Phase I/II study of arterial infusion with 5-fluorouracil combined with systemic gemcitabine for unresectable pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 307-307 ◽  
Author(s):  
T. Tanaka ◽  
H. Nishiofuku ◽  
M. Sho ◽  
H. Anai ◽  
S. Sueyoshi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Phase Ii ◽  
Tumor Response ◽  
Response Rate ◽  
Survival Duration ◽  
Unresectable Pancreatic Cancer ◽  
Survival Times ◽  
Arterial Infusion ◽  
Port System

307 Background: Unresectable pancreatic cancer is poorly responsive to conventional therapies. We conducted a phase I/II study to ascertain the recommended dose (RD) of 5-fluorouracil (5-FU) in arterial infusion chemotherapy combined with systemic gemcitabine in unresectable pancreatic cancer and to evaluate the safety and efficacy. Methods: 5-FU was administered through the pancreatic and hepatic arteries via the port system as a 5-hour infusion on days 1, 8, and 15 every 4 weeks for 5 cycles. Gemcitabine was administered in 30-minute intravenous infusion at the same days. In phase I, escalating 5-FU doses for level 1 and 2 was set at 750mg and 1,000mg/m2, respectively. Dose of coadministered gemcitabine (1,000 mg/m2) was fixed. Using a 3+3 study design, dose-limiting toxicity (DLT) was assessed, and RD was estimated in the first cycle. In phase II, more RD patients were added to assess tumor response, toxicity, overall survival and progression-free survival. Results: During the phase I, 7 patients were enrolled. DLT was not observed. One patient dropped out of this study because of insufficient drug distribution via the port system. Assuming RD at 1,000mg/m2 of 5-FU, the phase II enrolled a total of 16 patients (metastatic, 14; local advanced, 2). The tumor response rate was 68.8% (CR 0, PR 11, SD 2, PD 3). The grade 3 toxicities of neutropenia (6%) and thrombocytopenia (6%) were observed. Median overall and progression-survival times (all patients) were 9.8 and 6.2 months, respectively. Conclusions: Arterial infusion 5-FU 1,000mg/m2 combined with full-dose systemic gemcitabine was tolerable and can produce a high response rate with encouraging survival duration for unresectable pancreatic cancer. No significant financial relationships to disclose.

Phase I/II study of transcatheter arterial chemoembolization with cisplatin powder and degradable starch microspheres for unresectable hepatic metastases from colorectal cancer refractory to systemic standard chemotherapy.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 577-577
Author(s):  
H. Nishiofuku ◽  
T. Tanaka ◽  
H. Anai ◽  
S. Sueyoshi ◽  
M. Matsuoka ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Tumor Response ◽  
Transcatheter Arterial Chemoembolization ◽  
Response Rate ◽  
Survival Duration ◽  
Transaminase Elevation ◽  
Degradable Starch Microspheres ◽  
Cisplatin Powder ◽  
Arterial Chemoembolization

577 Background: We conducted a phase I/II study of novel transcatheter arterial chemoembolization with cisplatin powder and degradable starch microspheres (DSM) to determine the recommended dose (RD) and to assess the efficacy and safety. Methods: Cisplatin powder and DSM mixing solution was administered followed by the injection of DSM alone via hepatic artery every 4 weeks. In phase I, cohorts of 3 patients received escalating dose of cisplatin (50, 65 and 80mg/m2), and RD was estimated during the first cycle. In the phase II, more RD patients were added to assess tumor response, toxicity, hepatic progression free survival (H-PFS) and 6-month overall survival (OS) rate. Results: A total of 24 patients (male 16, female 8; mean age 63.0, range 45-79; colon 15, rectal 9) were enrolled in this study. FOLFOX had previously been administered to all patients, irinotecan-containing regimen to 12 and bevacizumab and/or cetuximab to 14. During phase I (n= 9 patients), maximum tolerated dose was not reached and cisplatin 80 mg/m2 was recommended for a phase II. Phase II enrolled 15 patients. The following grade 3 toxicities were observed: platelets reduction 16.6%, aspartate transaminase elevation 38.8%, alanine transaminase elevation 16.6%, hyponatremia 11.1%, cholecystitis 5.5%. The tumor response rate was 53.3% (CR 0, PR 8, SD 6, and PD 1). The median H-PFS was 6.3 months (95% CI; 2.71 to 9.88) and 6 -month OS rate was 86.7%. Conclusions: This phase I/II study demonstrates that novel transcatheter arterial chemoembolization with 80 mg/m2 cisplatin powder and DSM is well tolerable, and can produce a high response rate with encouraging survival duration. Further clinical trials are warranted. No significant financial relationships to disclose.

Phase II/III clinical trial with VEGFR2-epitope peptide and gemcitabine for patients with locally advanced, metastatic, or unresectable pancreatic cancer: Pegasus-PC study.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 223-223 ◽  
Author(s):  
Hiroki Yamaue ◽  
Masaji Tani ◽  
Motoki Miyazawa ◽  
Kenji Yamao ◽  
Nobumasa Mizuno ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Phase I ◽  
Sample Size ◽  
Survival Time ◽  
Phase Ii ◽  
Locally Advanced ◽  
Type I ◽  
Unresectable Pancreatic Cancer ◽  
Epitope Peptide

223 Background: Gemcitabine is a key drug for treating pancreatic cancer; however, with the limitation in clinical benefits, the development of another potent therapeutic was strongly called for. VEGF-receptor 2 (VEGFR2: Flk-1 and KDR) is an essential target for tumor angiogenesis, and we have executed a phase I clinical trial using gemcitabine and VEGFR2-peptide (Cancer Sci 2010). Based on promising phase I trial results, a multicenter, randomized, placebo-controlled, double-blind phase II/III clinical trial has been conducted (UMIN000001664). Methods: The eligibility criteria are: locally advanced, metastatic, or unresectable pancreatic cancer. Patients were allocated to either VEGFR2 peptide (OTS102) + gemcitabine group or placebo + gemcitabine in 2:1 ratio by dynamic allocation method. The primary endpoint was overall survival. The Harrington-Fleming test, with the weight proportional to cumulative death probability, was used for the statistical analysis under the time-lagged effect of immunotherapy. Sample size was estimated presuming the effects will be observed from the time point of 50% cumulative survival rate. Assuming a type I error alpha (two-sided) level of 5% and a power of 80% or more for 50%-60% reduction of hazard, sample size necessary was estimated as 100 patients for the active group and 50 patients for the placebo group. Results: No statistically significant survival time prolongation was observed in OTS102 add-on group (p = 0.92). However, the three-month landmark analysis revealed significant interaction between the treatment and reports of indurations or ulcerations (p = 0.005) in add-on group, and if patients survived for over three months, grade 1-2 patients had better survival than grade 0 (1-year survival: 47%(23/49) and 22%(9/44), respectively) in add-on group. Conclusions: Despite the lack of survival time prolongation by OTS102 add-on to gemcitabine therapy, patients experienced injection site indurations or ulcerations may have better survival, suggesting new prognostic factors for VEGFR2-epitope peptide. Our results indicate the possibility of epitope peptide used in cocktail therapies. Clinical trial information: UMIN000001664.

Second-line chemotherapy by FOLFIRINOX with unresectable pancreatic cancer (phase I, II study).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 297-297 ◽  
Author(s):  
Noritoshi Kobayashi ◽  
Motohiko Tokuhisa ◽  
Ayumu Goto ◽  
Itaru Endo ◽  
Yasushi Ichikawa
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Continuous Infusion ◽  
Phase Ii ◽  
Recommended Dose ◽  
Unresectable Pancreatic Cancer ◽  
Second Line ◽  
Second Line Chemotherapy ◽  
Level 1 ◽  
Line Chemotherapy

297 Background: The purpose of this study was to determine the maximum tolerated dose (MTD), dose limiting toxicities (DLT), and efficacy of the second-line chemotherapy (after gemcitabine based chemotherapy) by FOLFIRINOX with unresectable pancreatic cancer. Methods: The subjects were histopathologically proven unresectable pancreatic cancer patients. The schedule was oxaliplatin 85mg/m2 on day1, irinotecan on day1, leucovorin 400mg/m2 on day 1 followed by FU 400mg/m2 as a bolus on day 1 and 2400mg/m2 as 46-hour continuous infusion biweekly. We were planned the dose of oxaliplatin, leucovorin and FU were fixed and the dose of irinotecan was defined as follows: level 0: 100mg/m2, level 1: 125mg/m2, level 2: 150mg/m2, and level 3: 180mg/m2. We started level 1 and at least three patients were enrolled at same dose two cycles. If DLT was observed two patients in six or three patients, we suspected the level was MTD. We also evaluated this study as phase II. Primary end point was response rate (RR). We also evaluated progression free survival (PFS), overall survival (OS) and adverse event (AE). Results: Eighteen patients were enrolled in this study (man: n = 11, woman: n = 7). We evaluated initial eight patients as phase I study. One patient had neutropenia and another one patient had hyperglycemia and severe infection. We decided level 1 was MTD and recommended dose was level 0. According to phase II study, RR was 22.2% (CR: n = 0, PR: n = 4, SD: n = 7, PD: n = 7) and disease control rate (DCR) was 61.1%. PFS was 2.8 (0.7-11.7) months and OS was 9.8 (2.4-14.4) months. The most common severe AE was neutropenia (66.7%). Fibril neutropenia was occurred one (5.6%) case. Conclusions: Recommended dose was oxaliplatin 85mg/m2 on day1, irinotecan 100mg/m2 on day1, leucovorin 400mg/m2 on day 1 followed by FU 400mg/m2 as a bolus on day 1 and 2400mg/m2 as 46-hour continuous infusion. RR was 22.2% and major AE was neutropenia but FN was rare. Second-line FOLFIRINOX is marginally effective treatment for gemcitabine-base chemotherapy failure cases.

Update result of HGCSG 1403: Phase I trial of oxaliplatin/irinotecan/S-1 (OX-IRIS) as first-line chemotherapy for unresectable pancreatic cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 359-359
Author(s):  
Shintaro Nakano ◽  
Yasuyuki Kawamoto ◽  
Satoshi Yuki ◽  
Masataka Yagisawa ◽  
Kentaro Sawada ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Standard Treatment ◽  
Response Rate ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Unresectable Pancreatic Cancer ◽  
Level 1 ◽  
Ecog Ps

359 Background: FOLFIRINOX has become one of the standard treatment for unresectable pancreatic cancer with distant metastasis. OX-IRIS is the combination therapy of oxaliplatin (L-OHP), irinotecan (IRI) and S-1. It is the useful treatment to dispense with a continuous infusion of 5FU by administering S-1 orally. For establishing OX-IRIS therapy as a new standard treatment, we planned this study for evaluating dose limiting toxicity (DLT) and maximum tolerated dose (MTD). Methods: This study was carried out as a multicenter phase I study. Chemotherapy-naïve patients with unresectable pancreatic cancer were included. L-OHP and IRI were administered on day 1 and 15, and S-1 was taken twice a day in day 1-14, and then 14 days were rest for 1 cycle. The primary endpoints were the frequency of DLT and estimating of MTD. Secondary endpoints were safety, response rate, progression-free survival (PFS) and overall survival (OS). Results: Between January 2016 and August 2017, 13 cases were enrolled. The patients’ backgrounds were median age 62; male /female, 9/4; the primary tumor sites head /body and tail, 8/5; ECOG PS 0/1, 7/6; UR-LA /UR-M, 4/9. Two of five enrolled in level 0 (L-OHP: 85 mg/m2, IRI: 100 mg/m2, S-1: 80 mg/m2) had DLT. One of six in level -1 (L-OHP: 65 mg/m2, IRI: 100 mg/m2, S-1: 80 mg/m2) had DLT. At level 0, 100% of cases had anemia and fatigue, 80% anorexia, diarrhea, peripheral sensory neuropathy, 60% platelet count decrease. At level -1, 100% had anemia, 75% nausea and fatigue, 63% anorexia. Response rate was 10% and disease control rate was 70% in ten cases with evaluable lesion. Median PFS was 4.1 months (95%C.I.; 0.0-8.6 months). Median OS was 13.7 months (95%C.I.; 5.9-21.5 months). Conclusions: In this study, MTD was estimated to be level 0, and determined recommended dose is level -1 for the planned future study. We are going to evaluate efficacy and safety in a phase II study. (UMIN ID: 000017002) Clinical trial information: 000017002.

Randomized phase II study of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel combination therapy for locally advanced pancreatic cancer (JCOG1407).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4017-4017
Author(s):  
Masato Ozaka ◽  
Makoto Ueno ◽  
Hiroshi Ishii ◽  
Junki Mizusawa ◽  
Hiroshi Katayama ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Response Rate ◽  
Controlled Trial ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer ◽  
Free Survival ◽  
Randomized Phase Ii

4017 Background: FOLFIRINOX, consisting of leucovorin (LV), fluorouracil (FU), irinotecan (IRI) and oxaliplatin (L-OHP), and GnP, consisting of gemcitabine (GEM) plus nab-paclitaxel (nPTX), have shown superior efficacy over GEM in patients (pts) with metastatic pancreatic cancer. Although several studies have reported the efficacy of FOLFIRINOX or GnP for pts with locally advanced pancreatic cancer (LAPC), no randomized controlled trial to compare the two regimens has been conducted in those pts. To select the most promising chemotherapy for LAPC, a randomized phase II selection design trial (JCOG1407) was conducted to compare between modified FOLFIRINOX (FOLFIRINOX with dose reduction of IRI and without bolus FU; Arm A) and GnP (Arm B) for pts with LAPC. Methods: In Arm A, 85 mg/m2 of L-OHP, 200 mg/m2 of l-LV, 150 mg/m2 of IRI, followed by 2,400 mg/m2 of continuous FU over 46 hours are infused every 2 weeks. In Arm B, 125 mg/m2 of nPTX followed by 1,000 mg/m2 of GEM are infused on days 1, 8, and 15 every 4 weeks. The primary endpoint was overall survival (the proportion of 1-year OS), and secondary endpoints included progression-free survival (PFS), distant metastasis-free survival (MFS) and response rate in pts with target lesions. The planned sample size was 124 pts to select more effective regimen in 1-year OS with a probability of at least 0.85 and to test the null hypothesis of 53% in 1-year OS with a one-sided alpha of 5% and 80% Results: From 2015 to 2019, a total of 126 pts was enrolled from 29 Japanese institutions, and were allocated to Arm A (n = 62) or Arm B (n = 64). The median (range) age was 66 (44-75) years and 58.7% were male. At the analysis, after a median (range) follow-up of 1.52 (0.55-3.99) years, 75 (59.5%) pts died. The proportion of 1-year OS was better in Arm B, 77.4% [95% CI 64.9–86.0] vs. 82.5% [95% CI 70.7–89.9], but 2-year OS was better in Arm A, 48.2% [95% CI 33.3–61.7] vs. 39.7% [95% CI 28.6–52.5]. Median OS was 2.0 years [95% CI 1.6-2.7] in Arm A and 1.8 years [95% CI 1.5-2.0] in Arm B. 1-year PFS for Arm A/B was 47.5 % [95% CI 34.5-59.4]/40.2% [95% CI 27.8-52.3], and 1-year MFS was 64.2 % [95% CI 50.9-74.8]/57.3% [95% CI 43.9-68.6]. Arm A was better OS in pts with CA19-9 <1000 U/mL and the opposite trend was observed in pts with CA19-9>1000 U/mL. Response rate was 30.9% [95% CI 19.1-44.8] in Arm A, and 41.4% [95% CI 28.6-55.1]) in Arm B. Incidences of grade 3-4 non-hematological toxicities for Arm A and Arm B were 66.1% and 67.2%, respectively. There was no treatment-related death. Conclusions: This study was the first randomized trial comparing the two regimens. The 1-year OS of the primary endpoint in GnP was better than mFOLFIRINOX, but mFOLFIRINOX achieved longer survival in 2-year OS. It is required to confirm longer OS and safety profiles which regimen should be selected as a standard regimen in LAPC. Clinical trial information: jRCTs031180085.

scholarly journals HGCSG1403: Phase I trial of oxaliplatin/irinotecan/S-1 (OX-IRIS) as first-line chemotherapy for unresectable pancreatic cancer

2018 ◽  
Vol 29 ◽  
pp. ix62
Author(s):  
A. Yoshikawa ◽  
Y. Kawamoto ◽  
S. Yuki ◽  
S. Nakano ◽  
K. Sawada ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Phase I Trial ◽  
Unresectable Pancreatic Cancer ◽  
First Line ◽  
Line Chemotherapy

Cancer Research Campaign phase II trial of temozolomide in metastatic melanoma.

1995 ◽  
Vol 13 (4) ◽  
pp. 910-913 ◽  
Author(s):  
N M Bleehen ◽  
E S Newlands ◽  
S M Lee ◽  
N Thatcher ◽  
P Selby ◽  
...  
Keyword(s):  
Phase I ◽  
Total Dose ◽  
Metastatic Melanoma ◽  
Median Survival ◽  
Phase Ii ◽  
Lung Metastases ◽  
Interleukin 2 ◽  
Survival Duration ◽  
Median Response ◽  
Median Survival Duration

PURPOSE Sixty patients with metastatic melanoma were treated in a phase II study with the imidazotetrazine derivative temozolamide to assess further the efficacy demonstrated in previous phase I studies. PATIENTS AND METHODS Fifty-five of 56 eligible patients were assessable for toxicity and 49 for response. The patients received temozolomide 150 mg/m2/d over 5 successive days orally (total dose, 750 mg/m2) in the first course. Courses were repeated every 4 weeks and the dose was escalated to 200 mg/m2/d x 5 (total dose, 1 g/m2) after the first course if toxicity was acceptable. Patients were all chemotherapy-naive, except for two who had previously received interferon alfa and one who had received interleukin-2 (the latter patient had also received two phase I drugs some time previously). RESULTS A complete response (CR) was documented in three patients (all with lung metastases) and a partial response (PR) in nine patients (21% CR plus PR rate). Seven of 56 patients were not assessable for response because of early death or deterioration. The overall response rate excluding these patients is 12 of 49 (24%). The median response duration was 6 months (range, 2.5 to 22+). Toxicity of the regimen, which was mainly hematopoietic, was low. The median survival duration for all patients was 5.5 months (range, 0.5 to 29.5). For responders, the median survival duration was 14.5 months (range, 3 to 28+), with four patients still alive. CONCLUSION Temozolomide in the schedule used has as good activity in chemotherapy-naive metastatic melanoma as the other most active agents currently in use. Further studies of the drug on its own and in combination with other agents is recommended.

Phase II trial of hepatic arterial infusion of fluorouracil and recombinant human interferon alfa-2b for liver metastases of colorectal cancer refractory to systemic fluorouracil and leucovorin.

1997 ◽  
Vol 15 (4) ◽  
pp. 1432-1438 ◽  
Author(s):  
Y Z Patt ◽  
A Hoque ◽  
R Lozano ◽  
R Pozdur ◽  
J Chase ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Response Rate ◽  
Liver Tumors ◽  
Hepatic Arterial Infusion ◽  
Interferon Alfa ◽  
Survival Duration ◽  
Common Side Effect ◽  
Human Interferon ◽  
Arterial Infusion ◽  
Median Response

PURPOSE To determine the toxicity, response rate, and survival in patients treated with hepatic arterial infusion (HAI) of fluorouracil (5-FU) plus recombinant human interferon alfa-2b (rIFN-alpha 2b) (Intron-A; Schering-Plough, Inc, Kenilworth, NJ) for colorectal carcinoma (CRC) liver metastases refractory to systemic 5-FU plus leucovorin (LCV). PATIENTS AND METHODS Forty-eight patients were given a 6-hour HAI of rIFN-alpha 2b 5 MU/m2 followed by an 18-hour HAI of 5-FU, 1,500 mg/m2 daily for 5 days. Twenty-nine patients were treated through percutaneously placed catheters and 19 through implantable infusion pumps (Shiley Infusaid Inc, Noorwood, MA). Treatment cycles were repeated every 28 to 35 days. RESULTS There were three (6.6%) complete remissions (CRs) and 12 (26.6%) partial remissions (PRs), for a CR plus PR rate of 33.3% among 45 assessable patients (95% confidence interval [CI], 20% to 49%). The median response duration was 7 months, while median survival duration was 15 months. Grade 3 to 4 treatment-related toxic effects included mucositis (40%), neutropenia (42%), and thrombocytopenia (12%). No hepatobiliary toxicity was encountered in any of the patients. Treatment was discontinued because of progressive liver disease in 23 patients and extrahepatic progression in 16, while six patients continue treatment through an infusaid pump. CONCLUSION HAI of 5-FU plus rIFN-alpha 2b is well tolerated, devoid of hepatobiliary toxicity, and can produce a response rate of 33.3% among patients refractory to bolus intravenous (IV) 5-FU plus LCV. The lack of hepatobiliary toxicity may permit salvage HAI with floxuridine (FUDR) in patients whose liver tumors fail to respond to HAI of 5-FU plus rIFN-alpha 2b. Because diarrhea was not a common side effect of HAI of 5-FU plus rIFN-alpha 2b, it would be of interest to investigate whether alternating HAI of 5-FU and rIFN-alpha 2b with systemic irinotecan (CPT-11) will decrease the incidence of both hepatic and extrahepatic disease progression.

scholarly journals HGCSG 1403: phase I trial of oxaliplatin /irinotecan /S-1 (OX-IRIS) for unresectable pancreatic cancer

2018 ◽  
Vol 29 ◽  
pp. vii63
Author(s):  
Yasuyuki Kawamoto ◽  
Satoshi Yuki ◽  
Hideyuki Hayashi ◽  
Shintaro Nakano ◽  
Kentaro Sawada ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Phase I Trial ◽  
Unresectable Pancreatic Cancer
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