Treatment outcome and safety of docetaxel as the third-line chemotherapy in advanced gastric cancer after progression or after failure of FOLFOX and FOLFIRI-based sequential chemotherapy.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 133-133
Author(s):  
I. Hwang ◽  
J. Kang ◽  
B. Park ◽  
S. Park ◽  
M. Jang ◽  
...  

133 Background: We performed multicenter retrospective study to evaluate the activity and the safety of a docetaxel as the third-line chemotherapy in advanced gastric cancer (AGC) patients who had undergone oxaliplatin (FOLFOX) and irinotecan (FOLFIRI)-based chemotherapy regimens. Methods: Thirty-eight patients with AGC previously treated were eligible for this study. Patients received docetaxel 30 mg/m2 +/- cisplatin 30 mg/m2 IV on day 1, 8 or docetaxel 60 mg/m2 +/- cisplatin 60 mg/m2 IV on day 1 every 3 weeks until disease progression, and responses were assessed after every two cycles according to RECIST criteria and toxicity was evaluated by NCI-CTC. Results: Thirty-two out of 38 patients were evaluable for response. A total of 95.1 cycles of chemotherapy (median 2, range 0.5–7) were administered. Relative dose intensities of docetaxel and cisplatin were 93.4% and 87.8%, respectively. The overall response rate was 15.6% and the disease control rate was 50%. With a median follow-up duration of 3.1 months (range 0.3-14.3 months), 36 patients had disease progression, and 34 patients had died at the time of analysis. The median progression-free survival was 1.8 months (95% CI, 1.3–2.3 months). The median overall survival was 3.1 months (95% CI, 2.3–3.9 months). Grade 3 or 4 hematologic toxicities included neutropenia in thirteen patients (38.3%), febrile neutropenia in four patients (11.7%). and thrombocytopenia in one patient (2.9%). Other grade 3 or 4 toxicities included neuropathy in three patients (8.8%) and mucositis in two patients (5.9%). There were three treatment-related deaths (8.8%) caused by infection associated with neutropenia. Conclusions: Salvage docetaxel chemotherapy in AGC patients failed in oxaliplatin and irinotecan-based treatment is not recommend routinely. However, selected patients with good performance status and sufficient albumin levels may have derived some survival benefits from salvage chemotherapy. No significant financial relationships to disclose.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 83-83
Author(s):  
Yasunobu Ishizuka ◽  
Tetsuji Terazawa ◽  
Hiroki Yukami ◽  
Toshifumi Yamaguchi ◽  
Shin Kuwakado ◽  
...  

83 Background: As a result of ATTRACTION2, nivolumab was added to the third line treatment in advanced gastric cancer (AGC), but the response rate was about 10%. As there is no predictive biomarker and no comparison with cytotoxic regimen, it is difficult to choice the regimen. Therefore, we examined the treatment outcome of cytotoxic regimen in third line treatment in the real world retrospectively. Methods: We retrospectively evaluated efficacy and safety of cytotoxic regimen as third-line treatment in patients with AGC between July 2015 and December 2017. Results: Among 138 patients received chemotherapy as first line, 29 patients (21%) received third line therapy. The characteristics were as follows; the median age, 70 years old (range 34-80); male/female, 19 (66%)/10 (34%); performance status (PS) 0/1/2, 7/18/4. The overall response rate was 19% and the disease control rate was 38%. The median overall survival (OS) was 6.6 months and the progression free survival was 3.8 months. The most common grade 3/4 hematological toxicities were neutropenia (27%), followed by anemia (27%) and febrile neutropenia (13.7%). Grade 3/4 nonhematological toxicities included anorexia (27.6%), diarrhea (10%), nausea (10%). Conclusions: Cytotoxic regimen as third line showed acceptable activity, but only 21% of patients could received the third line chemotherapy. The further investigation of predictive biomarker of nivolumab is expected.


2019 ◽  
Vol 12 (2) ◽  
pp. 523-528
Author(s):  
Hirofumi Tazawa ◽  
Takahisa Suzuki ◽  
Toshiaki Komo ◽  
Haruna Kubota ◽  
Shunya Tahara ◽  
...  

Peritoneal metastasis (PM) is detected in 14% of gastric cancers at the time of initial diagnosis, with a median survival time of 4 months. A 66-year-old woman diagnosed with cT4a(SE) N2M1(LYN) cStage IV was treated with three lines of chemotherapy for a year. During the third line of chemotherapy, computed tomography (CT) scan revealed a large amount of ascites, periportal collar sign, and bilateral ureteral stenosis owing to PM. The tumor biomarkers (CEA and CA 19–9) remained elevated similar to the initial levels. The patient was administered 3 mg/kg nivolumab intravenously biweekly as the fourth line of chemotherapy. Three months after the nivolumab treatment, gastroscopy revealed an extreme reduction of the tumor size, while CT scan revealed the absence of ascites and a well-controlled tumor. There was no immune-related adverse event with nivolumab during and after the treatment, and performance status improved to 0. The patient has been alive for about 2.5 years since her first visit with her sixth line of chemotherapy (docetaxel). We report a case of advanced gastric cancer with PM that was treated successfully with nivolumab.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15671-e15671
Author(s):  
J. Lim ◽  
J. Kim ◽  
H. Yi ◽  
H. Kim ◽  
M. Lee ◽  
...  

e15671 Background: Elderly patients have often been excluded from clinical trials and only limited data are available regarding treatment of these patients. The efficacy of S-1 chemotherapy for elderly patients with advanced gastric cancer (AGC) is not well investigated. The aim of this study is to evaluate the efficacy and safety of S-1 monotherapy in elderly patients with AGC to whom conventional chemotherapy is difficult to deliver. Methods: From January 1, 2007 to August 31, 2008, a total of seventeen patients older than 70 were given S1 monotherapy. They received S-1 at a dose of 40mg/m2 BID either every 3 weeks (2 weeks on, 1 week off) or every 6 weeks (4 weeks on, 2 weeks off). Response was assessed according to RECIST criteria. Results: The patients consisted of 11 men and 6 women whose median age was 77 years (range: 71–83) with their performance status in 1 to 2. Five patients had recurrent AGC and the other 12 patients metastatic AGC at the time of diagnosis. Total 89 cycles of S-1 chemotherapy were given (median 4 cycles, range 2–12). Fifteen patients were evaluable for response because of early death in 2 patients. Response rate was 17.6% (95% Condifence Interval, 0 to 35.7); Complete remission in 0, partial remission in 3 (17.6%) and stable disease in 5 patients (29.4%). At a median follow up of 9.7 months (range: 8–11.4), median progression free survival was 5.1 months (range: 3.5–6.7) and overall survival was 9.5 months (range: 5.6–15.5). Most of the adverse effects of S1 monotherapy did not extend beyond grade 3. Grade 3 or 4 non- hematologic toxicities were not frequent and were easily manageable except in two, one of whom died of neutropenic sepsis and the other who died of subdural hemorrhage in grade 4 thrombocytopenia. Conclusions: S1 chemotherapy showed modest efficacy in elderly patients with AGC. The hematologic toxicity should be cautiously monitored in these elderly patients to avoid fatal events. Further studies are warranted for optimal management of elderly patients with metastatic or recurrent AGC. No significant financial relationships to disclose.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4551-4551
Author(s):  
S. Cho ◽  
S. Lee ◽  
J. Hwang ◽  
W. Bae ◽  
H. Shim ◽  
...  

4551 Background: S-1 is a fourth-generation oral fluoropyrimidine that was developed to mimic protracted continuous infusion of 5-fluorouracil (5-FU). In previous study, S-1 demonstrated promising activity which is comparable to combination chemotherapy in advanced gastric cancer. This phase II study evaluated the efficacy and safety of S-1 salvage chemotherapy, in patients with taxane and cisplatin refractory gastric cancer. The primary end point was progression free survival and secondary end points were overall survival, safety and clinical benefit. Methods: Patients were eligible if they had histologically documented gastric adenocarcinoma previously treated with taxane (docetaxel or paclitaxel) and cisplatin; age≥18; Eastern Clinical Oncology Group (ECOG) performance status of 2 or less; adequate organ function; no evidence of gastrointestinal obstruction or passage disturbance. S-1 treatment was performed according to BSA as followed; < BSA 1.25, 80 mg/day, 1.25 ≤ BSA < 1.5, 100 mg/day; BSA ≥ 1.5, 120 mg/day. Every dosage was delivered divided two times and administered for 4 weeks followed by 2 weeks of resting period. Treatment continued until progression of disease or life-threatening adverse events were occurred. Results: Fifty-four patients were enrolled in this study and of the patients, forty-eight patients were evaluable. A total 194 chemotherapy cycles were administered and median number of cycles was three. Four (8.3%) patients had a partial response and 18 (37.5%) patients had stable disease. The median progression free survival and overall survival were 3.8 and 10.2 months, respectively. Grade III/IV hematologic toxicities included neutropenia in 6 patients (12.5%) and there was no febrile neutropenia. Most of nonhematologic toxicities were diarrhea, asthenia, and mucositis, and there was no grade 3 or grade 4 except two patients, who developed grade 3 anorexia and diarrhea, respectively. The clinical benefit response was observed in 16 patients (33.3%). Conclusions: This results showed that S-1 monotherapy was active and safe salvage chemotherapy in patients with advanced gastric cancer previously treated with taxane and cisplatin. No significant financial relationships to disclose.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 113-113
Author(s):  
Takeshi Kawakami ◽  
Nozomu Machida ◽  
Masahiro Kawahira ◽  
Sadayuki Kawai ◽  
Yosuke Kito ◽  
...  

113 Background: Several randomized trials demonstrated the survival benefit in advanced gastric cancer patients (AGC pts) receiving irinotecan or taxanes as second-line chemotherapy (SLC). Taxanes are used for SLC in daily clinical practice in Japan because of its less toxicity, especially in AGC pts with peritoneal dissemination, compared with irinotecan. Although irinotecan is often administered after refractory or intolerant to taxanes as SLC, the efficacy and safety of irinotecan as third-line chemotherapy (TLC) is still unclear. Methods: We retrospectively investigated the data of AGC pts administered irinotecan 150mg/m2 as TLC every two weeks until disease progression, unacceptable toxicity, or pts’ refusal between December 2002 and June 2015. Inclusion criteria were (1) age 75 years or less (2) refractory or intolerant to fluoropyrimidine with or without platinum as first-line chemotherapy (3) refractory or intolerant to taxanes as SLC. Results: A total of 52 pts were analyzed. Pts’ characteristics were as follows: median age, 66 (range, 33-75) years; male/female, 35/17 pts; ECOG PS 0-1/2, 42/10 pts; peritoneal dissemination +/-, 32/20 pts; ascites +/-, 22/30 pts, number of metastatic sites 1-2/3-4, 44/8 pts. Median follow-up period was 548 (141-1931) days. Median progression-free survival was 70 days (95%CI 49-137) and median overall survival was 144 days (95%CI 120-231) from the initiation of irinotecan administration. Response rate and disease control rate was 10.8% and 50.4%, respectively. Relative dose intensity was 74.7% (56 mg/m2/week); 14 pts needed dose reduction in the first course, and 22 pts after the second course. Grade 3 or 4 neutropenia, anemia, diarrhea, nausea, and febrile neutropenia were observed in 13 (25%), 21 (40.4%), 5 (9.6%), 3 (5.8%) and 3 (5.8%) pts, respectively. No treatment-related death was observed. Conclusions: This study suggests that irinotecan monotherapy as TLC has acceptable anti-tumor effect and has manageable toxicity in appropriately selected AGC pts.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 382-382
Author(s):  
Hisateru Yasui ◽  
Akihito Kawazoe ◽  
Kensei Yamaguchi ◽  
Yuji Negoro ◽  
Mizutomo Azuma ◽  
...  

382 Background: The KEYNOTE-059 study showed the preliminary antitumor activity and tolerability of chemotherapy with pembrolizumab (P) for advanced gastric cancer (AGC). In Japan, S-1 + platinum regimen is a standard chemotherapy for AGC. The KEYNOTE-659 study (NCT03382600) investigated the efficacy and safety of S-1 + oxaliplatin (SOX; cohort 1) or cisplatin (SP; cohort 2) with P as the first line treatment in patients (pts) with human epidermal growth factor receptor 2 (HER2)-negative, programmed death-ligand 1 (PD-L1)-positive AGC. Here, we report the results of cohort 1. Methods: The key inclusion criteria were as follows: age ≥18 to ≤75 years; an ECOG performance status of 0 or 1; and chemotherapy-naïve, HER2-negative and PD-L1-positive AGC. PD-L1 positivity was defined as a combined positive score of ≥1 using the IHC 22C3 PharmDx assay. An S-1 dose of 40-60 mg per dose was orally administered, twice daily, for the first 2 weeks of a 3-week cycle. P (200 mg) and oxaliplatin (OX; 130 mg/m2) were administered on day 1 of each cycle. The primary endpoint was overall response rate (ORR) that was assessed by a blinded independent central review (BICR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DOR), and safety. Results: From April to September 2018, 54 pts were enrolled at 25 sites in Japan. The median follow-up time was 10.1 months. The median number of P doses and cycles in SOX were 9 (range, 2-18) and 6 (range, 2-13), respectively. The relative dose intensities of S-1 and OX were 73% and 60%, respectively. The ORR and DCR assessed by BICR were 72.2% (95% CI 58.4-83.5) and 96.3% (95% CI 87.3-99.5), respectively. The median PFS was 9.4 months (95% CI 6.6-NR). Median DOR and OS were not reached. Grade ≥3 adverse events (AEs) were reported in 31 pts (57.4%). The most common treatment-related AEs of grade ≥3 were thrombocytopenia (14.8%), neutropenia (13.0%), colitis (7.4%), and adrenal insufficiency (5.6%). There were no treatment-related deaths. Conclusions: This study showed the encouraging efficacy and manageable safety of SOX with P therapy as a first line in pts with HER2-negative, PD-L1-positive AGC. Clinical trial information: NCT03382600.


2020 ◽  
Vol 12 ◽  
pp. 175883592094237
Author(s):  
Takahiro Ishii ◽  
Akihito Kawazoe ◽  
Akinori Sasaki ◽  
Saori Mishima ◽  
Sawada Kentaro ◽  
...  

Background: The use of nivolumab or irinotecan as the third-line treatment for patients with advanced gastric cancer (AGC) remains controversial. Methods: This study analyzed patients with AGC treated with nivolumab or irinotecan (nivolumab group or irinotecan group, respectively) from May 2016 to April 2019 following two or more previous lines of chemotherapy. Univariate survival analysis was conducted to identify the clinical and molecular factors associated with progression-free survival (PFS). Results: A total of 156 patients (74 treated with nivolumab and 82 treated with irinotecan) were analyzed. The median PFS was 1.9 months in both treatment groups. The median overall survival (OS) was 7.2 and 6.2 months in the nivolumab and irinotecan groups, respectively. Eastern Cooperative Oncology Group performance status of 1 or more, liver metastasis, a large tumor size at baseline, and HER2-positive status were associated with a worse PFS in the nivolumab group compared with the irinotecan group. The nivolumab group showed a significantly longer PFS (median 3.1 versus 2.0 months) and OS (median 12.9 versus 7.8 months) than the irinotecan group in patients with 0 or 1 of these factors, whereas the irinotecan group showed a significantly longer PFS (median 1.0 versus 1.8 months) and a trend of longer OS (median 3.9 versus 6.1 months) in patients with ⩾2 of these factors. Conclusions: Some clinical and molecular factors were associated with outcomes following nivolumab or irinotecan as the third- or later-line treatment in patients with AGC. These factors must be considered while selecting an optimal treatment option.


2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Kohei Ogawa ◽  
Ayumu Hosokawa ◽  
Akira Ueda ◽  
Seiko Saito ◽  
Hiroshi Mihara ◽  
...  

Background. S-1 plus cisplatin has been established to be standard first-line chemotherapy for advanced gastric cancer in Japan. The optimal second-line treatment refractory to S-1 plus cisplatin remains unclear.Methods. We retrospectively studied the efficacy, toxicity, and survival of irinotecan plus mitomycin C in patients with advanced gastric cancer refractory to a fluoropyrimidine plus cisplatin.Results. Twenty-four patients were studied. Prior chemotherapy was S-1 plus cisplatin in 15 patients, S-1 plus cisplatin and docetaxel in 8, and 5-fluorouracil plus cisplatin with radiotherapy in 1. The overall response rate was 17.4%. The median overall survival was 8.6 months, and the median progression-free survival was 3.6 months. Grade 3 or 4 toxicities included leukopenia (33%), neutropenia (50%), anemia (33%), thrombocytopenia (4%), anorexia (13%), diarrhea (4%), and febrile neutropenia (13%).Conclusion. A combination of irinotecan and mitomycin C is potentially effective in patients with advanced gastric cancer refractory to a fluoropyrimidine plus cisplatin.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15170-15170
Author(s):  
C. Herrmann ◽  
D. Jaeger ◽  
T. Herrmann

15170 Background: The role of second-line chemotherapy in advanced gastric cancer is not yet established. We analyzed patients with advanced gastric cancer treated at our department between 2002 and 2005 comparing the outcome of patients with first-line chemotherapy only and those who received second-line chemotherapy. Patients and Methods: 51 patients with metastatic or recurrent histologically confirmed gastric cancer were analyzed in this retrospective study. The choice of chemotherapy depended on the attending physician. Results: Altogether, 17 patients (33.3 %) were treated with only one chemotherapy regimen, whereas 34 patients (66.6 %) received at least two different chemotherapy regimens. During the last years, the preference for certain chemotherapy regimens changed. At the time of analysis, 9 patients were still alive. Median overall survival was 11 months (range: 1–41). Patients who received only one chemotherapy regimen were older (median age 70, range: 47–81), had a shorter TTP (3.5 months, range: 1–15) and a shorter overall survival (6 months, range: 2–25) than patients receiving sequential chemotherapies (median age 61.5 (range: 33–79) p = 0,009, TTP under first-line therapy 5 months (1–17), p = 0,45, overall survival 14.5 months (2–41), p = 0,001). Response to second-line chemotherapy was assessed in 32 patients: Partial remission was detected in 4 patients (12.5 %), stable disease for = 3 months in 15 patients (46.8 %), whereas disease progression occurred in 12 patients (37.5 %). 10 of 51 patients (19.6 %) received more than two different treatments: 4 patients had third-line chemotherapy, 6 patients had more than 3 different therapies. Overall survival was 13 months (11–22) for patients with third-line chemotherapy and 29 months (16–41) for patients receiving more than three different treatment regimens. Conclusion: Although a number of active antineoplastic drugs are available for the treatment of advanced gastric cancer, the prognosis is still poor. Selected patients may benefit from salvage chemotherapy after failure of first-line chemotherapy. No significant financial relationships to disclose.


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