Gemcitabine, oxaliplatin and weekly high-dose 5-FU as a 24-hr-infusion in chemonaive patients with advanced or metastatic carcinoma of the gallbladder: Preliminary results of a multicenter phase II-study

4129 Background: Combinations of gemcitabine (GEM)/5-FU, GEM/oxaliplatin (LOHP) or 5-FU/LOHP work synergistically in pancreatic and/or colorectal malignancies, and have non-overlapping safety profiles. This phase II-study was designed to evaluate the efficacy and safety of the triple combination GEM/LOHP/5-FU in patients (pts) with advanced or metastatic carcinoma of the gallbladder. Methods: One-stage, multicentre phase II study. Eligibility criteria: chemonaive pts with histologically proven advanced, recurrent or metastatic gallbladder carcinoma (ECOG 0–1; expected survival >3 months; measurable disease; adequate renal, hepatic and bone marrow function). According to the results of our previous phase I-study (Proc ASCO 2003, # 1298), pts were treated with GEM 900mg/m2 as a 30-min infusion, followed by LOHP 65 mg/m2 (2-hr infusion) after a 30 min rest and 5-FU 1500 mg/m2 (24-hr-infusion) on d 1, 8, every 3 weeks. Planned sample size: 35 response evaluable patients. The primary endpoint was tumor response, secondary endpoints were toxicity, median survival, the one-year-survival rate, clinical benefit and quality of life. Results: At time of abstract submission, median follow-up of 35 enrolled pts is 9.8 months. Pt. characteristics: m/f: 11/24, median age 61 (range 42–81), ECOG 0/1: 24/11 (69/31%) pts, locally advanced/metastatic disease 1/32 (3/91%) pts. Analysis of tumor response is still pending. Grade III/IV (NCI-CTC) toxicities occurred in 36/3% of 191 cycles and were: leucopenia 3/1%, neutropenia 4/1%, thrombocytopenia 4/1%, anemia 2/0%, nausea 1/0%, sensory neuropathy 4/0%, asthenia 1/0%, elevated bilirubin 2/0%, AP 4/0%, or elevated SGOT/SGPT 1/0%, edema 1/0%, infection 1/0%, dyspnoe 1/1%. Median survival of all pts is 9.9 months (95% CI: 7.5–11.5), the one-year-survival-rate is 30 % (95% CI: 16–47). Conclusions: GEM/LOHP/5-FU combination therapy is tolerated well in patients with gallbladder cancer. The promising survival data has to be confirmed in a phase III study. (Supported by grants from Eli Lilly and Company, Indianapolis, IN, USA and Sanofi-Synthelabo, Paris, France). [Table: see text]

Download Full-text

A phase II study of combined 5-fluorouracil, doxorubicin, and cisplatin in the treatment of advanced upper gastrointestinal adenocarcinomas.

Journal of Clinical Oncology ◽

10.1200/jco.1986.4.7.1053 ◽

1986 ◽

Vol 4 (7) ◽

pp. 1053-1057 ◽

Cited By ~ 96

Author(s):

C G Moertel ◽

J Rubin ◽

M J O'Connell ◽

A J Schutt ◽

H S Wieand

Keyword(s):

Median Survival ◽

Phase Ii ◽

Phase Ii Study ◽

Ampulla Of Vater ◽

Phase Iii ◽

Regression Rate ◽

Intensive Course ◽

Phase Iii Studies ◽

Upper Gastrointestinal ◽

Toxic Reactions

In a phase II study of 67 patients with upper gastrointestinal carcinomas and measurable disease without previous chemotherapy, we have evaluated the combination of intensive course 5-fluorouracil (5-FU) (300 mg/m2/d for five days) doxorubicin (40 mg/m2 on day 1), and cisplatin (60 mg/m2 on day 1). Courses were repeated every 5 weeks. Among 26 patients with gastric carcinoma, a 50% regression rate was obtained with a median survival for all patients of 9 months. Among 29 patients with pancreatic carcinoma, the regression rate was 21% and the median survival was 4 months. Regressions were also observed in smaller numbers of patients with carcinomas of the gallbladder and ampulla of Vater, as well as in cholangiocellular carcinoma of the liver. Toxic reactions were usually clinically tolerable and consisted primarily of nausea, vomiting, stomatitis, diarrhea, leukopenia, and alopecia. Phase III studies are in progress to place the value of this experimental regimen into clinical perspective.

Download Full-text

A single arm, prospective multicenter phase II study FOLFIRINOX in patients with advanced and recurrent biliary tract cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.tps514 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. TPS514-TPS514 ◽

Cited By ~ 3

Author(s):

Naminatsu Takahara ◽

Hiroyuki Isayama ◽

Yousuke Nakai ◽

Tatsuya Ioka ◽

Masashi Kanai ◽

...

Keyword(s):

Disease Progression ◽

Biliary Tract ◽

Phase Ii ◽

Biliary Tract Cancer ◽

Intravenous Infusion ◽

Tumor Response ◽

Phase Ii Study ◽

Phase Iii ◽

Open Label ◽

Tract Cancer

TPS514 Background: The current standard of care for patients with advanced biliary tract cancer (BTC) is gemcitabine and cisplatin (GC) combination chemotherapy. Despite intensive researches, no trials have proved better overall survival (OS) over GC. Recently, FOLFIRINOX provided a remarkable survival benefit over gemcitabine in patients with metastatic pancreatic cancer. Given the promising results of FOLFIRI and FOLFOX in patients with advanced BTC, FOLFIRINOX can be an attractive option in patients with advanced BTC as well. Methods: This is a single-arm, open-label, multi-center phase II study to evaluate the safety and efficacy of FOLFIRINOX in patients with advanced BTC. The major inclusion criteria are as follows; unresectable or recurrent BTC, histologically or cytologically confirmed adenocarcinoma, no prior chemotherapy or radiation therapy, age of 20-75 years, an ECOG PS of 0 or 1, at least one measurable lesion, adequate hematological, liver and renal function. The major exclusion criteria are as follows; UGT genetic polymorphisms of homozygous UGT1A1*6 or *28 or heterozygous UGT1A1*6 and *28, massive pleural effusion or ascites. FOLFIRINOX consists of oxaliplatin of 85 mg/m2, irinotecan of 180 mg/m2, leucovorin of 400 mg/m2 administered by intravenous infusion and fluorouracil of 400 mg/m2 by intravenous bolus and of 2,400 mg/m2 by continuous intravenous infusion every 2 weeks. The primary outcome is progression-free survival (PFS), and the secondary outcomes are OS, tumor response and safety. PFS and OS will be calculated from the date of enrollment until the date of documentation of disease progression or death in patients without disease progression and the date of death. Tumor response will be evaluated according to the RECIST version 1.1 every 2 months. Safety will be evaluated with the CTCAE version 4.0. A total of 35 patients will be required to provide 75% power to detect an increase in median PFS from 6 months provided by standard care of GC to 10 months in patients receiving FOLFIRINOX, with a 24 months of recruitment and 18 months of follow-up. A phase III trial will be considered when this study shows the lower limit of the 80% confidence interval for PFS is longer than 6 months. Clinical trial information: UMIN000020801.

Download Full-text

Randomized phase II study of three doses of the integrin inhibitor cilengitide versus docetaxel as second-line treatment for patients (pts) with stage IV non-small cell lung cancer (NSCLC)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.8014 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 8014-8014

Author(s):

C. Manegold ◽

J. Vansteenkiste ◽

F. Cardenal ◽

W. Schütte ◽

P. Woll ◽

...

Keyword(s):

Survival Rate ◽

Tumor Progression ◽

Phase Ii ◽

Phase Ii Study ◽

Stage Iv ◽

Progression Free Survival ◽

Open Label ◽

Randomized Phase Ii ◽

Grade 3 ◽

One Year

8014 Background: Cilengitide (EMD 121974) is the most advanced compound in clinical development of a new class of oncology drugs, the integrin inhibitors. Integrins (heterodimeric transmembrane receptors) play key roles in cell interactions. Cilengitide selectively inhibits the cell-surface integrins αVβ3 and αVβ5 on activated endothelial cells during angiogenesis and on tumor cells. Methods: Multicenter, open-label, randomized, phase II study in 140 pts with relapsed stage IV NSCLC. Pts received 1 of 3 cilengitide doses (240 [n=35], 400 [n=35], or 600 [n=36] mg/m2) twice weekly or docetaxel 75 mg/m2 (n=34) once every 3-week cycle for 6 months. Responding pts could continue cilengitide for up to 1 year. Primary endpoint: progression-free survival (PFS). Results: Median age (range) was 60 (33–80) years; 94 pts were male (67%); 83% of pts had KPS ≥80%. Median PFS (95% CI) was 54 (43–64), 63 (53–66), 63 (42–67), and 67 (61–123) days for cilengitide 240, 400, 600, and docetaxel 75 mg/m2, respectively. Median OS (95% CI) was 173 (81–197), 117 (92–209), 181 (90–326), and 194 (135–298) days, respectively. One-year survival rate (95% CI) was 13% (1–24%), 13% (0–26%), 29% (12–37%), and 27% (10–43%), respectively. Survival was similar with cilengitide 600 mg/m2 and docetaxel 75 mg/m2: median OS 181 versus 194 days and 1-year survival rate (95% CI) 29% (12–37%) versus 27% (10–43%). Five docetaxel pts (15%) had a partial response. Most pts (98%) had ≥1 adverse event (AE). Most common AEs were dyspnea (33%), nausea (30%), tumor progression (29%), and cough (23%). Dyspnea and tumor progression were more common with cilengitide than with docetaxel. Grade 3/4 treatment-related AEs were more common with docetaxel (n=13, 41%) than cilengitide 240 (n=2, 6%), 400 (n=4, 11%), or 600 (n=4, 11%) mg/m2. For cilengitide, these were nausea, chest pain, dyspnea, and fatigue. Conclusions: PFS in the docetaxel group was greater than that of cilengitide at all doses. However, cilengitide monotherapy at a dose of 600 mg/m2 showed similar OS to docetaxel and better tolerability. Combination studies with standard chemotherapy and cilengitide are warranted. [Table: see text]

Download Full-text

Bortezomib + gemcitabine (Gem)/carboplatin (Carbo) results in encouraging survival in advanced non-small cell lung cancer (NSCLC): Results of a phase II Southwest Oncology Group (SWOG) trial (S0339)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.7017 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 7017-7017 ◽

Cited By ~ 8

Author(s):

A. M. Davies ◽

J. McCoy ◽

P. N. Lara ◽

P. H. Gumerlock ◽

J. Crowley ◽

...

Keyword(s):

Median Survival ◽

Phase Ii ◽

Advanced Nsclc ◽

Response Rate ◽

Phase Ii Study ◽

Performance Status ◽

Single Agent ◽

Stage Iiib ◽

Phase Iii ◽

Survival Times

7017 Background: Bortezomib (PS-341), a small molecule proteasome inhibitor, has single agent activity in NSCLC and potentiates Gem/Carbo in pre-clinical models in a sequence-specific manner (Mortensen, Cancer Chem Pharm, 2004). A phase I trial of Gem/Carbo + PS-341 in patients (pts) with advanced NSCLC yielded an encouraging response rate of 48%. Here we describe the results of a SWOG phase II study of this regimen in advanced NSCLC. Methods: 114 eligible chemonaive stage IV and selected stage IIIB (pleural effusion) NSCLC pts received Gem 1000 mg/m2 on days 1, 8 and Carbo AUC 5 on day 1, followed 1 hour later by PS-341 1.0 mg/m2 on days 1, 4, 8, 11, with cycles repeated every 3 weeks. Non-progressing pts could continue PS-341 alone after 4 cycles. Results: Pt characteristics: Median age: 64 years; Sex M/F = 68/46; Performance status 0/1 = 50/64; stage IIIB/IV = 13/101. Response rate: 20% (95% CI 13–29%); 66% (95% CI 56–75%) had stable disease. At a median follow-up of 13 months, progression free and median survival times were 5 months (95% CI 3.5–5.3) and 11 months (95% CI 8.2–12.5). One-year survival was 46% (95% C.I. 37–55%). Most common grade 3/4 toxicities: neutropenia (52%), thrombocytopenia (63%), and fatigue (13%). Ongoing correlative studies are examining markers of proteasome inhibition (Bcl2 family, NFKB, IKB) and hypoxia (PAI-1, VEGF, OPN, HIF-1) in tumor tissue and surrogate specimens. Conclusions: The 11 month median survival achieved with the addition of PS-341 to Gem/Carbo in this phase II study is unprecedented in prior SWOG trials in advanced NSCLC, and does not appear to be explained by altered patient characteristics. The toxicity profile of this regimen is favorable. A phase III trial of Gem/Carbo ± Bortezomib in advanced stage NSCLC is under development. Supported by CA38926, CA32102. No significant financial relationships to disclose.

Download Full-text

A phase II study of high-dose cisplatin and VP-16 in neuroblastoma: a report from the Société Française d'Oncologie Pédiatrique.

Journal of Clinical Oncology ◽

10.1200/jco.1987.5.6.941 ◽

1987 ◽

Vol 5 (6) ◽

pp. 941-950 ◽

Cited By ~ 43

Author(s):

T Philip ◽

R Ghalie ◽

R Pinkerton ◽

J M Zucker ◽

J L Bernard ◽

...

Keyword(s):

Hearing Loss ◽

Phase Ii ◽

Phase Ii Study ◽

Bone Marrow Involvement ◽

Stage Iv ◽

Observation Time ◽

Phase Iii ◽

High Dose ◽

Initial Stage ◽

Duration Of Response

Forty-seven children or adolescents with initial stage IV (42 patients) or stage III (five) advanced neuroblastoma (12 were progressing after relapse and 35 had never reached complete remission [CR] after conventional therapy) were included in a phase II study of the combination of high-dose VP-16 (100 mg/m2/d X 5) and high-dose cisplatin (CDDP) (40 mg/m2/d X 5). Twenty patients had received prior CDDP therapy (total dose, 100 to 640 mg/m2; median, 320 mg/m2) and 38 of 47 had bone marrow involvement when included in the study. The overall response rate was 55%, with 22% CR. Duration of response was 5 to 18 months, with a median of 10 months. Eight patients are still disease free, with a median observation time of 13 months, but all had received additional therapy after two courses of this regimen. Gastrointestinal toxicity was frequent but tolerable. Myelosuppression was severe but of brief duration, ie, nadir of neutrophils was observed at day 15 with 95% of the patients recovering a normal count before day 28, and nadir of platelet count was at day 17 with only two severe and reversible episodes of bleeding. The overall incidence of sepsis was 8% (seven of 92 courses), with no death related to infection. No acute renal failure was observed after two courses, and only three of 47 children experienced a clear reduction of renal function. After two courses, only two children showed a hearing loss in the 1,000 to 2,000 Hz range, although hearing loss above the 2,000 Hz level was frequently encountered. It is concluded that high-dose VP-16 and CDDP is an effective regimen in advanced neuroblastoma with acceptable toxicity. Phase III studies are needed in previously untreated patients. J Clin Oncol 5:941-950.

Download Full-text

Renal Transplantation—A Tale of Two Cities

Scottish Medical Journal ◽

10.1177/003693308002500404 ◽

1980 ◽

Vol 25 (4) ◽

pp. 269-274

Author(s):

R. F. M. Wood ◽

P. R. F. Bell ◽

J. Walls ◽

J. R. Nash ◽

D. S. MacPherson ◽

...

Keyword(s):

Renal Transplantation ◽

Survival Rate ◽

Graft Survival ◽

Initial Experience ◽

Tissue Typing ◽

Two Cities ◽

Transplant Team ◽

The Difference ◽

One Year ◽

The One

In 1974 three members of the transplant team from the Western Infirmary in Glasgow moved to the new medical school in Leicester. The initial experience with 33 patients transplanted in Glasgow was published in 1972 and this paper compares the results of that series with the first 21 patients grafted in Leicester. Despite improvements in tissue typing, better quality donor kidneys and fewer complications, there has been a failure to improve on the levels of graft survival. The overall one year graft survival rate in the Glasgow series was 79 per cent compared to 52 per cent in Leicester. In these two series the difference in results appears to be explained by blood transfusion. All the Glasgow patients had been poly-transfused but of the Leicester patients the 10 transfused pre-transplant had a one year graft survival of 90 per cent while in the 11 non-transfused patients the one year graft survival was only 18 per cent.

Download Full-text

Phase II study and long-term follow-up of patients treated with taxol for advanced ovarian adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.1992.10.11.1748 ◽

1992 ◽

Vol 10 (11) ◽

pp. 1748-1753 ◽

Cited By ~ 165

Author(s):

A I Einzig ◽

P H Wiernik ◽

J Sasloff ◽

C D Runowicz ◽

G L Goldberg

Keyword(s):

Ovarian Cancer ◽

Median Survival ◽

Phase Ii ◽

Phase Ii Study ◽

Treated Patient ◽

Objective Response ◽

Significant Activity ◽

Ovarian Adenocarcinoma ◽

Significant Toxicity ◽

Long Term Follow Up

PURPOSE Based on the results of our phase I study that demonstrated the antitumor activity of taxol in a previously treated patient with ovarian cancer, a phase II study was conducted to evaluate the efficacy of taxol in patients with metastatic ovarian cancer and to evaluate further the toxicity of taxol in this group of patients. PATIENTS AND METHODS Thirty-four patients with metastatic ovarian cancer received taxol (180 to 250 mg/m2) as a 24-hour continuous infusion. A premedication regimen was used to reduce the likelihood of an acute hypersensitivity reaction. RESULTS Six of 30 assessable patients demonstrated complete responses (one patient) or partial responses (five patients; 20%; 95% confidence interval [CI], 6% to 34%; range, 2 to 30 months). Additionally, one patient had a less than partial objective response (2 months), and two patients had stable disease for 6 and 15 months. Those responders had a median survival of 27 months, and the nonresponders had a median survival of 6 months (P = .0001). Myelosuppression was the most significant toxicity. Other adverse effects included alopecia and peripheral neuropathy. CONCLUSION Taxol has significant activity in ovarian cancer and should be studied in combination with other active agents earlier in this disease.

Download Full-text

Phase II Evaluation of Preoperative Chemoradiation and Postoperative Adjuvant Chemotherapy for Squamous Cell and Adenocarcinoma of the Esophagus

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.4.868 ◽

2000 ◽

Vol 18 (4) ◽

pp. 868-868 ◽

Cited By ~ 106

Author(s):

Elisabeth I. Heath ◽

Barbara A. Burtness ◽

Richard F. Heitmiller ◽

Ronald Salem ◽

Lawrence Kleinberg ◽

...

Keyword(s):

Survival Rate ◽

Adjuvant Chemotherapy ◽

Median Survival ◽

Phase Ii ◽

Treatment Plan ◽

Pathologic Complete Response ◽

Tumor Resection ◽

Distant Metastases ◽

Preoperative Chemoradiation ◽

Preoperative Treatment

PURPOSE: This phase II trial evaluated continuous-infusion cisplatin and fluorouracil (5-FU) with radiotherapy followed by esophagectomy. The objectives of this trial were to determine the complete pathologic response rate, survival rate, toxicity, pattern of failure, and feasibility of administering adjuvant chemotherapy in patients with resectable cancer of the esophagus treated with preoperative chemoradiation. PATIENTS AND METHODS: Patients were staged using computed tomography, endoscopic ultrasound, and laparoscopy. The preoperative treatment plan consisted of continuous intravenous infusion of cisplatin and 5-FU and a total dose of 44 Gy of radiation. Esophagogastrectomy was planned for approximately 4 weeks after the completion of chemoradiotherapy. Paclitaxel and cisplatin were administered as postoperative adjuvant therapy. RESULTS: Forty-two patients were enrolled onto the trial. Of the 39 patients who proceeded to surgery, 29 responded to preoperative treatment: 11 achieved pathologic complete response (CR) and 18 achieved a lower posttreatment stage. Five patients had no change in stage, whereas eight had progressive disease (four with distant metastases and four with increases in the T and N stages). At a median follow-up of 30.2 months, the median survival time has not been reached and the 2-year survival rate is 62%. The median survival of pathologic complete responders has not been reached, whereas the 2-year survival rate of this group is 91% compared with 51% in patients with complete tumor resection with residual tumor (P = .03). CONCLUSION: An excellent survival rate, comparable to that of our prior preoperative trial, was achieved with lower doses of preoperative cisplatin and 5-FU concurrent with radiotherapy.

Download Full-text