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1.
Takashi Nishimura Satoru Iwasa Kengo Nagashima Natsuko Okita Atsuo Takashima Yoshitaka Honma Ken Kato Tetsuya Hamaguchi Yasuhide Yamada Yasuhiro Shimada Narikazu Boku 《Gastric cancer》2017,20(4):655-662
Background
Because standard chemotherapy for advanced gastric cancer consists of oral fluoropyrimidines plus platinum as first-line therapy, with paclitaxel plus ramucirumab as the second line, irinotecan is usually positioned as third-line chemotherapy in clinical practice in Japan.Methods
A retrospective evaluation was conducted to determine the efficacy and safety of irinotecan as third-line chemotherapy for advanced gastric cancer in patients refractory or intolerant to fluoropyrimidines, platinum, and taxanes.Results
Between February 2008 and December 2013, 52 patients received third-line irinotecan monotherapy. Among the 32 patients with measurable lesions, 1 patient achieved a confirmed partial response and 6 patients had stable disease. The overall response rate was 3% and the disease control rate was 22%. Median progression-free survival was 2.3 months [95% confidence interval (CI), 1.8–2.8] and median overall survival was 4.0 months (95% CI, 2.6–5.3). The most common adverse events of grade 3 severity or higher were neutropenia (27%), febrile neutropenia (12%), anorexia (12%), and diarrhea (6%). Although no treatment-related deaths occurred, 2 patients (4%) died of disease progression within 30 days after the last administration of irinotecan.Conclusion
Irinotecan monotherapy appears to be tolerated but was shown to have modest activity as third-line chemotherapy for advanced gastric cancer.2.
Sook Ryun Park Myeong-Cherl Kook Il Ju Choi Chan Gyoo Kim Jong Yeul Lee Soo-Jeong Cho Young-Woo Kim Keun Won Ryu Jun Ho Lee Jong Seok Lee Young-Iee Park Noe Kyeong Kim 《Cancer chemotherapy and pharmacology》2010,65(3):579-587
Purpose
We performed a retrospective study to evaluate the efficacy of cetuximab plus chemotherapy in metastatic gastric cancer (MGC) patients previously treated with chemotherapy and to investigate potential predictors of treatment efficacy in those patients.Methods
Thirty-two patients with MGC were included in this study. Cetuximab was delivered, often combined with irinotecan-based chemotherapy. Thirty patients were analyzed for K-ras mutations via direct sequencing of the tumor DNA.Results
Patients were heavily pretreated with a median number of three previous lines of palliative chemotherapy (56% of the patients were refractory to all of the following drugs: fluoropyrimidines, cisplatin, irinotecan, oxaliplatin, and docetaxel) and 53% of the patients displayed poor performance status. Of 28 response-assessable patients, the overall response rate to cetuximab plus chemotherapy was 3.6% [95% confidence interval (CI) 0–10.5%] and the disease control rate was 28.6%. The median progression-free survival (PFS) was 1.7 months (95% CI 1.3–2.1 months), and the median overall survival (OS) was 3.2 months (95% CI 1.4–5.0 months). Multivariate analyses revealed that skin rash and performance status were significantly associated with PFS and OS. The presence of a K-ras mutation (13.3%) was not associated with either PFS or OS.Conclusion
Our study suggests that MGC patients with good performance status and skin rash benefit most from salvage cetuximab combined with chemotherapy, even in heavily pretreated status. 相似文献3.
Yousuke Nakai Hiroyuki Isayama Takashi Sasaki Naminatsu Takahara Tsuyoshi Hamada Rie Uchino Suguru Mizuno Koji Miyabayashi Keisuke Yamamoto Dai Mohri Hirofumi Kogure Natsuyo Yamamoto Kenji Hirano Hideaki Ijichi Keisuke Tateishi Minoru Tada Kazuhiko Koike 《Cancer chemotherapy and pharmacology》2013,72(6):1291-1297
Purpose
In salvage chemotherapy for refractory pancreatic cancer, early assessment is important to avoid unnecessary toxicities from ineffective chemotherapy. Early CA19-9 change after the first course as a prognostic factor was evaluated in this setting.Methods
Patients receiving salvage chemotherapy were retrospectively studied. CA19-9 was measured prior to and after the first course. Cox regression analysis was performed for prognostic factors for progression-free survival (PFS) and overall survival (OS), using the landmark method defined as a day of CA19-9 measurement after the first course.Results
A total of 239 salvage regimens were given in 167 patients. Median PFS and OS were 2.7 and 6.1 months, respectively. Median pretreatment CA19-9 was 2,362 U/mL, and median CA19-9 change after the first course was 17.8 % increase. CA19-9 change was associated with tumor response, and PFS was 1.7 versus 3.5 months and OS was 3.9 and 8.6 months in patients with ≥50 % versus <50 % increase. In the multivariate analyses, CA19-9 increase ≥50 % was prognostic of both PFS and OS (HR 2.28 and 2.50, p < 0.001, respectively).Conclusion
CA19-9 change after the first course was prognostic of PFS and OS in refractory pancreatic cancer. Early discontinuation should be considered given the palliative setting. 相似文献4.
Eun Joo Kang Seock-Ah Im Do-Youn Oh Sae-Won Han Jin-Soo Kim In Sil Choi Jin Won Kim Yu Jung Kim Jee Hyun Kim Tae-You Kim Jong Seok Lee Yung-Jue Bang Keun-Wook Lee 《Gastric cancer》2013,16(4):581-589
Background
The aim of this study was to evaluate the activity and safety of the combination chemotherapy of 5-fluorouracil (5-FU), leucovorin, and irinotecan (FOLFIRI regimen) after failure of fluoropyrimidine, platinum, and taxane in gastric cancer (GC) and to evaluate the prognostic factors for survival.Methods
Patients received biweekly FOLFIRI chemotherapy as third-line treatment. The FOLFIRI-1 consisted of irinotecan (180 mg/m2 in a 2-h infusion) on day 1, and then leucovorin (200 mg/m2 in a 2-h infusion) and 5-FU (a 400 mg/m2 bolus, followed by 600 mg/m2 in a 22-h continuous infusion) on days 1 and 2. FOLFIRI-2 consisted of irinotecan (180 mg/m2 in a 2-h infusion) on day 1, and then leucovorin (400 mg/m2 in a 2-h infusion) and 5-FU (a 400 mg/m2 bolus, followed by 2400 mg/m2 in a 46-h continuous infusion) on day 1.Results
A total of 158 patients were included. The overall response rate was 9.6 % in patients with measurable lesions. The median progression-free survival (PFS) and overall survival (OS) were 2.1 months [95 % confidence interval (CI), 1.7–2.5] and 5.6 months (95 % CI, 4.7–6.5), respectively. The major grade 3/4 toxicity was myelosuppression (36.7 %). Good performance status (PS), fewer metastatic sites, and longer duration from the first-line to third-line chemotherapy were independent prognostic factors affecting both PFS and OS.Conclusions
The FOLFIRI regimen showed antitumor activity and tolerable toxicity profiles against advanced GC in the third-line setting. Patients with good PS, fewer metastatic sites and longer previous treatment duration might have the maximal benefit from third-line chemotherapy. 相似文献5.
Sung-Ji Lee Sang-Hee Cho Ju-Young Yoon Jun-Eul Hwang Woo-Kyun Bae Hyun-Jeong Shim Ik-Joo Chung 《Cancer chemotherapy and pharmacology》2009,65(1):159-166
Purpose
S-1 is a fourth-generation oral fluoropyrimidine that was developed to mimic the effects achieved with protracted continuous infusion of 5-fluorouracil (5-FU). This phase II study evaluated the efficacy and safety of S-1 salvage chemotherapy in patients with paclitaxel- and cisplatin-refractory gastric cancer. The primary end point was progression-free survival; secondary end points were overall survival, safety, and clinical benefit.Methods
Patients were eligible for the study if they had histologically documented gastric adenocarcinoma previously treated with paclitaxel and cisplatin, age ≥ 18 years, Eastern Clinical Oncology Group performance status ≤2, adequate organ function, and no evidence of gastrointestinal obstruction or passage disturbance. Patients were treated with a dose of S-1 based on body surface area (BSA) as follows: BSA < 1.25 m2, 80 mg/day; 1.25 ≤ BSA < 1.5 m2, 100 mg/day; BSA ≥ 1.5 m2, 120 mg/day. The total dose was divided in two and administered twice daily for 4 weeks followed by a 2-week rest period.Results
Of the 53 patients enrolled in this study, 49 were evaluable. A total of 190 chemotherapy cycles were administered, and the median number of cycles was 2. Five patients (9.4%) had a partial response, and 18 (34%) had stable disease. Median progression-free survival and overall survival were 4.9 and 10.4 months, respectively. Grade 3/4 hematological toxicities included neutropenia in six patients (11%) but no cases of febrile neutropenia were found. Most of the non-hematological toxicities were diarrhea, asthenia, and mucositis, but none reached grade 3 or grade 4 in severity. Improvement of pain was observed in 17 patients (32.1%).Conclusions
S-1 monotherapy provides active and safe salvage chemotherapy for patients with advanced gastric cancer who have been previously treated with paclitaxel and cisplatin. 相似文献6.
Kensuke Bekku Takashi Saika Yasuyuki Kobayashi Ryo Kioshimoto Taiki Kanbara Yasutomo Nasu Hiromi Kumon 《International journal of clinical oncology / Japan Society of Clinical Oncology》2013,18(1):110-115
Background
The clinical impact of salvage surgery after chemotherapy on cancer survival of patients with metastatic urothelial carcinoma is controversial. We aimed to verify the clinical role of salvage surgery by analyzing the long-term outcome in patients with urothelial carcinoma treated by chemotherapy.Methods
Between 2003 and 2010 at a single institution, 31 of 47 patients (66%) with metastatic urothelial carcinoma showed objective responses (CR in 4, PR in 27) after multiple courses of cisplatin/gemcitabine/paclitaxel-based chemotherapy, and a cohort of patients with partial response (PR) were retrospectively enrolled. Twelve (10 male and 2 female, median age 64.0 years) of 27 patients with PR underwent salvage surgeries after the chemotherapy: metastatectomy of residual lesions (10 retroperitoneal lymph nodes, 2 lung), and 6 radical surgeries for primary lesions as well. Progression-free survival and overall patient survival rates were analyzed retrospectively and compared with those of patients without salvage surgery.Results
All 12 patients achieved surgical CR. Pathological findings of metastatic lesions showed viable cancer cells in 3 patients. In univariate analysis, sole salvage surgery affected overall survival in 27 patients with PR to the chemotherapy (P = 0.0037). Progression-free survival and overall survival rates in patients with salvage surgery were better than those in 15 PR patients without the surgery (39.8 vs. 0%, and 71.6 vs. 12.1% at 3 years, P = 0.01032 and 0.01048; log-rank test).Conclusions
Salvage surgery for patients with residual tumor who achieve partial response to chemotherapy could have a possible impact on cancer survival. 相似文献7.
Keun-Wook Lee Yu Jung Kim Kyung-Hun Lee Sae-Won Han Tae-Yong Kim Do-Youn Oh Seock-Ah Im Tae-You Kim Yung-Jue Bang In Sil Choi Jee Hyun Kim 《Cancer chemotherapy and pharmacology》2014,74(3):447-455
Purpose
To investigate the efficacy of gemcitabine plus uracil–tegafur (UFT) combination chemotherapy as a salvage treatment in patients with metastatic colorectal cancer (MCRC).Methods
This single-arm phase II study was conducted at three institutions in Korea. Patients with MCRC refractory to fluoropyrimidine, oxaliplatin and irinotecan were enrolled. Gemcitabine 800 mg/m2 was administered intravenously on days 1, 8 and 15. UFT 200 mg/m2/day was taken orally in three divided doses on days 1–21. Cycles were repeated every 4 weeks, and tumor evaluation was carried out every 8 weeks. The primary endpoint of this study was 8-week progression-free survival (PFS) rate.Results
Forty-one patients were enrolled. Fourteen patients received gemcitabine/UFT as a third-line treatment and 37 patients as a fourth-line or later-line therapy. Toxicities were easily manageable, and non-hematologic toxicities of ≥grade 3 were rare. The most common toxicity of ≥grade 3 was neutropenia (20.0 %). One patient showed partial response (response rate, 2.4 %) and 14 (34.1 %) showed stable disease. The 8-week PFS rate was 42.3 %. The median PFS was 1.7 months [95 % confidence interval (CI) 1.6–1.8 months], and the median overall survival was 9.2 months (95 % CI 5.8–12.6 months).Conclusions
Overall efficacy of gemcitabine/UFT in refractory MCRC was unsatisfactory. However, we could find a minor proportion of patients who showed prolonged tumor stabilization to gemcitabine/UFT. Further studies are warranted to identify a patient subgroup that might have benefits from gemcitabine/UFT therapy. 相似文献8.
Kohei Nakachi Junji Furuse Taira Kinoshita Mitsuhiko Kawashima Hiroshi Ishii Masafumi Ikeda Shuichi Mitsunaga Satoshi Shimizu 《Cancer chemotherapy and pharmacology》2010,66(3):527-534
Purpose
The aim of this study was to investigate the feasibility and efficacy of induction chemotherapy with gemcitabine and S-1 followed by chemoradiotherapy for locally advanced pancreatic cancer.Methods
Patients with locally advanced unresectable pancreatic cancer received four cycles of induction chemotherapy consisting of 30-min intravenous infusions of gemcitabine 1,000 mg/m2 on days 1 and 8 and oral S-1 40 mg/m2 twice daily on days 1–14 of a 21-day cycle. Those without disease progression received chemoradiotherapy of 30 Gy in ten fractions with 250 mg/m2 of gemcitabine on days 1 and 8.Results
A total of 20 patients were treated. Median follow-up time was 431 days (range 133–1,014 days). Four cycles of induction chemotherapy were completed in 18 patients, and 16 patients received chemoradiotherapy, which was completed without delay in all. Grade 3–4 toxicities associated with induction chemotherapy were neutropenia (50%); anemia (20%); thrombocytopenia (10%); febrile neutropenia (5%); nausea (10%); anorexia (10%); and vomiting, fatigue, dehydration, stomatitis, and rash (5%). Grade 3–4 toxicities among those receiving chemoradiotherapy were neutropenia (13%) and anemia (6%). Median progression-free survival was 8.1 months. Median overall survival was 14.4 months, with a 1-year survival rate of 54.2%.Conclusions
The regimen of induction chemotherapy with gemcitabine and S-1 followed by chemoradiotherapy used in the present study demonstrated promising activity in locally advanced pancreatic cancer. Further consideration of radiation schedule and duration of induction chemotherapy is required to enhance the efficacy of this strategy. 相似文献9.
Oscar Arrieta Luis-Alberto Medina Enrique Estrada-Lobato Laura-Alejandra Ramírez-Tirado Víctor-Osvaldo Mendoza-García Jaime de la Garza-Salazar 《Cancer chemotherapy and pharmacology》2014,74(1):211-215
Background
There are currently no available biomarkers for advanced pleural mesothelioma that determine which patients could benefit from a specific chemotherapy regimen.Methods
Based on the results of a previously published phase II study, we associated the 99mTechnetium-labelled liposomal doxorubicin (99mTc-LD) uptake value (75 % cut-off) with the response rate, progression-free survival and overall survival of patients treated with a combination of liposomal doxorubicin and cisplatin.Results
Patients with tumours exhibiting increased 99mTc-LD uptake showed better response rates, progression-free survival and overall survival than those exhibiting lower uptake 73.3 versus 15 % (p < 0.001); 6.9 versus 3.2 months (p = 0.033) and 23 versus 6.6 months (p = 0.001), respectively.Conclusion
99mTc-DL uptake in tumour tissue could define a set of patients who would benefit from this chemotherapy regimen. 相似文献10.
Naohiro Watanabe Hiroyuki Taniguchi Yasuhiro Kondoh Tomoki Kimura Kensuke Kataoka Osamu Nishiyama Masashi Kondo Yoshinori Hasegawa 《International journal of clinical oncology / Japan Society of Clinical Oncology》2014,19(2):260-265
Background
Idiopathic pulmonary fibrosis (IPF) is associated with an independent increased risk of lung carcinogenesis. The benefit of chemotherapy for extensive-stage small-cell lung cancer (ED-SCLC) in cases of IPF remains unknown. This study was conducted to elucidate the efficacy of chemotherapy for ED-SCLC in patients with IPF.Methods
This was a retrospective observational study of ED-SCLC patients with IPF (all with distant metastasis) who received systemic chemotherapy. The response rate, toxicity, overall survival, and progression-free survival (PFS) were investigated.Results
Eleven patients treated with chemotherapy between January 2005 and December 2011 were the subjects of this study. The overall response rate with the 1st regimen was 63.6 %. The median overall survival was 7.0 months, and the median PFS was 4.7 months.Conclusion
Our results suggest that ED-SCLC patients with IPF may benefit from chemotherapy. A prospective study will be needed to confirm this in the future. 相似文献11.
Yan Wang Yi-yi Yu Wei Li Yi Feng Jun Hou Yuan Ji Yi-hong Sun Kun-tang Shen Zhen-bin Shen Xin-yu Qin Tian-shu Liu 《Cancer chemotherapy and pharmacology》2014,73(6):1155-1161
Purpose
Gastric cancer with para-aortic lymph node (PAN) involvement is regarded as advanced disease, and only chemotherapy is recommended from the guidelines. In unresectable cases, neoadjuvant chemotherapy could prolong survival if conversion to resectability could be achieved.Methods
The study was a single-arm phase II trial. Patients who were diagnosed with gastric cancer and PAN involvement (Stations No. 16a2/16b1) were treated with capecitabine and oxaliplatin combination chemotherapy every 3 weeks for a maximum of six cycles. After every two cycles, abdominal computed tomographic scans were repeated to evaluate the response, and surgery was performed at the physician’s discretion in patients with sufficient tumor response, followed by chemotherapy with the same regimen to complete a total of six cycles. The primary end point was the response rate of the preoperative chemotherapy. The secondary end points were R0 resection rate, progression-free survival (PFS), overall survival (OS), and adverse events.Results
A total of 48 patients were enrolled. The response rate of the first-line chemotherapy was 49.0 %, and the clinical benefit response was 85.1 %. After a median of four cycles of chemotherapy, 28 patients received surgery (58.3 %). The median PFS and OS of all patients were 10.0 and 29.8 months, respectively. Patients in the surgery group had much longer PFS (18.1 vs. 5.6 mo, P = 0.001) and OS (not reached vs. 12.5 mo, P = 0.016) compared with those in the non-surgery group.Conclusions
For gastric cancer patients with PAN involvement, neoadjuvant chemotherapy with XELOX demonstrated a good response rate, and a sufficient R0 resection rate, with acceptable toxicities. Further study is needed to confirm the effectiveness of this regimen. 相似文献12.
Shunsuke Okazaki Takako E. Nakajima Jun Hashimoto Seiichiro Yamamoto Daisuke Takahari Ken Kato Tetsuya Hamaguchi Yasuhide Yamada Yasuhiro Shimada Kenji Tamura 《Gastric cancer》2013,16(1):41-47
Background
Regimens of standard-dose cisplatin have usually been administered as inpatient chemotherapy in Japan. This prospective study evaluated the feasibility of outpatient chemotherapy with standard-dose cisplatin in Japanese patients with advanced gastric cancer.Methods
Advanced gastric cancer patients received an S-1 + cisplatin regimen (S-1: 80–120 mg days 1–21; cisplatin: 60 mg/m2 day 8, every 4–5 weeks), either as outpatient chemotherapy with oral hydration on days 9–10, or as inpatient chemotherapy with intravenous hydration on days 9–10, based on the results of an oral hydration test during days 1–7 of the first cycle. The primary endpoint was the completion rate of two cycles in the outpatient group.Results
A total of 36 patients were enrolled: 32 were allocated to the outpatient group and 4 to the inpatient group. The completion rate of two cycles in the outpatient group was 78% [90% confidence interval (CI): 63–89]. The median of the total number of treatment cycles of S-1 + cisplatin and the median progression-free survival in the outpatient group were 5 (range 1–11) and 10.6 months (95% CI 4.2–16.9), respectively. Although seven patients in the outpatient group discontinued treatment, mainly owing to gastrointestinal toxicity, most of them could continue S-1 + cisplatin by switching to inpatient chemotherapy from the next cycle.Conclusion
Outpatient chemotherapy with S-1 + cisplatin in advanced gastric cancer patients can be safely and effectively administered in Japan with appropriate patient selection and supportive treatment. 相似文献13.
Takaki Yoshikawa Akira Tsuburaya Ken Shimada Atsushi Sato Makoto Takahashi Wasaburo Koizumi Yasuo Yoshizawa Kazuhito Nabeshima Masayuki Kimura Kiyoshi Hataya Osamu Kobayashi 《Gastric cancer》2009,12(4):212-218
Background
The aim of this study was to establish the efficacy and safety of doxifluridine and docetaxel for patients with advanced or recurrent gastric cancer.Methods
The regimen consisted of oral administration of doxifluridine 533 mg/m2 per day on days 1–14 and an intravenous infusion of docetaxel 50 mg/m2 on day 8. The primary endpoint was the overall response rate. The secondary endpoints were overall survival, progression-free survival, and toxicities.Results
Between June 2004 and December 2006, a total of 40 eligible patients were enrolled in this study. Seven of them showed a partial response, with an overall response rate of 17.5%. The response rate was 18.8% in 32 patients with refractory tumors. The median progression-free survival time and the median overall survival time were 2.6 months and 12.7 months, respectively, in all 40 patients; and 2.6 months and 14.0 months, respectively, in the 32 patients with refractory tumors. Grade 3/4 hematological toxicity included neutropenia in 52.5%, leukocytopenia in 17.5%, and febrile neutropenia in 7.5%. Grade 3 or more nonhematological toxicities were infrequent.Conclusion
The combination chemotherapy of doxifluridine and docetaxel was well tolerated and relatively effective when used as a second-line chemotherapy for advanced or recurrent gastric cancer. 相似文献14.
Valentina Fanotto Stefano Cordio Giulia Pasquini Caterina Fontanella Lorenza Rimassa Francesco Leone Gerardo Rosati Daniele Santini Riccardo Giampieri Samantha Di Donato Gianluca Tomasello Nicola Silvestris Filippo Pietrantonio Francesca Battaglin Antonio Avallone Mario Scartozzi Eufemia Stefania Lutrino Davide Melisi Lorenzo Antonuzzo Antonio Pellegrino Valter Torri Giuseppe Aprile 《Gastric cancer》2017,20(5):825-833
Background
Although second-line therapy is often considered for advanced gastric cancer patients, the optimal candidates are not well defined.Methods
We retrospectively collected baseline parameters, tumour features, and treatment data for 868 advanced gastric cancer patients exposed to multiple treatment lines at 19 Italian centres. Cross-tables and chi-square tests were used to describe categorical features. To predict the impact of clinical variables on progression-free survival and overall survival, Kaplan–Meier and Cox regression analyses were performed.Results
At the start of second-line therapy, median age was 64.8 years (25th–75th percentiles: 55.2–71.9 years). Overall, 43% of patients received single-agent chemotherapy, 47.4% a doublet, and 7.3% a triplet. Median second-line progression-free survival was 2.8 months (25th–75th percentiles: 1.8–5.2 months) and median second-line overall survival was 5.6 months (25th–75th percentiles: 2.9–10.0 months). Multivariate analysis showed that performance status, LDH level, neutrophils/lymphocytes ratio, and progression-free survival in the first-line therapy all impacted on prognosis. Based on these four prognostic factors, a prognostic index was constructed that divided patients into good, intermediate, and poor risk groups; median second-line overall survival for each group was 7.7, 4.5, and 2.0 months, respectively (log-rank p < 0.0001).Conclusions
Advanced gastric cancer patients with a favourable ECOG performance status, lower LDH levels, and a lower neutrophils/lymphocytes ratio at the start of second-line therapy seem to have better outcomes, regardless of age and intensity of treatment. A longer progression-free survival in the first-line therapy also had positive prognostic value. Our real-life study might help clinicians to identify the patients who may benefit most from a second-line therapy.15.
Simon Pernot Emmanuel Mitry Emmanuelle Samalin Laetitia Dahan Cécile Dalban Marc Ychou Jean-François Seitz Hajer Turki Thibault Mazard Aziz Zaanan Céline Lepère Jean-Nicolas Vaillant Bruno Landi Philippe Rougier Julien Taieb 《Gastric cancer》2014,17(2):341-347
Background
Docetaxel–cisplatin-5-FU chemotherapy is superior to 5-FU-cisplatin in terms of response rate and survival in advanced gastric cancer (AGC), but is more toxic. Oxaliplatin is better tolerated than cisplatin, which it can effectively replace in this setting. We hypothesize that incorporating docetaxel into a simplified FOLFOX regimen should be a tolerable and effective option in first-line treatment of AGC.Methods
Data were collected at six French centers from patients with metastatic or local AGC who received docetaxel, fluorouracil, leucovorin, or oxaliplatin (TEF) as first-line treatment. TEF was administered as follows: docetaxel (50 mg/m2), oxaliplatin (85 mg/m2), and leucovorin (40 mg/m2) on day 1, and 5-FU continuous infusion for 48 h (2400 mg/m2) every 2 weeks.Results
Forty-one patients were enrolled. Performance status was grade 0 and 1 in respectively 27 and 58 % of patients; 17 patients had adenocarcinoma of the gastroesophageal junction; 37 patients had metastatic disease, 22 had a poorly differentiated or diffuse type. Objective response rate was 66 %, with a complete response in two patients (5 %). Median progression-free survival and overall survival were respectively 6.3 and 12.1 months. Tolerability was acceptable with no treatment-related deaths. The most frequent grade 3–4 toxicities were neutropenia (30 %) and neuropathy (12.5 %). Curative intent surgery after response to TEF was performed in seven patients (17 %).Conclusion
TEF is an effective first-line treatment with an acceptable toxicity profile for patients with AGC. It may allow curative resection in initially unresectable patients. TEF should now be evaluated in prospective randomized trials. 相似文献16.
Hideaki Miyake Yuji Kusuda Ken-ichi Harada Iori Sakai Masato Fujisawa 《International journal of clinical oncology / Japan Society of Clinical Oncology》2013,18(1):81-86
Background
The aim of this study was to evaluate the use of sunitinib as third-line therapy for metastatic renal cell carcinoma (mRCC).Methods
This study included a total of 35 consecutive Japanese patients with mRCC who were treated with third-line sunitinib after sequential use of cytokine therapy (interferon-α and/or interleukin-2) and sorafenib between September 2008 and December 2010. The clinical outcomes of third-line sunitinib in these patients were retrospectively reviewed.Results
Of the 35 patients, 3 (8.6%), 28 (80.0%) and 4 (11.4%) were judged to have a partial response, stable disease and progressive disease, respectively, as the best response to sunitinib. The median progression-free survival (PFS) and overall survival (OS) of these patients following the introduction of sunitinib were 10.9 and 14.2 months, respectively. Of several factors examined, response to sorafenib and performance status appeared to be independently associated with PFS and OS, respectively, on multivariate analyses. The common grade 3–4 adverse events related to third-line sunitinib were thrombocytopenia (51.4%), neutropenia (42.9%) and hypertension (14.3%).Conclusion
Despite the low response rate, third-line sunitinib is well tolerated and could provide comparatively favorable prognostic outcomes in Japanese patients with mRCC after first-line cytokine therapy and second-line sorafenib; therefore, treatment with sunitinib could be one on the therapeutic options for patients with mRCC even after the failure of sequentially performed systemic therapies, such as cytokine therapy and sorafenib. 相似文献17.
Gouji Toyokawa Mitsuhiro Takenoyama Fumihiko Hirai Ryo Toyozawa Eiko Inamasu Miyako Kojo Yosuke Morodomi Yoshimasa Shiraishi Tomoyoshi Takenaka Masafumi Yamaguchi Mototsugu Shimokawa Takashi Seto Yukito Ichinose 《International journal of clinical oncology / Japan Society of Clinical Oncology》2014,19(4):601-606
Background
Malignant pleural mesothelioma (MPM) is an aggressive neoplasm that responds poorly to chemotherapy. Although treatment with pemetrexed in combination with cisplatin serves as first-line chemotherapy for MPM, the optimal second-line and beyond therapy has not yet been fully examined.Methods
Between March 2008 and October 2011, 17 consecutive Japanese patients pretreated with at least one regimen of platinum plus pemetrexed chemotherapy received gemcitabine and vinorelbine. Responses, survival time, and toxicity were retrospectively evaluated.Results
Response [partial response (PR) + complete response (CR)] and disease control [stable disease (SD) + PR + CR] rates were 18 and 82 %, respectively. The median progression-free survival (PFS) after combination chemotherapy was 6.0 months, whereas the median overall survival (OS) was 11.2 months. Grade 3 or 4 neutropenia and anemia were observed in 41 and 29 % of patients, respectively, and one patient experienced febrile neutropenia. Grade 3 or 4 nonhematologic toxicities included constipation (6 %) and phlebitis (6 %).Conclusion
Combination chemotherapy using gemcitabine with vinorelbine was shown to have moderate activity in Japanese MPM patients pretreated with platinum plus pemetrexed chemotherapy. A further multicenter phase II trial is warranted to confirm the efficacy and safety of this combination treatment. 相似文献18.
D. Marquez-Medina A. Chachoua A. Martin-Marco A. M. Desai V. Garcia-Reglero A. Salud-Salvia F. Muggia 《Clinical & translational oncology》2013,15(11):959-964
Purpose
Advanced non-small cell lung cancer (NSCLC) is a common and lethal malignancy that has rarely benefited from chemotherapy. Erlotinib is highly effective in NSCLC patients selected by clinical characteristics and/or the presence of epidermal growth factor receptor-sensitizing mutations. However, the way to delay or bypass erlotinib resistance is not systematically addressed. Different erlotinib-failure modes have been reported in NSCLC, and strategies to prolong erlotinib efficacy are perhaps adaptable to them. We report the feasibility and efficacy of continued erlotinib maintenance and local salvage radiation to overcome erlotinib resistances in selected NSCLC patients.Patients and methods
Thirty of 52 consecutive erlotinib-treated advanced NSCLC from the NYU Langone Medical Center and the Arnau de Vilanova Hospital of Lleida responded initially to erlotinib. Twenty-six patients eventually showed a generalized-progression to erlotinib, and four progressed in solitary tumor sites. These four patients were treated with continued erlotinib maintenance and local salvage radiation.Results
The progression-free survival (PFS) was statistically similar in patients with oligo or generalized-progression to erlotinib. However, all four cases with solitary-progression did benefit from continued erlotinib maintenance and salvage radiation with 41–140 % prolongation of PFS. It was reflected in an improved overall survival when they were compared with patients with generalized-progression (76.4 vs. 19.9 months; p = 0.018).Conclusion
Continued erlotinib maintenance and local salvage radiation is feasible and could contribute to a better outcome in selected NSCLC patients with solitary-progression to erlotinib. Prospective randomized trials of this strategy are warranted. 相似文献19.
Masahiro Morimoto Fumiaki Isohashi Yasuo Yoshioka Osamu Suzuki Yuji Seo Toshiyuki Ogata Yuichi Akino Masahiko Koizumi Kazuhiko Ogawa 《International journal of clinical oncology / Japan Society of Clinical Oncology》2014,19(2):312-318
Background
We retrospectively examined outcomes of salvage high-dose-rate interstitial brachytherapy (HDR-ISBT) for locally recurrent rectal cancer (LRRC).Methods
Nine patients with LRRC were treated with salvage HDR-ISBT. Their median age was 63 years. The median maximum diameter of LRRC was 40 mm (range 20–80 mm). Adenocarcinomas were histologically confirmed in all cases. The prescribed dose was 30 Gy/5 fractions/3 days to 50 Gy/10 fractions/6 days in the combined external-beam radiotherapy group (four patients) and 54 Gy/9 fractions/5 days to 60 Gy/10 fractions/6 days in the monotherapeutic group (five patients). Median follow-up time was 90 months (range 6–221 months).Results
Local control at final follow-up was achieved in five of nine patients. Of these five patients, one experienced a locally re-recurrent tumor in the vaginal wall 33 months after treatment and received re-HDR-ISBT as re-salvage treatment. The 8-year overall survival, local control, and progression-free survival rates were 56, 44, and 33 %, respectively. Based on the Common Terminology Criteria for Adverse Events ver. 4.03, the following Grade 3 adverse events were observed in three patients (≥3 months): Grade 3 skin ulceration in one patient who showed tumor invasion of the skin and whose V100 was 400 cc; Grade 3 vaginal perforation in one patient whose tumor had invaded the vaginal wall; and Grade 3 vagina-to-bladder fistula in one patient whose tumor received re-irradiation. Late adverse events above Grade 3 were not observed.Conclusions
Long-term follow-up results revealed that salvage HDR-ISBT is a promising treatment for LRRC with tolerable toxicity. 相似文献20.
Kunitoshi Shigeyasu Shunsuke Kagawa Futoshi Uno Masahiko Nishizaki Hiroyuki Kishimoto Akira Gochi Toshikazu Kimura Takaomi Takahata Yasuyuki Nonaka Motoki Ninomiya Toshiyoshi Fujiwara 《Cancer chemotherapy and pharmacology》2013,71(4):937-943