A phase II multicentric trial of combined chemotherapy with gemcitabine plus S-1 in patients with advanced pancreatic cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15129-15129
Author(s):  
S. Ohkawa ◽  
A. Amano ◽  
M. Ueno ◽  
K. Miyakawa ◽  
K. Sugimori ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Survival Time ◽  
Median Survival ◽  
Phase Ii ◽  
Median Survival Time ◽  
Progressive Disease ◽  
Advanced Pancreatic Cancer ◽  
Combined Chemotherapy ◽  
Standard Drug

15129 Background: While gemcitabine (GEM) is the standard drug for chemotherapy against advanced pancreatic cancer, the development of multidrug therapies for improved outcome is important. We conducted multicentric combined chemotherapy with GEM and S-1 trial and reported the results of the phase I trial last year. And this phase II study evaluated the efficacy and feasibility. Methods: The subjects had unresectable pancreatic ductal cancer. Eligibility criteria were pathologically-proven, Karnofsky performance status 80 to 100%, age 20 to 74 years, adequate hematological, renal, and liver functions and written informed consent. The method of administration was single administration of GEM on the first day of the week 1000 mg/m2, with concurrent administration of S-1 at 80 (<1.5 m2) to 100 (=1.5 m2) mg/day × 7 days, repeated every other week until the progressive disease or life threatening adverse events. This administration dose was determined from the result of the phase I study. The primary endpoint was median survival time. And the secondary endpoints were the overall response rate and the toxicities. Results: 40 patients(pts) were enrolled. Average age was 62.9±8.3 years (34–73 years). Thirty nine pts were conducted this therapy except one who refused this study before the start of administration. Thirty eight pts were evaluable for response, partial response, stable disease, progressive disease were observed in 7 (17.5%), 21 (52.5%) and 10 pts (25.0%), respectively. The median survival time at this stage is 276±51 days in this ongoing study. Grade 3 and 4 toxicities were mainly leucocytes(10 pts), neutrophils(8 pts) and anorexia(6 pts). Conclusions: The GEM plus S-1 combined chemotherapy is effective and feasible in patients with advanced pancreatic cancer. No significant financial relationships to disclose.

A phase I multicentric trial of combined chemotherapy with gemcitabine plus S-1 in patients with advanced pancreatic cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14047-14047
Author(s):  
S. Ohkawa ◽  
A. Amano ◽  
M. Ueno ◽  
K. Miyakawa ◽  
K. Sugimori ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Phase I Trial ◽  
Advanced Pancreatic Cancer ◽  
Optimal Dose ◽  
Maximum Tolerated Dose ◽  
Combined Chemotherapy ◽  
Concurrent Administration ◽  
Standard Drug ◽  
Level 3

14047 Background: While gemcitabine (GEM) is the standard drug for chemotherapy against advanced pancreatic cancer, the development of multidrug therapies for improved outcome is important. We conducted multicentric combined chemotherapy with GEM and S-1 and report the results of the phase I trial. Methods: The subjects had unresectable pancreatic ductal cancer. The method of administration was single administration of GEM on the first day of the week from Level 1 to Level 4 at 400 to 1000 mg/m2, with concurrent administration of S-1 at 40 to 100 mg/day × 7 days, repeated every other week as a collaborative trial conducted at 3 facilities. The purpose was to determine the optimal dose with adverse events as an indicator. Results: Eighteen patients were enrolled (3 each at Levels 1, 2, 3 and 4’, 6 at Level 4). Average age was 60.9 years (38 - 71 years). There was no dose limiting toxicity (DLT) up to Level 3. Level 4 was the maximum tolerated dose since DLT was observed in 4/6 patients (mucositis 2, rash 1, anorexia 1), and no DLT was observed in 3 additional patients at Level 4’. The resulting recommended dose was Level 4 (GEM 1000 mg/m2, S-1 100 mg/day). For reference, partial response was observed in 5 patients, and median survival time at this stage is 336±39 days. Conclusions: The recommended dosage of GEM + S-1 combined chemotherapy for unresectable advanced pancreatic cancer was determined in a phase I trial. We intend to proceed to a phase II trial. No significant financial relationships to disclose.

Multi-Institutional Phase I/II Trial of Oral Bexarotene in Combination With Cisplatin and Vinorelbine in Previously Untreated Patients With Advanced Non–Small-Cell Lung Cancer

2001 ◽  
Vol 19 (10) ◽  
pp. 2626-2637 ◽  
Author(s):  
Fadlo R. Khuri ◽  
James R. Rigas ◽  
Robert A. Figlin ◽  
Richard J. Gralla ◽  
Dong M. Shin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase I ◽  
Survival Time ◽  
Median Survival ◽  
Phase Ii ◽  
Median Survival Time ◽  
Survival Rates ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE: Bexarotene (Targretin; Ligand Pharmaceuticals, Inc, San Diego, CA) is a retinoid-X-receptor (RXR)-selective retinoid with preclinical antitumor activity in squamous cell cancers. In this phase I/II trial, we combined bexarotene with cisplatin and vinorelbine in the treatment of patients with non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-three patients who had stage IIIB NSCLC with pleural effusion or stage IV NSCLC and had received no prior therapy received bexarotene in combination with cisplatin (100 mg/m2) and vinorelbine (alternating doses of 30 mg/m2 and 15 mg/m2). In the phase I portion, the daily dose of bexarotene was escalated in cohorts of three patients from 150 mg/m2 to 600 mg/m2, beginning 1 week before the start of the cisplatin-vinorelbine regimen. Once the maximum-tolerated dose (MTD) of bexarotene was determined, the study entered the phase II portion. Response rate was the primary end point; median survival time and 1-year survival rate were secondary end points. RESULTS: In the phase I portion, the daily MTD of bexarotene was determined to be 400 mg/m2. Eight of 43 patients exhibited major responses. Seven (25%) of the 28 patients in the phase II portion responded to treatment. The median survival time in the phase II portion was 14 months; nine (32%) of the 28 patients were still alive at a minimum follow-up of 2 years. One-year and projected 3-year survival rates were 61% and 30%, respectively. The most common grade 3 and 4 adverse events were hyperlipemia, leukopenia, nausea, vomiting, pneumonia, dyspnea, anemia, and asthenia. Grade 3 and 4 laboratory abnormalities with incidences greater than 5% were decreased hemoglobin levels and WBC, absolute neutrophil, and absolute lymphocyte counts and increased prothrombin time and creatinine and amylase levels. Of the two cases of pancreatitis, one required hospitalization and both were associated with increased triglyceride levels. There was one death secondary to renal insufficiency unrelated to bexarotene treatment. CONCLUSION: In patients with advanced NSCLC, bexarotene with cisplatin and vinorelbine yielded acceptable phase II response rates (25%) and was associated with better-than-expected survival (14-month median survival time; 61% 1-year, 32% 2-year, and 30% projected 3-year survival rates). The regimen should be studied in larger clinical trials.

scholarly journals Bioelectrical impedance phase angle as a prognostic indicator in advanced pancreatic cancer

2004 ◽  
Vol 92 (6) ◽  
pp. 957-962 ◽  
Author(s):  
Digant Gupta ◽  
Christopher G. Lis ◽  
Sadie L. Dahlk ◽  
Pankaj G. Vashi ◽  
James F. Grutsch ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Survival Time ◽  
Median Survival ◽  
Phase Angle ◽  
Median Survival Time ◽  
Prognostic Significance ◽  
Advanced Pancreatic Cancer ◽  
Case Series ◽  
Bioelectrical Impedance ◽  
Prognostic Indicator

Bioelectrical impedance analysis (BIA) is an easy-to-use, non-invasive and reproducible technique to evaluate changes in body composition and nutritional status. Phase angle, determined by BIA, has been found to be a prognostic indicator in several chronic conditions, such as HIV, liver cirrhosis, chronic obstructive pulmonary disease and lung cancer, and in patients undergoing dialysis. The present study investigated the prognostic role of phase angle in advanced pancreatic cancer. We evaluated a case series of fifty-eight stage IV pancreatic cancer patients treated at Cancer Treatment Centers of America® at Midwestern Regional Medical Center (Zion, IL, USA) between January 2000 and July 2003. BIA was conducted on all patients using a bioelectrical impedance analyser that operated at 50kHz. The phase angle was calculated as capacitance (Xc)/resistance (R) and expressed in degrees. The Kaplan–Meier method was used to calculate survival. Cox proportional hazard models were constructed to evaluate the prognostic effect of phase angle independent of other clinical and nutritional variables. The correlations between phase angle and traditional nutritional measures were evaluated using Pearson and Spearman coefficients. Patients with phase angle <5·0° had a median survival time of 6·3 (95% CI 3·5, 9·2) months (n 29), while those with phase angle >5·0° had a median survival time of 10·2 (95% CI 9·6, 10·8) months (n 29); this difference was statistically significant (P=0·02). The present study demonstrates that phase angle is a strong prognostic indicator in advanced pancreatic cancer. Similar studies in other cancer settings with larger sample sizes are needed to further validate the prognostic significance of the phase angle.

Phase II study with the combination etoposide, doxorubicin, and cisplatin in advanced measurable gastric cancer.

1989 ◽  
Vol 7 (9) ◽  
pp. 1310-1317 ◽  
Author(s):  
P Preusser ◽  
H Wilke ◽  
W Achterrath ◽  
U Fink ◽  
L Lenaz ◽  
...  
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Phase Ii ◽  
Metastatic Disease ◽  
Median Survival Time ◽  
Response Rate ◽  
Response Duration ◽  
World Health ◽  
Who Grade ◽  
Median Response

In this phase II multicenter trial, 67 evaluable patients with advanced measurable gastric carcinoma were treated with a combination of etoposide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (EAP). The overall response rate was 64%, including 21% complete responses (CRs). In 55 patients with metastatic disease, 31 responses (51%) including eight CRs (15%) were achieved. Responses were seen in all metastatic sites, but the response rate was lower in patients with peritoneal carcinomatosis. In 12 patients with locoregional disease, six CRs and six partial responses (PRs) were observed. Eight CRs (three and five in patients with metastatic and locoregional disease, respectively) were pathologically confirmed. The overall median response duration was 7 months; it was 16 months for patients achieving CR (22 months for pathologically confirmed CR [pCR]), and 6 months for PR. The median survival time for all patients was 9 months, for the patients who achieved CR 17 months, for pCR 23 months, and for PR 9.5 months. Median survival time for all patients with metastatic disease was 8 months, and for locoregional disease 12.5 months. Six patients (9%) (four local, two metastatic disease) were alive at 2 years, and four patients are alive and disease free at 35+ to 56+ months. Main toxicities were leukopenia and thrombocytopenia, with 64% of patients developing grade 3 to 4 myelosuppression and 12% severe infections. Nonhematologic toxicities of World Health Organization (WHO) grade 4 were not observed.

Phase II trial of irinotecan/docetaxel for advanced pancreatic cancer with randomization between irinotecan/docetaxel and irinotecan/docetaxel plus C225, a monoclonal antibody to the epidermal growth factor receptor (EGF-r) : Eastern Cooperative Oncology

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4519-4519 ◽  
Author(s):  
B. A. Burtness ◽  
M. Powell ◽  
J. Berlin ◽  
D. Liles ◽  
A. Chapman ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Median Survival ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Advanced Pancreatic Cancer ◽  
Growth Factor Receptor ◽  
Distant Metastases ◽  
Median Number ◽  
Number Of Cycles ◽  
Ecog Ps

4519 Background: Gemcitabine (G) is standard for metastatic pancreatic cancer (PC), with median survivals of 6 months (m). Second cytotoxic or biologic agents do not substantially advance survival. EGFR is expressed on PC and a phase II trial of G plus cetuximab (C) resulted in favorable 1 year survival. A phase II trial of irinotecan/docetaxel (I/D) chemotherapy reported a median survival for metastatic patients (pts) of 9 m. We conducted this randomized phase II trial to confirm the activity of this non-G regimen, and determine whether combining it with C was feasible and active. The primary endpoint was response. Methods: Pts required histologic confirmation of adenocarcinoma of the pancreas, evidence of distant metastases, ECOG PS 0–1, normal bilirubin, written informed consent, and were randomly assigned to Arm A (N=47) or B (N=45). Imaging with CT or MR within 4 weeks (wk) was used for tumor measurement. Dexamethasone was given 12 hours (h), 1 h before and 12 h after chemotherapy. Pts on Arm A received D 35 mg/m2 over 1 h and I 35 mg/m2 over 30 minutes weekly x 4 in a 6 wk cycle. Pts on Arm B received the same therapy, but C (loading dose 400 mg/m2 wk 1, 250 mg/m2 weekly thereafter) was given before D. Pts not receiving therapeutic anticoagulation received enoxaparin 40 mg per day. Pts were restaged (RECIST) after 2 cycles. Results: Median age Arm A: 59.9, Arm B: 60.2 years. Arm A 55% male, 32% PS 0, 97% EGFR immuno+. Arm B 84% male, 42% PS 0, 97% EGFR +. Median number of cycles for each arm 2 (1 -10). >4 cycles were delivered to 10.5% of pts Arm A, 20.9% Arm B. Grade ¾ neutropenia 26% Arm A, 33% Arm B. Grade 3 nausea 28% Arm A, 18% Arm B; Grade ¾ diarrhea 33% Arm A, 44.4% Arm B. 1 treatment-related death per arm. Median overall survival (OS), with 70.2% of pts known to have died, 6.5m [(95% CI (4.8, 8.6)] in Arm A. With 86.7% of pts known to have died in Arm B, OS 7.4 m [95% CI (4.4, 10.7)]. Response/progression data will be available at time of presentation. Conclusions: Weekly I/D ± C is associated with high rates of grade ¾ neutropenia/diarrhea. Median survival is 6.5m for I/D and 7.4m for I/D/C. Non-G containing therapy is active in metastatic PC. [Table: see text]

Phase I/II trial of gemcitabine (Gem) plus irinotecan (CPT-11) for metastatic pancreatic cancer (MPC).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 301-301
Author(s):  
Takuo Yamai ◽  
Tatsuya Ioka ◽  
Hironari Sueyoshi ◽  
Ryoji Takada ◽  
Nobuyasu Fukutake ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Phase I ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Phase I Study ◽  
Progressive Disease ◽  
Metastatic Pancreatic Cancer ◽  
Refractory Ascites ◽  
Recommended Phase Ii Dose

301 Background: Treatment options for patients with metastatic pancreatic cancer are still limited. Recently, new strategies to prolong disease control are reported. We conducted phase I/II trial of GEM+CPT-11 combination chemotherapy for MPC to evaluate the effectiveness and safety. Methods: As phase I study, traditional 3 + 3 dose-escalation design was used to determine the maximum tolerated dose (MTD) and the recommended phase II dose. Four escalating dose levels of GEM/CPT-11 (800/60 mg/m2, 1000/60 mg/m2, 1000/80 mg/m2, and 1000/100 mg/m2) were studied. As results of this investigation, the recommended phase II dose was GEM 1000 mg/m2 and CPT-11 100 mg/m2, biweekly. Phase II eligibility included naïve MPC, PS0-2, Pathological diagnosis, no refractory ascites and pleural effusion, and adequate organ function. Primary endpoint was overall survival. Results: Eighteen patients were entered phase I study. The DLTs were anorexia, and nausea/vomiting. Severe neutropenia was rare. MTDs were determined GEM 1000 and CPT-11 100 mg/m2. After that, we investigated phase II trial in 40 patients. There were 6 partial response, 14 stable disease, 18 progressive disease and 2 in-evaluable. Response rate was 16%. The median overall survival was 7.5 months; progressive disease 4.0 months. Grade 3 to 4 toxicity included neutropenia (7%), anemia (7%), diarrhea (7%), ALT elevation (10%), pneumonitis(7%). There was no treatment-related death. Conclusions: This combination chemotherapy is not effective as first-line chemotherapy for metastatic pancreatic cancer. But this is safe and generally well tolerated. This chemotherapy could be effective of salvage chemotherapy with low toxicity after standard chemotherapy such as FOLFIRINOX.

FOLFIRINOX for patients with borderline and never-resectable locally advanced pancreatic cancer, with the addition of chemoradiotherapy for potentially resectable patients: A phase II study.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 408-408
Author(s):  
Jon Kroll Bjerregaard ◽  
Morten Ladekarl ◽  
Anna-Lene Fromm ◽  
Per Pfeiffer
Keyword(s):  
Pancreatic Cancer ◽  
Median Survival ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Observation Time ◽  
Stage Ii ◽  
Locally Advanced Pancreatic Cancer

408 Background: Locally advanced pancreatic cancer (LAPC) is often a mix of borderline and never-resectable tumors. Multimodality treatment might downstage these tumors to allow a potential radical resection, especially the borderline group. In this ongoing phase II study we examined the feasibility of FOLFIRINOX with or without CRT followed by surgery for both borderline and never-resectable tumors (NCT-01397019). Methods: Patients in performance status 0-1, with initially non-resectable stage II/III pancreatic cancer were offered FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, 5FU 400 mg/m2+ 2400 mg/m2) every 14 days. Every 4th series the patients were evaluated and offered CRT (50.4 Gy/27F & capecitabine) if deemed potentially resectable. Resections were performed if deemed possible by the MDT. Results: Between August 2012 and present, 58 patients have been recruited with a median observation time of 14.5 months. Median age was 65(range 38-75) years, with 47%/53% stage II/III distribution. Median CA19-9 was 299(range 2-13,432). Two-hundred-seventy-four courses of FOLFIRINOX have been given, with a median of 6.5 per patient, with a median of 2 without dose modifications. Presently twenty-one patients have been treated with CRT. Twelve patients have been resected, of which 7 received prior CRT. Median survival for all patients was 15.6 months (11-NR) with a 1-year survival of 70% (49-84). For patients not resected the median survival was 12.8 months (9-16) for resected the median survival has not yet been reached. The FOLFIRINOX was associated with adverse events similar to what is expected in metastatic patients. Conclusions: FOLFIRINOX with or without CRT in patients with LAPC shows promising efficacy in patients with both borderline and never-resectable tumors. Unmodified FOLFIRINOX had acceptable toxicity, however dose reductions are often needed. CRT following initial FOLFIRINOX was feasible and without unexpected toxicity. Clinical trial information: NCT-01397019.

A phase I study of axitinib (AG-013736), a potent inhibitor of VEGFRs, in combination with gemcitabine (GEM) in patients (pts) with advanced pancreatic cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13092-13092 ◽  
Author(s):  
J. Spano ◽  
M. Moore ◽  
S. Kim ◽  
K. F. Liau ◽  
B. Hee ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Phase Ii ◽  
Tyrosine Kinases ◽  
Phase I Study ◽  
Phase Ii Study ◽  
Tumor Regression ◽  
Epigastric Pain ◽  
Cell Cancer ◽  
Advanced Pancreatic Cancer

13092 Background: Axitinib (AG-013736) is a novel small molecule inhibitor of the receptor tyrosine kinases with picomolar potency against VEGFR 1, 2 & 3 and nanomolar potency against PDGFR-beta and KIT. A phase I study in solid tumors identified 5 mg BID as the therapeutic dose; a phase II study in renal cell cancer demonstrated significant efficacy with a response rate (RR) of 46% (Rini et al, ASCO 2005). This study examined the safety, PK and preliminary efficacy of AG-013736 (AG) in combination with gemcitabine (GEM) as first-line therapy for advanced pancreatic cancer. Methods: A randomized phase II study was preceded by a phase I component. All patients (pts) in the phase I portion received 1000 mg/m2 GEM by 30-minute infusion on days 1, 8, and 15 followed by one week of rest from treatment. AG 5 mg p.o. BID was given beginning Cycle 1, Day 3 (C1D3). Eligible pts had no prior chemotherapy for advanced disease, ECOG 0–2, and no previous treatment with VEGF/VEGFR inhibitors, or anti-angiogenesis treatment. Full PK profiles were collected on C1D1 (GEM alone), C1D14 (steady state, AG alone), and C1D15 (GEM + AG). In the phase II trial, pts are randomized to AG or AG plus GEM beginning C1D1. Results: 8 pts were treated on the phase I portion of this trial. Toxicity: The primary Gr. 3/4 toxicity was hematologic: Gr. 4 anemia and Gr.3 thrombocytopenia in 1 pt and Gr. 3 neutropenia in 1 pt requiring a dose reduction for GEM in Cycle 3. Gr. 2 non-hematologic adverse events include pruritus (1 pt), abdominal pain (2 pts), epigastric pain (1 pt), melena (1 pt), and asthenia (2 pts). Gr. 2 hypertension was observed in 3 pts. Efficacy: Radiological assessment suggests 2 pts with partial response and 4 pts with stable disease: response assessments are ongoing. The median number of cycles is 3 [1,6]. Treatment for 4 pts is still ongoing: Cycle 6 (2 pts) and Cycle 2 (2 pts). Conclusions: This combination is safe and appears to be an effective treatment for advanced pancreatic cancer with significant tumor regression observed in 2 pts. Therapy was well tolerated with manageable toxicity. Additional investigation of AG-013736 in combination with GEM in the phase II setting for advanced pancreatic cancer is warranted. [Table: see text]

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