated for OS and toxicity. The median number of courses was 7 (range 1-20). The 1-year OS rate was 74% (95% CI, 60-83%). The median survival time was 19.4 months (95% CI, 16.7 months-). The 1-year PFS rate was 57% (95% CI, 42-69%). The overall response rate was 20% (95% CI, 1-72%) in 5 patients with target lesions. Cancer cells ceased to be detected by peritoneal cytology in 23 (64%) of 36 patients. Fourteen (26%) patients underwent gastrectomy after response to chemotherapy. The incidences of grade 3/4 hematological and non-hematological toxicities were 43% and 47%, respectively. The frequent grade 3/4 toxicities included neutropenia (23%), anemia (29%), diarrhea (13%) and anorexia (17%). Intraperitoneal catheter and implanted port-related complications were observed in 4 patients. There was 1 treatment-related death. Conclusions: IP PTX combined with SP is well tolerated and active in gastric cancer patients with peritoneal metastasis. Clinical trial information: UMIN000023000 .

Phase I dose-finding study of sorafenib in combination with capecitabine and cisplatin as a first-line treatment in patients with advanced gastric cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4559-4559
Author(s):  
C. Kim ◽  
J. Lee ◽  
Y. Choi ◽  
B. Kang ◽  
M. Ryu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase I ◽  
Dose Level ◽  
Dose Finding ◽  
Finding Study ◽  
Level 3 ◽  
Dose Finding Study ◽  
Level 1 ◽  
Grade 3 ◽  
Level 2

4559 Background: We conducted a phase I dose-finding study of sorafenib (S) in combination with capecitabine (X) and cisplatin (P) in patients with previously untreated metastatic or inoperable advanced gastric cancer. Methods: Four dose levels of S, X, and P combination were tested. The doses of S (p.o. daily), X (p.o. on days 1–14), and P (i.v. on day 1) were escalated at the following schedule; level 1: S 400 mg/d, X 1,600 mg/m2/d, P 80 mg/m2; level 2: S 800 mg/d, X 1,600 mg/m2/d, P 80 mg/m2; level 3: S 800 mg/d, X 2,000 mg/m2/d, P 80 mg/m2; level 1A: S 800 mg/d, X 1,600 mg/m2/d, P 60 mg/m2. The cycle was repeated every 3 weeks. Dose limiting toxicities (DLTs) were evaluated only in the first cycles and a standard 3+3 dose escalation design was implemented. Results: A total 21 pts were enrolled in the study. No DLTs were observed at dose level 1 (n=3). One DLT (grade 3 diarrhea) was noted at dose level 2 (n=6), and 2 DLTs (two grade 4 neutropenias longer than 5 days in duration) were observed at dose level 3 (n=6), which made the level 3 dose the maximum tolerated dose (MTD). However, at cycle 2 and thereafter at dose level 2, the relative dose intensity (RDI) of S and X could not be maintained (mostly below 80%) due to the frequent dose reductions and cycle delays. So, we explored a new dose level (1A) between dose level 1 and 2. Since no DLTs were found in 6 patients at level 1A with RDI mostly above 80% throughout the treatment period, level 1A was determined as recommended dose (RD). Most frequent grade 3 and 4 hematologic toxicities were neutropenia (25.0% of cycles), and most frequent grade 2 and 3 non-hematologic toxicities were hand-foot syndrome (9.4%), asthenia (7.0%), and anorexia (5.5%). The objective responses were confirmed in 10 out of 16 patients with measurable lesions (62.5%; 95% CI, 38.8–86.2%). With a median follow-up of 8.1 months, estimated median progression-free survival was 10.0 months (95% CI, 1.6–18.4 months) and median overall survival has not been reached. Conclusions: Diarrhea and neutropenia were DLTs in this S, X, and P combination. The dose schedule of sorafenib 400 mg po bid daily with capecitabine 800 mg/m2 po bid on days 1–14, and cisplatin 60 mg/m2 iv on day 1 in every 3 weeks is recommended for further development in AGC. [Table: see text]

Phase II study of weekly intravenous and intraperitoneal paclitaxel combined with S-1 for advanced gastric cancer with peritoneal metastasis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4542-4542
Author(s):  
H. Ishigami ◽  
J. Kitayama ◽  
S. Kaisaki ◽  
A. Hidemura ◽  
M. Kato ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Peritoneal Metastasis ◽  
Response Rate ◽  
Peritoneal Dissemination ◽  
Phase Ii Study ◽  
Malignant Ascites ◽  
Peritoneal Cytology ◽  
Grade 3 ◽  
Gastric Cancer Patients

4542 Background: A phase II study to evaluate the efficacy and tolerability of weekly intravenous and intraperitoneal paclitaxel combined with S-1 was performed in gastric cancer patients with peritoneal metastasis. Methods: Gastric cancer patients with peritoneal dissemination and/or cancer cells on peritoneal cytology were enrolled. Paclitaxel was administered intravenously at 50 mg/m2 and intraperitoneally at 20 mg/m2 on days 1 and 8. S-1 was administered at 80 mg/m2/day for 14 consecutive days, followed by 7 days rest. The primary endpoint was the 1-year overall survival rate. Secondary endpoints were the response rate, efficacy against malignant ascites and safety. Results: Forty patients were enrolled, including 21 with primary tumors with peritoneal dissemination confirmed by staging laparoscopy, 13 with peritoneal recurrence, and 6 with positive peritoneal cytology only. The median number of courses administered was 7 (range 1–23). The 1-year overall survival rate was 78% (95% CI, 65–90%). The overall response rate was 56% (95% CI, 32–79%) in 18 patients with target lesions. Malignant ascites disappeared or decreased in 13 of 21 (62%) patients. The incidences of grade 3/4 hematological and non- hematological toxicities were 40% and 15%, respectively. The frequent grade 3/4 toxicities included neutropenia (38%), leukopenia (18%), anemia (10%), and nausea (8%). Catheter obstruction observed in one patient was the only complication related to the peritoneal access device or intraperitoneal infusion. There were no treatment-related deaths. Conclusions: Combination chemotherapy of intravenous and intraperitoneal paclitaxel with S-1 is well tolerated and active in gastric cancer patients with peritoneal metastasis. No significant financial relationships to disclose.

Phase I study of weekly intraperitoneal paclitaxel combined with S-1 and oxaliplatin for gastric cancer with peritoneal metastasis.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 146-146 ◽  
Author(s):  
Hironori Ishigami ◽  
Shoichi Kaisaki ◽  
Hironori Yamaguchi ◽  
Hiroharu Yamashita ◽  
Shigenobu Emoto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase I ◽  
Dose Level ◽  
Phase Ii ◽  
Peritoneal Metastasis ◽  
Hematological Toxicity ◽  
Phase Ii Studies ◽  
Level 3 ◽  
Grade 3 ◽  
Dose Levels

146 Background: Intraperitoneal (IP) chemotherapy is a promising treatment option for gastric cancer with peritoneal metastasis. We previously verified the safety and efficacy of IP paclitaxel (PTX) combined with S-1 and intravenous PTX in phase I and phase II studies. S-1 plus oxaliplatin (SOX) demonstrated efficacy in a phase II study, and is regarded as a candidate for the next-generation standard regimen for gastric cancer. We designed a new regimen combining weekly IP PTX with SOX in order to maximize systemic effects as well as local effects in the peritoneal cavity. A dose-escalation study of IP PTX in combination with fixed doses of SOX was carried out to determine the maximum-tolerated dose (MTD) and recommended dose (RD). Methods: PTX was administered intraperitoneally on days 1 and 8 with an initial dose of 20 mg/m2 (level 1), stepped up to 30 mg/m2 (level 2) or 40 mg/m2 (level 3) depending on observed toxicity. S-1 was administered orally at a dose of 80 mg/m2/day (b.i.d.) for 14 days followed by a 7-day rest. Oxaliplatin was administered intravenously at a dose of 100 mg/m2 on day 1. This treatment was repeated every 3 weeks. Toxicity was graded according to CTCAE v4.0. Dose-limiting toxicities (DLTs) were defined as grade 4 leukopenia, grade 3 febrile neutropenia, grade 3 thrombocytopenia, and grade 3 non-hematological toxicity. The MTD was defined as the dose level at which 2 or more of 3 or 6 patients developed DLTs during two courses of treatment. The RD was defined as one dose level under the MTD. Results: A total of 12 gastric cancer patients with peritoneal metastasis were enrolled. No DLTs were observed at all dose levels. Neutropenia in one patient at dose level 3 was the only grade 3 toxicity observed. Grade 2/3 leukopenia, neutropenia and thrombocytopenia were observed only in 2 patients at dose level 3. Regarding grade 2 non-hematological toxicities, anorexia, fatigue and nausea were observed in 6, 4 and 2 patients, respectively, independent of dose levels. Consequently, the MTD was not reached, and the RD of IP PTX was determined to be 40 mg/m2 (level 3). Conclusions: Combination chemotherapy of IP PTX with SOX was shown to be a safe regimen that should be further explored in clinical trials.

Phase II study of intraperitoneal docetaxel plus capecitabine/cisplatin for gastric cancer with peritoneal metastasis: XP+IP DOC trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4039-4039 ◽  
Author(s):  
Ryoji Fukushima ◽  
Hironori Ishigami ◽  
Hiroto Miwa ◽  
Motohiro Imano ◽  
Daisuke Kobayashi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Phase Ii ◽  
Peritoneal Metastasis ◽  
Phase Ii Study ◽  
Median Number ◽  
Peritoneal Cytology ◽  
Response To Chemotherapy ◽  
Grade 3 ◽  
Gastric Cancer Patients

4039 Background: Intraperitoneal (IP) chemotherapy with taxanes provides sustained high local concentrations, and the efficacy of IP paclitaxel (PTX) has been shown in ovarian cancer. We previously reported the safety and efficacy of IP PTX plus systemic chemotherapy in clinical trials. Capecitabine/cisplatin (XP) is one of the standard regimens for the first-line treatment of advanced gastric cancer worldwide. We designed a new regimen combining IP docetaxel (DOC) with XP, and the recommended dose of IP DOC was determined to be 10 mg/m2 in a phase I study. A phase II study of XP plus IP DOC was performed in gastric cancer patients with peritoneal metastasis. Methods: Gastric cancer patients with peritoneal metastasis confirmed by diagnostic imaging, laparoscopy or laparotomy were enrolled. DOC was administered intraperitoneally at 10 mg/m2 on days 1 and 8. Cisplatin was administered intravenously at 80 mg/m2 on day 1, and capecitabine was administered at 1000 mg/m2 bid for 14 consecutive days, repeated every 21 days. The primary endpoint was the 1-year overall survival (OS) rate. Secondary endpoints were response rate, negative conversion rate on peritoneal cytology and safety. Results: Out of 50 patients enrolled, 48 patients received protocol treatment, and were evaluated for OS and toxicity. The median number of courses was 6 (range 1-15). The 1-year OS rate was 75% (95% confidence interval, 60-85%). The best overall response was stable disease in all the three patients with target lesions. Cancer cells ceased to be detected by peritoneal cytology in 28 (76%) of 37 patients. Nineteen patients underwent gastrectomy after response to chemotherapy. The incidences of grade 3/4 hematological and non-hematological toxicities were 42% and 48%, respectively. The frequent grade 3/4 toxicities included neutropenia (21%), leukopenia (8%), anemia (29%), anorexia (25%) and nausea (17%). Infection of the intraperitoneal port was observed in one patient. There were no treatment-related deaths. Conclusions: Combination chemotherapy of XP plus IP DOC regimen is well tolerated and active in gastric cancer patients with peritoneal metastasis. Clinical trial information: UMIN000016469.

scholarly journals Phase I study of the 177Lu-DOTA0-Tyr3-Octreotate (lutathera) in combination with nivolumab in patients with neuroendocrine tumors of the lung

2020 ◽  
Vol 8 (2) ◽  
pp. e000980
Author(s):  
Chul Kim ◽  
Stephen V Liu ◽  
Deepa S Subramaniam ◽  
Tisdrey Torres ◽  
Massimo Loda ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Level ◽  
Neuroendocrine Tumors ◽  
Phase I Study ◽  
Somatostatin Receptors ◽  
Atypical Carcinoid ◽  
Platinum Based Chemotherapy ◽  
Level 1 ◽  
Grade 3 ◽  
Level 2

BackgroundLutathera is a 177Lutetium-labeled somatostatin analog approved for the treatment of gastroenteropancreatic neuroendocrine tumors (NETs). Somatostatin receptors are expressed in small cell lung cancer (SCLC). Nivolumab, an anti-PD-1 antibody, may act synergistically with lutathera to generate antitumor immunity. We conducted a phase I study of lutathera plus nivolumab in patients with advanced NETs of the lung.MethodsPatients with relapsed/refractory extensive-stage SCLC (ES-SCLC), non-progressing ES-SCLC after first-line platinum-based chemotherapy, or advanced grade I-II pulmonary NETs were eligible. The primary objective was to determine the recommended phase 2 dose (RP2D). The phase I portion followed a standard 3+3 design, assessing two dose levels (dose level 1: lutathera 3.7 GBq every 8 weeks for four doses with nivolumab 240 mg every 2 weeks; dose level 2: lutathera 7.4 GBq every 8 weeks for four doses with nivolumab 240 mg every 2 weeks).ResultsNine patients were enrolled (six ES-SCLC, two pulmonary atypical carcinoid, one high-grade pulmonary neuroendocrine carcinoma). No dose-limiting toxicities (DLTs) were observed at dose level 1. At dose level 2, one patient with refractory ES-SCLC developed a DLT (grade 3 rash). The most common treatment-related adverse events (TRAEs) were lymphopenia (n=7), thrombocytopenia (n=4), anemia (n=3), and nausea (n=3). The most common grade 3 TRAE was lymphopenia (n=4). Among the seven patients with measurable disease, one patient with ES-SCLC had a partial response. Two patients with pulmonary atypical carcinoid had stable disease lasting 6 months. The RP2D was dose level 2.ConclusionsLutathera plus nivolumab was well tolerated and showed signs of antitumor activity. This combination warrants further exploration.Trial registration numberNCT03325816

Phase 1 Study of Combined Chemotherapy of Nab-Paclitaxel, S-1, and Oxaliplatin for Gastric Cancer with Peritoneal Metastasis (NSOX Study)

Oncology ◽  
2020 ◽  
Vol 99 (1) ◽  
pp. 57-61
Author(s):  
Masaki Nakamura ◽  
Toshiyasu Ojima ◽  
Masahiro Katsuda ◽  
Keiji Hayata ◽  
Junya Kitadani ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dose Level ◽  
Peritoneal Metastasis ◽  
Phase 1 ◽  
Maximum Tolerated Dose ◽  
Antitumor Effects ◽  
Phase 1 Study ◽  
Tumor Tissues ◽  
Level 1 ◽  
Gastric Cancer Patients

<b><i>Objectives:</i></b> A regimen of S-1 combined with oxaliplatin (SOX) has been widely used as the first-line regimen for advanced gastric cancer. To further improve the antitumor efficacy for gastric cancer patients with peritoneal metastasis, we added nab-paclitaxel to the established SOX regimen (NSOX). Nab-paclitaxel (nanoparticle albumin-bound paclitaxel) has effective transferability to tumor tissues and strong antitumor effects for peritoneal metastasis. We performed a phase 1 study of this regimen to determine the maximum tolerated dose (MTD) and the recommended dose (RD) in patients with gastric cancer with peritoneal metastasis. <b><i>Methods:</i></b> The NSOX regimen involved 21-day cycles with escalated doses of nab-paclitaxel (50 [level 1] to 80 [level 4] mg/m<sup>2</sup> on days 1 and 8) and fixed doses of oxaliplatin (100 mg/m<sup>2</sup> on day 1) and S-1 (80 mg/m<sup>2</sup>/day for 2 weeks). <b><i>Results:</i></b> Six patients with gastric cancer with peritoneal metastasis were enrolled. The MTD was determined to be dose level 2, as 2 of 3 patients experienced dose-limiting toxicities (DLTs), grade 4 non-hematological toxicities. One patient experienced acute myocardial infarction, and the other patient developed jejunal perforation. There were no treatment-related deaths. No patients experienced DLTs, so the RD was determined to be dose level 1. <b><i>Conclusions:</i></b> The NSOX regimen was shown to be a tolerable regimen and may be a promising triplet therapy for patients with gastric cancer with peritoneal metastasis.

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