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1.
Yoda S Soejima K Yasuda H Naoki K Kawada I Watanabe H Nakachi I Satomi R Nakayama S Ikemura S Terai H Sato T Morosawa M Asano K 《Cancer chemotherapy and pharmacology》2011,67(3):717-722
Background
This phase I study was conducted to evaluate the feasibility and to determine the recommended doses of the combination therapy of S-1 and irinotecan (CPT-11) in patients with advanced non-small cell lung cancer (NSCLC) as second-line treatment.Methods
Patients with NSCLC who were previously treated with one chemotherapy regimen and had a performance status of 0 or 1 were eligible. CPT-11 was administered at 60 mg/m2 (level 1), 80 mg/m2 (level 2) on days 1 and 8, and oral S-1 was administered at 80 mg/day for body surface area (BSA) less than 1.25 m2, 100 mg/day for BSA 1.25–1.5 m2, and 120 mg/day for BSA more than 1.5 m2 on days 1–14 every 3 weeks. The dose-limiting toxicity (DLT) was defined as grade 4 leukocytopenia or neutropenia, grade ≥3 neutropenia with fever over 38°C, grade ≥3 thrombocytopenia, or grade ≥3 major nonhematological toxicities.Results
Nine patients were enrolled in the study. None of 3 patients enrolled in level 1 had any DLT. Of 6 patients in level 2, 2 patients had grade 3 diarrhea and one had grade 3 interstitial pneumonia. Level 1 was declared as the recommended dose.Conclusion
The feasibility of the combination therapy of S-1 and CPT-11 was shown in the second-line setting for the treatment of advanced NSCLC. The recommended dose of CPT-11 was 60 mg/m2 combined with standard dose of S-1 for phase II trials of pretreated advanced NSCLC patients. 相似文献2.
Phase I study of irinotecan and S-1 combination therapy in patients with metastatic gastric cancer 总被引:3,自引:0,他引:3
Yamada Y Yasui H Goto A Arai T Ura T Hamaguchi T Muro K Shimada Y Shirao K 《International journal of clinical oncology / Japan Society of Clinical Oncology》2003,8(6):374-380
Background Irinotecan plus intravenous 5-fluorouracil with leucovorin is effective against gastrointestinal cancer. S-1 is an oral fluoropyrimidine derivative combining tegafur with the modulators 5-chloro-2,4-dihydroxypyrimidine (a potent dihydropyrimidine dehydrogenase inhibitor), and potassium oxonate (an orotate phosphoribosyl transferase inhibitor), in a molar ratio of 1:0.4:1. S-1 has a high response rate, of about 40%, in advanced gastric cancer. A phase I study was conducted to assess the maximum tolerated dose and the recommended dose of the combination of irinotecan and S-1.Methods Irinotecan was given intravenously over the course of 90min on day 1 and S-1 was given orally from days 1 to 14 of a 21-day cycle. The dose of S-1 was 80mg/m2 per day, given in two divided doses. The dose of irinotecan was escalated in a stepwise fashion from 100mg/m2 (level 1; n = 3), to 125mg/m2 (level 2; n = 3), and 150mg/m2 (level 3; n = 6).Results Dose-limiting toxicity did not occur during cycle 1, and the recommended dose for phase II studies was determined to be level 3, which was associated with grade 3 diarrhea in one patient, and with refusal to continue treatment because of prolonged fatigue in two patients. Grade 3 neutropenia developed in one of three patients at level 1 and level 2, and in two of six during cycle 1 of level 3. The recommended dose was determined to be 150mg/m2 of irinotecan on day 1 and 80mg/m2 per day of S-1 on days 1 to 14 of a 21-day cycle. Five of seven patients with measurable lesions had a partial response.Conclusions A combination of irinotecan and S-1 can be recommended for further phase II studies in patients with gastric cancer. 相似文献
3.
Yoon-Koo Kang 《Gastric cancer》2009,12(1):38
Despite the progress in treatment protocols, gastric cancer remains a challenging disease. Systemic chemotherapy is of crucial importance for patients with metastatic or recurrent disease, and new developments in chemotherapy regimens have been seen in recent years. An oral 5-fluororacil (5-FU) agent, S-1, is emerging, with promising results. Various S-1 combination regimens, mostly with cisplatin, are being examined extensively, and the combination of S-1 with oxaliplatin is the focus of recent studies. In this study, phase I/II studies of combination chemotherapy with S-1 and platinum in patients with metastatic or recurrent gastric cancer were reviewed. We found that the combination of S-1 plus cisplatin was highly active against advanced gastric cancer, with a favorable toxicity profile. The response rates were 53%-74% in Japan, 47.6% in Korea, and 51% in the United States and Europe. There is no internationally accepted standard care for patients with advanced gastric cancer yet, but S-1 is likely to replace infusional 5-FU, and oxaliplatin may represent an alternative to cisplatin in the near future. More innovative therapies, particularly with molecular-targeted drugs, are needed to meet the needs of patients in the era of tailored medicine. 相似文献
4.
Yoon-Koo Kang 《Gastric cancer》2009,12(Z1):38-42
Despite the progress in treatment protocols, gastric cancer remains a challenging disease. Systemic chemotherapy is of crucial
importance for patients with metastatic or recurrent disease, and new developments in chemotherapy regimens have been seen
in recent years. An oral 5-fluororacil (5-FU) agent, S-1, is emerging, with promising results. Various S-1 combination regimens,
mostly with cisplatin, are being examined extensively, and the combination of S-1 with oxaliplatin is the focus of recent
studies. In this study, phase I/II studies of combination chemotherapy with S-1 and platinum in patients with metastatic or
recurrent gastric cancer were reviewed. We found that the combination of S-1 plus cisplatin was highly active against advanced
gastric cancer, with a favorable toxicity profile. The response rates were 53%-74% in Japan, 47.6% in Korea, and 51% in the
United States and Europe. There is no internationally accepted standard care for patients with advanced gastric cancer yet,
but S-1 is likely to replace infusional 5-FU, and oxaliplatin may represent an alternative to cisplatin in the near future.
More innovative therapies, particularly with molecular-targeted drugs, are needed to meet the needs of patients in the era
of tailored medicine. 相似文献
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Sym SJ Chang HM Kang HJ Lee SS Ryu MH Lee JL Kim TW Yook JH Oh ST Kim BS Kang YK 《Cancer chemotherapy and pharmacology》2008,63(1):1-8
Purpose Irinotecan (I) and docetaxel (D), each of which has a unique mechanism of action, were recently introduced in the treatment
of patients with advanced gastric cancer (AGC). We have evaluated the efficacy and safety of the ID combination for AGC patients
after failure of fluoropyrimidine- or platinum-based chemotherapy.
Materials and methods Patients with relapsed or progressive AGC after prior fluoropyrimidine- or platinum-based chemotherapy were treated with I
(160 mg/m2, 90 min) followed by D (65 mg/m2, 1 h) every 3 weeks. Because of the unacceptable toxicity among the first ten patients, the doses were reduced for I (120 mg/m2) and D (50 mg/m2) every 3 weeks.
Results Forty-nine patients, of median age 53 years (range, 27–68 years), were treated with 170 cycles of chemotherapy (median, 2
cycles; range, 1–12 cycles). Three patients achieved complete response and seven achieved partial response, resulting in an
overall response rate (ORR) of 20.4% [95% confidence interval (CI), 9.1–31.7%], with a median duration of 7.1 months (range:
2.1–69.1 months). ORR was 60% (95% CI, 29.6–90.3%) for the higher dose and 10.3% (95% CI, 0.7–19.8%) for the lower dose. Median
time to progression for all patients was 2.7 months (95% CI, 1.7–3.8 months) and the median overall survival was 8.9 months
(95% CI, 6.6–11.3 months). Grade 3/4 toxicities included neutropenia (90%), febrile neutropenia (50%), asthenia (40%), and
diarrhea (10%) with the higher dose and neutropenia (71%), febrile neutropenia (11%), diarrhea (24%), and asthenia (24%) with
the lower dose. There were two possible treatment-related deaths.
Conclusion The combination of irinotecan and docetaxel, once every three weeks shows anti-tumor activity but is not feasible as a second-line
treatment for AGC patients after failure of fluoropyrimidine- or platinum-based chemotherapy due to the high rate of toxicities.
S. J. Sym and H. M. Chang
have contributed equally to this article. 相似文献
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《Annals of oncology》2012,23(1):119-127
BackgroundThis study evaluated the maximum tolerated dose (MTD) of sunitinib, a multitargeted tyrosine kinase inhibitor, combined with FOLFIRI (irinotecan 180 mg/m2 given over 90 min i.v. and l-leucovorin 200 mg/m2 given over 120 min on day 1, followed by 5-FU 400 mg/m2 bolus and then 2400 mg/m2 infused over 46 h) in untreated metastatic colorectal cancer (mCRC).Patients and methodsIn this multicentre, phase I, open-label, dose-finding trial, FOLFIRI was administered every 2 weeks. Two sunitinib regimens were explored: Schedule 4/2 (4 weeks on, 2 weeks off; 37.5 and 50 mg/day) and continuous daily dosing (CDD; 37.5 and 25 mg/day). Dose-limiting toxic toxicities (DLTs) were evaluated during weeks 1–6. Efficacy was a secondary objective.ResultsThirty-seven patients were enrolled. The 37.5 mg/day Schedule 4/2 cohort had zero of six DLTs, was expanded by 15 patients and declared the MTD. The MTD was exceeded at all other sunitinib doses and schedules; DLTs included febrile neutropenia (n = 1), grade 4 neutropenia (n = 4) and grade 3 deep vein thrombosis with grade 4 neutropenia (n = 1). At the MTD, non-haematologic grade 3/4 adverse events with a frequency of >10% were diarrhoea, vomiting and lethargy, and the objective response rate was 57.9% (95% confidence interval 33.5–79.7).ConclusionsThe MTD of sunitinib combined with FOLFIRI in chemotherapy-naive mCRC was 37.5 mg/day on Schedule 4/2. CDD of sunitinib at 37.5 or 25 mg/day plus FOLFIRI was not feasible. 相似文献
9.
Manabu Shiozawa Makoto Akaike Nobuhiro Sugano Kazuhito Tsuchida Naoto Yamamoto Soichiro Morinaga 《Cancer chemotherapy and pharmacology》2010,66(5):987-992
Purpose
A combination of irinotecan with continuous infusional 5-fluorouracil (5-FU) is the standard treatment for advanced colorectal cancer. The aim of this study was to determine the efficacy and safety of combining irinotecan and S-1 (IRIS) in patients with advanced colorectal cancer.Methods
Irinotecan was administered as an intravenous infusion at a dose of 120 mg/m2 on day 1 and 15. And S-1 was administered orally on days 1–14 of a 28-day cycle. S-1 was given orally at a dose that did not exceed 40 mg/m2 based BSA: BSA < 1.25 m2, 40 mg twice daily; 1.25–1.5 m2, 50 mg twice daily, and BSA > 1.5 m2, 60 mg twice daily, for 14 consecutive days.Results
A total of 38 patients were enrolled. An intent-to-treat analysis showed a complete response and partial response to occur in 13.2% and 50.0%, respectively. The disease control rate was 84.2%. The median progression-free survival and overall survival were 10.0 months and 29.1 months, respectively. The rates of grade 3/4 toxicity over 4 cycles were the following: neutropenia, 15.8%; leucopenia, 7.9%; anorexia, 15.8%; diarrhea, 10.5%. Conclusion: IRIS is an effective, well tolerated and convenient treatment regimen for patients with advanced colorectal cancer. 相似文献10.
11.
T Yoshioka S Kato M Gamoh N Chiba T Suzuki N Sakayori S Kato H Shibata H Shimodaira K Otsuka Y Kakudo S Takahashi C Ishioka 《British journal of cancer》2009,101(12):1972-1977
Background:
Both irinotecan (CPT-11) and S-1 are active against colorectal cancer; however, as S-1 is a prodrug of 5-fluorouracil (5-FU), 5-FU and its metabolites might inhibit the antitumour effect of CPT-11. Therefore, we designed a sequential combination, in which CPT-11 infusion was given on day 1 and S-1 was given orally at 80 mg m−2 per day on days 3–16 every 3 weeks.Methods:
Twelve patients entered the phase I study, and the recommended doses were determined as a CPT-11 dose of 150 mg m−2 and an S-1 dose of 80 mg m−2.Results:
In all, 36 patients entered the phase II study, of whom 4 and 16 had complete and partial responses. The overall response rate was 55.6% (95% confidence interval, 38.1–72.1%), and median progression-free survival was 7.7 months (95% confidence interval, 4.8–12.6 months). Grade 3 neutropenia was the most common haematological toxicity and occurred in 6.5% of 215 treatment courses. Grade 3 non-haematological toxicities included anorexia (1.4%) and diarrhoea (0.9%). There was no grade 4 toxicity of any kind.Conclusion:
Our results suggest that this regimen is convenient, safe and promising, compared with conventional regimens for patients with metastatic colorectal cancer. 相似文献12.
A Goto Y Yamada H Yasui K Kato T Hamaguchi K Muro Y Shimada K Shirao 《Annals of oncology》2006,17(6):968-973
BACKGROUND: A combination of irinotecan with continuous intravenous infusions of 5-fluorouracil (5-FU) and leucovorin (LV) is often used to treat advanced colorectal cancer. However, recent concerns about safety and convenience have prompted the development of new oral fluoropyrimidine derivatives and improved regimens. This phase II study evaluated the efficacy and safety of the oral fluoropyrimidine S-1 plus irinotecan in patients with previously untreated advanced or recurrent colorectal cancer. PATIENTS AND METHODS: Forty eligible patients with histologically confirmed colorectal adenocarcinoma received this treatment. S-1 was administered orally on days 1 to 14 of a 21-day cycle. Patients were assigned on the basis of body surface area (BSA) to receive one of the following oral doses twice daily: 40 mg (BSA < 1.25 m(2)), 50 mg (BSA > or = 1.25 to < 1.50 m(2)), or 60 mg (BSA > or = 1.50 m(2)). Irinotecan (150 mg/m(2)) was administered by intravenous infusion on day 1. RESULTS: A total of 327 courses of treatment were administered to 40 patients. Five patients had complete responses, and 20 had partial responses. The overall response rate was 62.5% (95% confidential interval, 47.5%-77.5%). Median progression-free survival was 8.0 months (95% confidential interval, 5.2-11.4 months). The rates of grade 3 or 4 toxicity were as follows: neutropenia, 15%; anemia, 7.5%; anorexia, 12.5%; and diarrhea, 7.5%. CONCLUSIONS: Combined treatment with S-1 and irinotecan is an effective, well tolerated, and convenient regimen in patients with advanced colorectal cancer. Our findings suggest that combined treatment with S-1 and irinotecan is a promising regimen, offering benefits in terms of safety and survival as compared with conventional regimens in patients with advanced colorectal cancer. 相似文献
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H. Kennecke L. Chen C.D. Blanke W.Y. Cheung K. Schaff C. Speers 《Current oncology (Toronto, Ont.)》2013,20(6):326-332
Background
The survival benefit for single-agent anti–epidermal growth factor receptor (egfr) therapy compared with combination therapy with irinotecan in KRAS wildtype (wt) metastatic colorectal cancer (mcrc) patients in the third-line treatment setting is not known. The objective of the present study was to describe the characteristics of, and to compare survival outcomes in, two cohorts of patients treated with either singleagent panitumumab or combination therapy with cetuximab and irinotecan.Methods
The study enrolled patients with KRAS wt mcrc previously treated with both irinotecan and oxaliplatin who had received either panitumumab or combination cetuximab–irinotecan before April 1, 2011, at the BC Cancer Agency (bcca). Patients were excluded if they had received anti-egfr agents in earlier lines of therapy. Data were prospectively collected, except for performance status (ps), which was determined by chart review. Information about systemic therapy was extracted from the bcca Pharmacy Database.Results
Of 178 eligible patients, 141 received panitumumab, and 37 received cetuximab–irinotecan. Compared with patients treated with cetuximab–irinotecan, panitumumab-treated patients were significantly older and more likely to have an Eastern Cooperative Oncology Group (ecog) ps of 2 or 3 (27.7% vs. 2.7%, p = 0.001). Other baseline prognostic variables and prior and subsequent therapies were similar. Median overall survival was 7.7 months for the panitumumab group and 8.3 months for the cetuximab–irinotecan group. Multivariate analysis demonstrated that survival outcomes were similar regardless of the therapy selected (hazard ratio: 1.28; p = 0.34). An ecog ps of 2 or 3 compared with 0 or 1 was the only significant prognostic factor in this treatment setting (hazard ratio: 3.37; p < 0.01).Conclusions
Single-agent panitumumab and cetuximab–irinotecan are both reasonable third-line treatment options, with similar outcomes, for patients with chemoresistant mcrc. 相似文献16.
Toshi Takaoka Tetsuo Kimura Rai Shimoyama Shunji Kawamoto Kazuki Sakamoto Fuminori Goda Hiroshi Miyamoto Yuji Negoro Akihito Tsuji Koji Yoshizaki Takahiro Goji Shinji Kitamura Hiromi Yano Koichi Okamoto Masako Kimura Toshiya Okahisa Naoki Muguruma Yoshiro Niitsu Tetsuji Takayama 《Cancer chemotherapy and pharmacology》2016,78(2):397-403
17.
N Kemeny W Tong M Gonen J Stockman C Di Lauro J Teitcher P White C Price L Saltz S Sharma M A Graham 《Annals of oncology》2002,13(9):1490-1496
BACKGROUND: In vitro synergy between Oxal (oxaliplatin) and CPT-11 (irinotecan) has been reported. Oxaliplatin exerts its antineoplastic activity through the formation of platinum-DNA adducts. Resistance to oxaliplatin is through repair of these adducts, which is inhibited by irinotecan. PATIENTS AND METHODS: Oxaliplatin and irinotecan were administered weekly for 4 weeks followed by a 2-week rest period. The dose of oxaliplatin was escalated first, starting at 30 mg/m(2). Once a dose of 60 mg/m(2) was attained, the weekly dose of irinotecan was escalated, from 40 mg/m(2) to 85 mg/m(2). A total of 49 previously treated patients with metastatic colorectal cancer were entered in order to establish the maximum tolerated dose. Pharmacokinetics of oxaliplatin and irinotecan were analyzed. RESULTS: Forty-nine patients were evaluable for toxicity. The recommended phase II doses for this combination are oxaliplatin 60 mg/m(2) and irinotecan 50 mg/m(2), weekly x 4 q 6 weeks. Diarrhea was the most common dose-limiting toxicity. No pharmacological interactions were noted between oxaliplatin and irinotecan. Twelve of the 47 evaluable patients (26%) achieved a partial response. CONCLUSION: Weekly combination of oxaliplatin and irinotecan appears to be a well tolerated and active regimen in patients previously treated for metastatic colorectal cancer. Further investigations of this regimen are warranted. 相似文献
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《Annals of oncology》2010,21(9):1810-1816
BackgroundThis study compared irinotecan plus cisplatin (IP) with etoposide plus cisplatin (EP) in small-cell lung cancer patients with extensive disease.Patients and methodsPatients were randomly assigned to receive cisplatin 80 mg/m2 and either irinotecan 65 mg/m2, days 1 and 8 or etoposide 100 mg/m2, days 1–3, every 3 weeks.ResultsBaseline characteristics were balanced between patients receiving IP (N = 202) or EP (N = 203). Median overall survival was nonsignificantly superior for patients receiving IP versus EP, 10.2 versus 9.7 months [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.65–1.01, P = 0.06] and 1- and 2-year survival rates were 41.9% versus 38.9% and 16.3% versus 8.2%, respectively. Noninferiority of IP versus EP was established, upper bound of the 95% CI of HR 1.01 (prespecified margin IP/EP <1.25). Overall response (39.1% versus 46.6%) and time to tumor progression (5.4 versus 6.2 months) were not superior for IP. Grade 3/4 vomiting (10.9% versus 4.4%) and diarrhea (15.4% versus 0.5%) were more common in the IP versus EP arm; grade 3/4 neutropenia was more frequent in the EP (59.6%) versus IP arm (38.1%).ConclusionsOur data demonstrate the noninferiority of IP versus EP for survival in primarily Western patients with SCLC-ED. A meta-analysis is required to finally assess the role of irinotecan in this setting. 相似文献
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A. Sabharwal P. G. Corrie R. S. Midgley C. Palmer J. Brady P. Mortimer A. J. Watson G. P. Margison M. R. Middleton 《Cancer chemotherapy and pharmacology》2010,66(5):829-835