|
1
|
Lin JX, Tang YH, Zheng HL, Ye K, Cai JC, Cai LS, Lin W, Xie JW, Wang JB, Lu J, Chen QY, Cao LL, Zheng CH, Li P, Huang CM. Neoadjuvant camrelizumab and apatinib combined with chemotherapy versus chemotherapy alone for locally advanced gastric cancer: a multicenter randomized phase 2 trial. Nat Commun 2024; 15:41. [PMID: 38167806 PMCID: PMC10762218 DOI: 10.1038/s41467-023-44309-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Accepted: 12/07/2023] [Indexed: 01/05/2024] Open
Abstract
Prospective evidence regarding the combination of programmed cell death (PD)-1 and angiogenesis inhibitors in treating locally advanced gastric cancer (LAGC) is limited. In this multicenter, randomized, phase 2 trial (NCT04195828), patients with gastric adenocarcinoma (clinical T2-4N + M0) were randomly assigned (1:1) to receive neoadjuvant camrelizumab and apatinib combined with nab-paclitaxel plus S-1 (CA-SAP) or chemotherapy SAP alone (SAP) for 3 cycles. The primary endpoint was the major pathological response (MPR), defined as <10% residual tumor cells in resection specimens. Secondary endpoints included R0 resection rate, radiologic response, safety, overall survival, and progression-free survival. The modified intention-to-treat population was analyzed (CA-SAP [n = 51] versus SAP [n = 53]). The trial has met pre-specified endpoints. CA-SAP was associated with a significantly higher MPR rate (33.3%) than SAP (17.0%, P = 0.044). The CA-SAP group had a significantly higher objective response rate (66.0% versus 43.4%, P = 0.017) and R0 resection rate (94.1% versus 81.1%, P = 0.042) than the SAP group. Nonsurgical grade 3-4 adverse events were observed in 17 patients (33.3%) in the CA-SAP group and 14 (26.4%) in the SAP group. Survival results were not reported due to immature data. Camrelizumab and apatinib combined with chemotherapy as a neoadjuvant regimen was tolerable and associated with favorable responses for LAGC.
Collapse
Affiliation(s)
- Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Yi-Hui Tang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Hua-Long Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Kai Ye
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Jian-Chun Cai
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China
| | - Li-Sheng Cai
- Department of General Surgery, Zhangzhou Municipal Hospital of Fujian Province, Zhangzhou, China
| | - Wei Lin
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Putian University, Putian, China
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Jia-Bin Wang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Jun Lu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Long-Long Cao
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
| |
Collapse
|
|
2
|
Abudureheiyimu N, Wu Y, Li Q, Zhang P, Ma F, Yuan P, Luo Y, Fan Y, Chen S, Cai R, Li Q, Han Y, Xu H, Wang Y, Wang J, Xu B. Docetaxel plus S-1 versus docetaxel plus capecitabine as first-line treatment for advanced breast cancer patients: a prospective randomized phase II study. JOURNAL OF THE NATIONAL CANCER CENTER 2023; 3:115-120. [PMID: 39035725 PMCID: PMC11256714 DOI: 10.1016/j.jncc.2023.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 04/24/2023] [Accepted: 05/17/2023] [Indexed: 07/23/2024] Open
Abstract
Background This study was conducted to evaluate the efficacy and safety of docetaxel/S-1 (TS) compared with docetaxel/capecitabine (TX) as a first-line treatment for advanced breast cancer. Methods Patients with advanced metastatic breast cancer were randomly divided into the TS group (n = 54) and the TX group (n = 57) for first-line chemotherapy from August 2015 to April 2019 (ClinicalTrials.org registration no. NCT02947061). Following the completion of combination therapy, patients without progression received S-1 or capecitabine maintenance treatment. The primary end point was progression-free survival (PFS). Results Among 111 enrolled patients, the median PFS did not differ significantly between the TS group and the TX group (TS vs. TX, 9.0 vs. 7.4 months, P = 0.365, 95% confidence interval [CI]: 0.50-1.11, hazard ratio [HR]: 0.75). There was also no statistically significant difference in median overall survival (OS) between the two groups (TS vs. TX, 40.2 vs. 41.3 months, P = 0.976). In addition, visceral metastasis and metastasis sites, such as the liver or lung, did not lead to a significant effect on PFS and OS. The two regimens showed no significant difference in adverse events, except hand-foot syndrome, which predominated in the TX group (38.6% vs. 7.4%, P = 0.001), and diarrhea (24.1% vs. 3.6%, P = 0.003) and elevation of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels (14.8% vs. 3.5%, P = 0.049), which were more frequent in the TS group. Conclusions The TS and TX regimens demonstrated similar efficacy and safety for the first-line treatment of advanced breast cancer. The TS regimen had fewer cases of severe hand-foot syndrome than the TX regimen, representing an effective alternative option to the TX regimen. Further studies are warranted to define the efficacy and safety of this strategy in real-world settings.
Collapse
Affiliation(s)
- Nilupai Abudureheiyimu
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yun Wu
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qing Li
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Pin Zhang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fei Ma
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Peng Yuan
- Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yang Luo
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ying Fan
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shanshan Chen
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ruigang Cai
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qiao Li
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yiqun Han
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hangcheng Xu
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yan Wang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jiayu Wang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Binghe Xu
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| |
Collapse
|
|
3
|
Sato S, Kunisaki C, Tanaka Y, Sato K, Miyamoto H, Yukawa N, Kosaka T, Akiyama H, Endo I, Misumi T. Curative-Intent Surgery for Stage IV Advanced Gastric Cancer: Who Can Undergo Surgery and What Are the Prognostic Factors for Long-Term Survival? Ann Surg Oncol 2019; 26:4452-4463. [PMID: 31529308 DOI: 10.1245/s10434-019-07790-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND A retrospective study was performed to evaluate the predictive factors for performing curative-intent surgery and prognostic factors for long-term survival of patients undergoing surgery for stage IV gastric cancer. PATIENTS AND METHODS Between 2001 and 2017, 271 patients with stage IV gastric cancer with distant metastasis who underwent systemic chemotherapy were enrolled. Logistic regression analysis was performed to evaluate predictive factors for curative-intent surgery. Cox proportional hazards regression model was applied for patients who were subsequently treated with curative-intent surgery to identify prognostic factors for long-term survival. RESULTS Curative-intent surgery was performed in 48 patients (17.7%). Median survival time was significantly longer in the surgery group than in the nonsurgery group (53 vs. 11 months, p < 0.0001). R0 resection was performed in 35 patients (72.9%). The three-year overall survival (OS) rates of the R0, R1, and R2 surgery groups were 75.4%, 33.3%, and 25.0%, respectively (p = 0.0002). Logistic regression analysis revealed that lymphogenous distant metastasis alone (odds ratio = 3.276, p = 0.004), positive lavage cytology alone (6.394, 0.014), doublet or triplet chemotherapy (4.064, 0.034), and high Glasgow prognostic score (0.276, 0.001) were independent predictive factors for performing curative-intent surgery. Among patients undergoing surgery, the Cox proportional hazards regression model for OS showed that R0 surgery was an independent prognostic factor for favorable OS (hazard ratio 0.188, p = 0.022). CONCLUSIONS Patients with lymphogenous distant metastasis alone, P0CY1 alone, good immunonutritional status, and doublet/triplet chemotherapy are candidates for performing effective curative-intent surgery. R0 surgery is crucial for improving long-term survival after surgery.
Collapse
Affiliation(s)
- Sho Sato
- Department of Surgery, Gastroenterological Center, Yokohama City University, Yokohama City, Kanagawa, Japan.,Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama City, Kanagawa, Japan
| | - Chikara Kunisaki
- Department of Surgery, Gastroenterological Center, Yokohama City University, Yokohama City, Kanagawa, Japan.
| | - Yusaku Tanaka
- Department of Surgery, Gastroenterological Center, Yokohama City University, Yokohama City, Kanagawa, Japan
| | - Kei Sato
- Department of Surgery, Gastroenterological Center, Yokohama City University, Yokohama City, Kanagawa, Japan
| | - Hiroshi Miyamoto
- Department of Surgery, Gastroenterological Center, Yokohama City University, Yokohama City, Kanagawa, Japan
| | - Norio Yukawa
- Department of Surgery, Gastroenterological Center, Yokohama City University, Yokohama City, Kanagawa, Japan
| | - Takashi Kosaka
- Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama City, Kanagawa, Japan
| | - Hirotoshi Akiyama
- Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama City, Kanagawa, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama City, Kanagawa, Japan
| | - Toshihiro Misumi
- Department of Biostatistics, School of Medicine, Yokohama City University, Yokohama City, Kanagawa, Japan
| |
Collapse
|
|
4
|
Can the Neutrophil to Lymphocyte Ratio Be Used to Determine Gastric Cancer Treatment Outcomes? A Systematic Review and Meta-Analysis. DISEASE MARKERS 2016; 2016:7862469. [PMID: 26924872 PMCID: PMC4746375 DOI: 10.1155/2016/7862469] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/09/2015] [Accepted: 12/31/2015] [Indexed: 12/12/2022]
Abstract
The prognostic role of neutrophil to lymphocyte ratio (NLR) in gastric cancer remains controversial. We aimed to quantify the prognostic role of peripheral blood NLR in gastric cancer. A literature search was conducted in PubMed, EMBASE, and Cochrane databases. The results for overall survival (OS) and progression-free survival (PFS)/disease-free survival (DFS) are expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). 19 studies with 5431 patients were eligible for final analysis. Elevated NLRs were associated with a significantly poor outcome for OS (HR = 1.98; 95% CI: 1.75–2.24, p < 0.001) and PFS (HR = 1.58; 95% CI: 1.32–1.88, p < 0.001) compared with patients who had normal NLRs. The NLR was higher for patients with late-stage compared with early-stage gastric cancer (OR = 2.76; 95% CI: 1.36–5.61, p = 0.005). NLR lost its predictive role for patients with stage IV gastric cancer who received palliative surgery (HR = 1.73; 95% CI: 0.85–3.54, p = 0.13). Our results also indicated that prognoses might be influenced by the NLR cutoff values. In conclusion, elevated pretreatment NLRs are associated with poor outcome for patients with gastric cancer. The ability to use the NLR to evaluate the status of patients may be used in the future for personalized cancer care.
Collapse
|
|
5
|
A phase II study of biweekly S-1 and paclitaxel (SPA) as first-line chemotherapy in patients with metastatic or advanced gastric cancer. Cancer Chemother Pharmacol 2015; 76:197-203. [PMID: 26013324 DOI: 10.1007/s00280-015-2782-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Accepted: 05/18/2015] [Indexed: 10/23/2022]
Abstract
PURPOSE Paclitaxel and S-1 are both effective antitumor chemotherapeutic agents for advanced gastric cancer. However, the continuous administration of S-1 for 3 weeks or more can result in unacceptable toxicities, particularly hematological toxicities. Therefore, an alternative treatment schedule (1-week administration followed by 1-week rest) is warrant for testing in order to allow continuation of the therapy. We evaluate the efficacy and safety of biweekly S-1 and paclitaxel (SPA) as first-line chemotherapy in patients with metastatic or advanced gastric cancer. METHODS Patients with previously untreated advanced or relapsed gastric cancer who had measurable lesion(s) were enrolled. Paclitaxel was administered intravenously at a dose of 120 mg/m(2) on day 1 and oral S-1 was given twice daily (BSA < 1.25 m(2), 80 mg/day; 1.25 ≤ BSA < 1.50 m(2), 100 mg/day; 1.50 m(2) ≤ BSA, 120 mg/day) on days 1-7 followed by a drug-free interval of 1 week every 14-day cycle. RESULTS Forty-four patients (M/F = 33/11) were enrolled. A total of 277 chemotherapy cycles were administered, with a median of six cycles per patient (range 1-12), and 19 (43.2 %) patients received up to seven cycles. The assessed overall response rate was 38.6 with 38.6 % partial response in 17 patients, 45.4 % stable disease in 20 patients, and 13.6 % progressive disease in six patients. Thirty-four patients (77.3 %) received second-line chemotherapy. The estimated median progression-free survival and median overall survival times were, respectively, 5.2 months (95 % CI 4.08-6.39 months) and 12.2 months (95 % CI 8.81-15.60 months). The major hematological toxicities were included grade 3 leucocytopenia in two patients (4.5 %), grade 3 neutropenia in 14 patients (40.9 %), and grade 4 neutropenia in four patients (9.0 %). Two patients (4.5 %) suffered grade 1 febrile neutropenia. All grade of the non-hematological toxicities, such as nausea, vomiting, alopecia, and diarrhea, held the proportion of 54.5 % (grade 3/4, 4.5 %), 31.8, 95.4, and 18.1 % (grade 3/4, 2.2 %), respectively. CONCLUSIONS Biweekly S-1 and paclitaxel (SPA regimen) combination therapy had promising activity with acceptable adverse toxicities. SPA regimen was easily implemented, and more patients received second-line chemotherapy. It deserved to conduct a well-designed randomized phase III study to compare this regimen with S-1-based combination treatment.
Collapse
|
|
6
|
Yang J, Zhou Y, Min K, Yao Q, Xu CN. S-1-based vs non-S-1-based chemotherapy in advanced gastric cancer: A meta-analysis. World J Gastroenterol 2014; 20:11886-11893. [PMID: 25206296 PMCID: PMC4155382 DOI: 10.3748/wjg.v20.i33.11886] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2014] [Revised: 04/24/2014] [Accepted: 05/26/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the efficacy and tolerability of S-1-based vs non-S-1-based chemotherapy in advanced gastric cancer (AGC).
METHODS: We extracted reported endpoints, including overall survival (OS), progression-free survival (PFS), time-to-treatment failure (TTF), objective response rate (ORR) and adverse effects, from randomized controlled trials identified in PubMed, the Cochrane library, Science Direct, EMBASE and American Society of Clinical Oncology meetings. Stata software was used to calculate the pooled values.
RESULTS: Seven randomized controlled trials involving 2176 patients were included in this meta-analysis. Compared to non-S-1-based regimens, the use of S-1-based regimens were associated with an increase in ORR (RR = 1.300; 95%CI: 1.028-1.645); OS (HR = 0.89; 95%CI: 0.81-0.99; P = 0.025), TTF (HR = 0.83; 95%CI: 0.75-0.92; P = 0.000), and a lower risk of febrile neutropenia (RR = 0.225; P = 0.000) and stomatitis (RR = 0.230; P = 0.032). OS, PFS and TTF were prolonged, especially in the Asian population. In subgroup analysis, statistically significant increases in ORR (RR = 1.454; P = 0.029), OS (HR = 0.895; P = 0.041) and TTF (HR = 0.832; P = 0.000) were found when S-1-based chemotherapy was compared to 5-fluorouracil (5-FU)-based chemotherapy. The incidence of leukopenia (RR = 0.584; P = 0.002) and stomatitis (RR = 0.230; P = 0.032) was higher in the 5-FU-based arm. S-1-based regimens had no advantage in ORR, OS, PFS, TTF and grade 3 or 4 adverse events over capecitabine-based regimens.
CONCLUSION: S-1-based chemotherapy may be a good choice for AGC because of longer survival times, better tolerance and more convenient use.
Collapse
|
|
7
|
Oki E, Emi Y, Kusumoto T, Sakaguchi Y, Yamamoto M, Sadanaga N, Shimokawa M, Yamanaka T, Saeki H, Morita M, Takahashi I, Hirabayashi N, Sakai K, Orita H, Aishima S, Kakeji Y, Yamaguchi K, Yoshida K, Baba H, Maehara Y. Phase II study of docetaxel and S-1 (DS) as neoadjuvant chemotherapy for clinical stage III resectable gastric cancer. Ann Surg Oncol 2014; 21:2340-6. [PMID: 24604583 DOI: 10.1245/s10434-014-3594-9] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Indexed: 12/14/2022]
Abstract
BACKGROUND We conducted a phase II trial to evaluate the efficacy and safety of preoperative chemotherapy with docetaxel (DTX) plus S-1 for resectable advanced gastric cancer. PATIENTS AND METHODS A total of 47 patients from 14 centers were centrally registered. Patients received DTX (35 mg/m(2)) on days 1 and 15, and daily oral administration of S-1 (80 mg/m(2)/day) for days 1-14 every 4 weeks for two courses, followed by gastrectomy with D2 lymphadenectomy. The primary endpoint was pathological response rate (pRR). This study was registered in the UMIN clinical trial registry (UMIN000000875). RESULTS The primary endpoint pRR was 47 % (90 % confidence interval (CI), 34-60 %; p < 0.0001). The response rate to preoperative chemotherapy using Response Evaluation Criteria in Solid Tumors (RECIST) was 34 %. Forty-six patients (98 %) underwent surgery, and curative resection was performed in 44 patients. Thirty-seven patients completed the protocol treatment. The most common toxicities of neoadjuvant chemotherapy were grade 3/4 neutropenia (42 %), febrile neutropenia (4 %), grade 2 anorexia (21 %), and fatigue (15 %). Treatment-related death and operative mortality was not observed in this study. CONCLUSIONS The combination of docetaxel and S-1 was well tolerated. This is promising as a preoperative chemotherapy regimen for patients with potentially resectable advanced gastric cancer.
Collapse
Affiliation(s)
- Eiji Oki
- Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan,
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
8
|
He MM, Wu WJ, Wang F, Wang ZQ, Zhang DS, Luo HY, Qiu MZ, Wang FH, Ren C, Zeng ZL, Xu RH. S-1-based chemotherapy versus capecitabine-based chemotherapy as first-line treatment for advanced gastric carcinoma: a meta-analysis. PLoS One 2013; 8:e82798. [PMID: 24349363 PMCID: PMC3861463 DOI: 10.1371/journal.pone.0082798] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2013] [Accepted: 10/28/2013] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Although both oral fluoropyrimidines were reported effective and safe, doubts exist about whether S-1 or capecitabine is more advantageous in advanced gastric carcinoma (AGC). Herein, we performed a meta-analysis to comprehensively compare the efficacy and safety of S-1-based chemotherapy versus capecitabine-based chemotherapy as first-line treatment for AGC. METHODS PubMed/Medline, EmBase, Cochrane library, and China National Knowledge Infrastructure databases were searched for articles comparing S-1-based chemotherapy to capecitabine-based chemotherapy for AGC. Primary outcomes were overall response rate (ORR), time to progression (TTP), overall survival (OS), progression-free probability, and survival probability. Secondary outcomes were toxicities. Fixed-effects model were used and all the results were confirmed by random-effects model. RESULTS Five randomized controlled trials and five cohort studies with 821 patients were included. We found equivalent ORR (38.3% vs. 39.1%, odds ratio [OR] 0.92, 95% confidence interval [CI] 0.69-1.24, P = 0.59), TTP (harzad ratio [HR] 0.98, 95% CI 0.82-1.16, P = 0.79), OS (HR 0.99, 95% CI 0.87-1.13, P = 0.91), progression-free probability (3-month OR 1.02, 95% CI 0.62-1.68, P = 0.94; 6-month OR 1.34, 95% CI 0.88-2.04, P = 0.18) and survival probability (0.5-year OR 0.90, 95% CI 0.61-1.31, P =0.57; 1-year OR 0.97, 95% CI 0.70- 1.33, P = 0.84; 2-year OR 1.15, 95% CI 0.61-2.17, P = 0.66). Equivalent grade 3 to 4 hematological and non-hematological toxicities were found except hand-foot syndrome was less prominent in S-1-based chemotherapy (0.3% vs. 5.9%, OR 0.19, 95% CI 0.06-0.56, P = 0.003). There're no significant heterogeneity and publication bias. Cumulative analysis found stable time-dependent trend. Consistent results stratified by study design, age, regimen, cycle, country were observed. CONCLUSION S-1-based chemotherapy was associated with non-inferior antitumor efficacy and better safety profile, compared with capecitabine-based therapy. We recommended S-1 and capecitabine can be used interchangeably for AGC, at least in Asia.
Collapse
Affiliation(s)
- Ming-ming He
- Department of Medical Oncology and State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Wen-jing Wu
- Department of Medical Oncology and State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Feng Wang
- Department of Medical Oncology and State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Zhi-qiang Wang
- Department of Medical Oncology and State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Dong-sheng Zhang
- Department of Medical Oncology and State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Hui-yan Luo
- Department of Medical Oncology and State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Miao-zhen Qiu
- Department of Medical Oncology and State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Feng-hua Wang
- Department of Medical Oncology and State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Chao Ren
- Department of Medical Oncology and State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Zhao-lei Zeng
- Department of Medical Oncology and State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Rui-hua Xu
- Department of Medical Oncology and State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| |
Collapse
|
|
9
|
Preoperative S-1 and docetaxel combination chemotherapy in patients with locally advanced gastric cancer. Cancer Chemother Pharmacol 2013; 73:281-5. [PMID: 24253176 DOI: 10.1007/s00280-013-2350-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2013] [Accepted: 11/04/2013] [Indexed: 12/16/2022]
Abstract
PURPOSE The combination of docetaxel and S-1 (DS) therapy is effective in patients with unresectable gastric cancer and is expected to be a regimen in neoadjuvant setting for advanced gastric cancer. This study was held to evaluate the efficacy and safety of DS followed by surgery. METHODS Patients with resectable gastric cancer received 2 courses of docetaxel 40 mg/m(2) on days 1, 15 and S-1 40 mg/m(2) bid orally on days 1-7, 15-21 every 4 weeks, followed by standard radical gastrectomy. Primary end point was the pathological response rate: rate of tumors in which one-third or more parts were affected. RESULTS Fourteen patients were enrolled. Thirteen (92.8 %) patients completed two courses of chemotherapy. Grade 3 adverse events were neutropenia in 3 (21.4 %) patients, anemia in 1 (6.2 %) patient and diarrhea in 1 (6.2 %) patient. There were no grade 4 adverse event and febrile neutropenia. All patients underwent R0 resection, and pathological response was found in 50.0 % of patients. There were no major surgical complications and no treatment-related mortality. CONCLUSIONS The neoadjuvant chemotherapy with DS was effective for patients with locally advanced gastric cancer with manageable toxicities. Further study to confirm the usefulness of this regimen is needed.
Collapse
|
|
10
|
Yang J, Zhou Y, Chen JF. Role of S-1 in treatment of advanced gastric cancer. Shijie Huaren Xiaohua Zazhi 2013; 21:2950-2956. [DOI: 10.11569/wcjd.v21.i28.2950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer is the fourth most common malignancy worldwide. More than 50% of gastric cancer patients have unresectable disease at diagnosis, and there is a high rate of local or distant recurrence, even in patients with an operable tumor. Chemotherapy is regarded as a significant and basic treatment that can provide a longer symptom-free period and improve quality of life. S-1 is a novel oral derivative of 5-FU. Compared with 5-FU, S-1 is more tolerable and effective, and will be more convenient to use for patients with advanced gastric cancer. Recent phase II randomized trials of S-1 based chemotherapy have achieved encouraging results with regard to objective response rate and overall survival. This paper aims to review the efficacy of S-1 in treating advanced gastric cancer, molecular markers that can predict efficacy, and the prospect for therapy with S-1 in combination with new chemotherapeutic drugs or molecularly targeted drugs.
Collapse
|
|
11
|
Shigeyasu K, Kagawa S, Uno F, Nishizaki M, Kishimoto H, Gochi A, Kimura T, Takahata T, Nonaka Y, Ninomiya M, Fujiwara T. Multicenter phase II study of S-1 and docetaxel combination chemotherapy for advanced or recurrent gastric cancer patients with peritoneal dissemination. Cancer Chemother Pharmacol 2013; 71:937-43. [PMID: 23355040 DOI: 10.1007/s00280-013-2086-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2012] [Accepted: 01/10/2013] [Indexed: 12/15/2022]
|
|
12
|
Kunisaki C, Ono HA, Hasegawa S, Oshima T, Fujii S, Tokuhisa M, Izumisawa Y, Takagawa R, Kimura J, Kosaka T, Makino H, Akiyama H, Endo I. Low-dose docetaxel and cisplatin combination chemotherapy for stage II/III gastric cancer showing resistance to S-1 adjuvant chemotherapy: a phase I study. J Chemother 2012; 24:364-8. [PMID: 23174102 DOI: 10.1179/1973947812y.0000000042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
To establish a safe, long-term regimen of docetaxel (DOC) and cisplatin (CDDP) in an outpatient setting for gastric cancer refractory to S-1 adjuvant chemotherapy, a dose-escalating phase I study was conducted. Cohorts of patients were treated with escalating doses of DOC (starting at 20 mg/m² per week with 5 mg/m² increments) and a fixed dose of CDDP (25 mg/m²). Drugs were administered on days 1, 8, and 15. A cycle of this treatment was 28 days. In total, 52 courses were performed, and the mean number of courses was 5.3. Two of the four patients at dose level 3 showed dose-limiting toxicities (grade 4 neutropenia, and grade 3 anorexia and dehydration). The recommended dose (RD) of DOC was therefore defined as 25 mg/m². There is a need for a phase II clinical trial using this regimen in patients with S-1-refractory stage II/III gastric cancer.
Collapse
Affiliation(s)
- Chikara Kunisaki
- Department of Surgery, Gastroenterological Center, Yokohama City University, Yokohama, Japan.
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
13
|
Kunisaki C, Takahashi M, Ono HA, Oshima T, Takagawa R, Kimura J, Kosaka T, Makino H, Akiyama H, Endo I. Inflammation-based prognostic score predicts survival in patients with advanced gastric cancer receiving biweekly docetaxel and s-1 combination chemotherapy. Oncology 2012; 83:183-91. [PMID: 22890015 DOI: 10.1159/000341346] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2012] [Accepted: 06/18/2012] [Indexed: 01/28/2023]
Abstract
OBJECTIVES This study was conducted to determine the prognostic value of the Glasgow Prognostic Score (GPS), an inflammation-based prognostic score composed of C-reactive protein and albumin, for patients with advanced cancer. METHODS A total of 83 advanced gastric cancer patients receiving biweekly docetaxel/S-1 treatment (DS) were included in the study. To identify the value of GPS as prognostic factor for disease-specific survival (DSS) and progression-free survival (PFS), univariate and multivariate analyses were performed. RESULTS Unresectable tumors were observed in 78 patients and recurrent tumors were detected in 5 patients. Of these, 12 patients underwent gastrectomy. There were significant correlations between the GPS and the neutrophil/lymphocyte ratio. Univariate analysis revealed that the GPS, Eastern Cooperative Oncology Group performance status and gastrectomy after DS treatment significantly affected prognosis. Multivariate analysis showed that the GPS, age and gastrectomy independently influenced DSS, and that the GPS and gastrectomy also influenced PFS. Multivariate analysis restricted to patients without gastrectomy showed that the GPS and age independently affected DSS, and that the GPS influenced PFS. CONCLUSION In the low GPS group, it may be possible to obtain favorable outcomes by chemotherapy in advanced gastric cancer patients. However, a well-designed prospective trial in a large patient cohort is required to corroborate the prognostic value of the GPS.
Collapse
Affiliation(s)
- Chikara Kunisaki
- Department of Surgery, Gastroenterological Center, Yokohama City University, Japan.
| | | | | | | | | | | | | | | | | | | |
Collapse
|