Preoperative radiotherapy and docetaxel in resectable pancreatic adenocarcinoma: A phase II trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4099-4099 ◽  
Author(s):  
F. Viret ◽  
M. Ychou ◽  
V. Moutardier ◽  
V. Magnin ◽  
P. Rouanet ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pancreatic Adenocarcinoma ◽  
Median Overall Survival ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Pathological Response ◽  
Phase Iii ◽  
Additional Patient ◽  
Curative Intent ◽  
Grade 3

4099 Background: We previously reported results a phase I trial of weekly docetaxel concurrently with radiation therapy in patients (pts) with locally advanced pancreatic adenocarcinoma (Pancreas, Vol 27, N°3, 2003). We prospectively explored this regimen in 34 pts with biopsy proven potentially resectable pancreatic adenocarcinoma. Methods: Treatment consisted of concomitant radiotherapy (45 Gy within 5 weeks directed at the pancreatic tumor and regional lymphatics) with 5 weekly doses of docetaxel (30 mg/m2/week) by 1-hour infusion, followed by a complete staging evaluation 3–4 weeks after chemo-radiation. Pts without disease progression underwent surgery. Results: From May, 2003 to July, 2005, this study enrolled 34 pts (59% men) with median age 62 years (range 45–72). Median tumor size was 3 cm. Pretreatment Endoscopic Ultrasound (EUS) staging was uT1 (7 pts), uT2 (25 pts), uT3 (2pts), uN0 (26 pts) and uN1 (8 pts). Median pretreatment CA 19.9 levels was 114 (range 1–9432). All pts (97%) but one completed radiation and 91% (31 pts) received the 5 weekly doses of docetaxel. Adverse events included grade 3/4 asthenia (28%), grade 3/4 nausea/vomiting (10%), grade 3/4 anemia (7%) and grade 3/4 neutropenia (7%). Median time between diagnosis and surgery was 3.7 months (range 2.8–8.7). Ten pts (29%) presented progressive disease after chemo-radiation and one additional patient (pt) voluntary stopped treatment procedure. Twenty three pts (68%) underwent surgical procedure, which was with curative intent in 17 pts (50%). One pt died within the 30-day post operative period. Pathological response was observed in 7 pts (30%), including 2 complete response. The median Disease Free Survival (DFS) was 11 months and the 2-year DFS was 21%. The median overall survival (OS) was 14 months. The 2-year DFS for the 17 pts resected with a curative intent was 50.4%. In this subgroup, median overall survival was not reached. Conclusions: Pre-operative combination of radiotherapy and docetaxel is feasible with tolerable toxicity and with promising pathological response. A randomized phase III study comparing this regimen (radiotherapy and docetaxel) and surgery versus surgery alone is starting. Supported in part by Sanofi Aventis, France. No significant financial relationships to disclose.

A retrospective study of neoadjuvant DCF (docetaxel, cisplatin, 5-fluorouracil) for locally advanced gastric or gastro-esophageal junction adenocarcinoma (GC).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 138-138
Author(s):  
Raquel Castellanos ◽  
Vinicius Ernani ◽  
Ulas Darda Bayraktar ◽  
Lorraine Portelance ◽  
Alberto J. Montero ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Locally Advanced ◽  
Poor Response ◽  
Pathologic Response ◽  
Pathological Response ◽  
Curative Intent ◽  
Survival Difference ◽  
Grade 3 ◽  
Lost To Follow Up

138 Background: Perioperative chemotherapy (chemo) with ECF (epirubicin/cisplatin/5-fluorouracil) plus surgery improved survival over surgery alone in GC in the MAGIC trial. Herein we report our experience using DCF in the perioperative setting in patients (pts) with locally advanced GC. Methods: We conducted a retrospective IRB-approved study of pts with potentially resectable locally advanced GC who were treated with DCF with neoadjuvant intent. Pts received 3 cycles of preoperative (pre-op) DCF every 3 weeks, followed by surgery, then 3 cycles of postoperative (post-op) DCF. Patients with a poor pathologic response could be changed to radiation (RT) or an alternate chemo regimen postop. Results: A total of 41 pts were identified, 24 with gastric and 17 with GEJ adenocarcinoma. All pts received at least 1 cycle of DCF and 78% received at least 3 cycles pre-op. Five pts progressed during neoadjuvant DCF, 4 were unresectable by CT after neoadjuvant DCF and 2 were lost to follow-up. The remaining 30 pts had surgery with curative intent. Post-op, 2 pts were lost to follow-up, 12 received DCF (with 6 of these also receiving RT), 11 received a different chemo regimen due to a poor response to neoadjuvant DCF (including 6 pts who also received RT). Two pts received post-op RT only. The median PFS was 16.8 months (95% CI 7.7 - 25.9) and the median OS was 26.9 months (95% CI 18.7–35.1). The PFS was longer for pts who had a radiological or pathological response to neoadjuvant DCF (log rank p = 0.005 and 0.02 respectively) and for pts who received DCF post-op (log rank p = 0.005). Among pts who did not receive DCF post-op, there was no survival difference between the pts who were switched to an alternative chemo or chemoRT regimen post-op compared to those who received no further therapy. The most common chemo-related adverse events were anemia (27% grade 3 or 4), nausea/vomiting (17% G3 or 4), and febrile neutropenia (12%). Conclusions: The DCF regimen is well tolerated in locally advanced GC. Patients who do not have a good response (either radiologic or pathologic) to pre-op DCF appear to have a poor prognosis regardless of the post-op treatment given.

Randomized trial of adjuvant chemotherapy versus adjuvant radiation therapy for locally advanced bladder cancer after radical cystectomy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4507-4507 ◽  
Author(s):  
Mohamed S. Zaghloul ◽  
John Paul Christodouleas ◽  
Tarek Zaghloul ◽  
Andrew Smith ◽  
Ahmed Abdalla ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Bladder Cancer ◽  
Adjuvant Chemotherapy ◽  
Radical Cystectomy ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Adjuvant Radiation ◽  
Advanced Bladder Cancer ◽  
Grade 3

4507 Background: Some chemotherapy-naïve patients with locally advanced bladder cancer (LABC) after radical cystectomy (RC) are sufficiently de-conditioned that they are not candidates for adjuvant chemotherapy or decline it, even though such treatment may be warranted. There is no clear alternative adjuvant therapy for these patients, who are usually observed. In this study, we compare post-op radiotherapy (PORT) vs. adjuvant chemotherapy in a randomized clinical trial. We hypothesized that PORT can achieve comparable disease-free survival (DFS). Methods: A randomized phase III trial was opened to compare PORT vs. sequential chemo+PORT after RC for LABC & accrued from 2002–2008 at the NCI in Cairo. In 2007, a third arm comparing adjuvant chemo was added. Herein, we report the results of PORT vs. adjuvant chemo. Patients ≤70 y/o with ≥1 of the following factors (≥pT3b/T4a, grade 3, or positive nodes) with negative margins after RC + pelvic node dissection were eligible. Routine follow-up & pelvic CT q6 months were performed. PORT included 3D conformal pelvic RT (45Gy/1.5Gy BID). Chemo included gemcitabine/cisplatin x 4. Post-hoc non-inferiority exploratory analysis was performed. Results: The PORT arm accrued 78; the chemo arm accrued 45. 51% had urothelial carcinoma; 49% had squamous cell carcinoma/other. The two arms were well-balanced except for gender (p = 0.06). Two-year outcomes & overall adjusted hazard ratios (HR) for PORT vs. chemo alone were 54% vs. 47% (HR 0.65(95%CI 0.35-1.19, p = 0.16) for DFS; 92% vs. 69% (HR 0.28(95%CI 0.10-0.82), p = 0.02 for LRFS; 75% vs. 79% (HR 2.39(95%CI 0.94-6.09), p = 0.07) for DMFS; 61% vs. 60% (HR 0.94(95%CI 0.52-1.69), p = 0.83) for OS. Late grade ≥3 GI toxicity was observed in 6 PORT patients (8%) & 1 chemo patient (2%). Based on our data, there is a greater than 90% probability that the true difference in 2 yr DFS is less than 10%, the pre-specified non-inferiority margin. Conclusions: This randomized study demonstrates superior local control with PORT vs. adjuvant chemo with no significant differences in DFS, DMFS or OS. Results suggest that PORT could be an option for patients with LABC after RC who are medically unfit for adjuvant chemo or who decline it. Clinical trial information: NCT01734798.

Efficacy and tolerability of gemcytabine plus docetaxel in patients with locally advanced or metastatic adenocarcinoma of the lung

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17134-17134
Author(s):  
M. Krzakowski ◽  
D. M. Kowalski ◽  
K. Zajda ◽  
T. Denisso ◽  
P. Jaskiewicz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Total Dose ◽  
Median Overall Survival ◽  
Locally Advanced ◽  
Stage Iv ◽  
Stage Iiib ◽  
Phase Iii ◽  
Second Line Therapy ◽  
Phase Iii Trial ◽  
Adenocarcinoma Of Lung

17134 Background: Chemotherapy prolongs survival of patients with advanced non-small cell lung cancer (NSCLC). Subanalysis of a phase III trial suggests better outcome of treatment with platinum and gemcytabine containing combinations in patients with adenocarcinoma. Also docetaxel is active in NSCLC. The aim of this phase II trial was to wvaluate the efficacy and tolerability of third generation doublet (GCB and DXL) in cheminaive patients with advanced adenocarcinoma of lung. Methods: Chemonaive patients with biopsy proven stage IIIB or IV adenocarcinoma of lung not suitable for curative radical treatment witk KPS 80–100 received 2 to 6 chemotherapy cycles (DXL 80 mg/m2 day 1 plus GCB 1000 mg/m2 day 1 and 8; every 21 days). Response rate and tolerability were the primary endpionts, while the overall survival and 1-year survival were secondary objectives. Results: Twenty eigth patients (15 women, 13 men) with median age 59,04 (range 40–74) were treated. Twenty three patients was analysed. Stage IV was found in 23 (95.8%) and stage IIIB in 1 (4.2%) patients. Partial response was achiwed in 9 (37,5%), stable disease in 12 (50%) and pregressive disease in 3 (12,5%) patients. Median time to progression was 8, 37 months (range: 1.5–14 months). Median overall survival was 12,87 months (range: 4–35 months). Eleven (11) patients received second-line therapy (6-RT, 11-CTH). All patients received 94 cycles of chemotherapy (range: 2, median 3,9). Total dose of docetaxel on each patients was fro 120 to 960 mg (median 556 mg). Total dose of gemcytabine on each patients was from 2100 mg to 21000 mg (median 10475 mg). Treatment toxicicy presents on the table . Conclusions: First line gemcytabine and docetaxel containing chemotherapy is effective palliative treatment for patients with advanced AC of the lung. Toxicity was within acceptable limits. [Table: see text] No significant financial relationships to disclose.

A phase I dose escalation study of eryaspase in combination with modified FOLFIRINOX in locally advanced and metastatic pancreatic ductal adenocarcinoma.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS453-TPS453
Author(s):  
Marcus Smith Noel ◽  
Philip Agop Philip ◽  
Mohamedtaki Abdulaziz Tejani ◽  
John Marshall ◽  
Aiwu Ruth He ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase I ◽  
Pancreatic Adenocarcinoma ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

TPS453 Background: FOLFIRINOX remains the standard of care for the first line treatment of patients with locally advanced and metastatic pancreatic adenocarcinoma, however the prognosis remains poor, thus novel treatment options are indicated. Eryaspase, asparaginase (ASNase) encapsulated in red blood cells (RBCs) is an investigational product under development. Following infusion, asparagine and glutamine are actively transported into RBCs where they are hydrolyzed by the encapsulated ASNase. A randomized phase IIb study in patients with advanced pancreatic cancer whose disease progressed following first-line treatment (NCT02195180) was previously conducted. Eryaspase in combination with gemcitabine monotherapy or FOLFOX combination therapy improved overall survival (OS) and progression free survival (PFS). The safety profile of eryaspase was acceptable. A second line pivotal randomized phase III trial (Trybeca-1) is currently enrolling (NCT03665441). We design this phase I study to determine the safety of mFOLFIRINOX combined with Eryaspase in the first line of treatment. Methods: Patients with locally or metastatic biopsy proven pancreatic adenocarcinoma will be treated with the combination of mFOLFIRINOX plus Eryaspase. This will be a standard 3+3 design with 4 possible doing levels. mFOLFIRINOX dosing will include 5-Fluorouracil 2400 mg/m2 over 46 hours, Oxaliplatin 85 mg/m2, Irinotecan 150 mg/m2 plus Eryaspase 75 Units/kg at dose level 0. Eryaspase will be dose escalated up to 100 Units/kg. The study will enroll at three academic centers. Key eligibility criteria include performance status 0 or 1; locally advanced or metastatic tumor disease; adequate organ function. The primary objective is to determine the maximum tolerated dose and safety of this novel combination. Key secondary objectives include objective response rate, progression-free survival, overall survival, pharmacokinetics, pharmacodynamics, and biomarker research. A data safety monitoring committee will review data every 3 months. Clinical trial information: 04292743.

Minimal Macroscopic Residual Disease (0.1–1 cm). Is It Still a Surgical Goal in Advanced Ovarian Cancer?

2016 ◽  
Vol 26 (5) ◽  
pp. 906-911 ◽  
Author(s):  
Luis M. Chiva ◽  
Teresa Castellanos ◽  
Sonsoles Alonso ◽  
Antonio Gonzalez-Martin
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Median Overall Survival ◽  
Residual Disease ◽  
Disease Free Survival ◽  
Advanced Ovarian Cancer ◽  
Stage Iv ◽  
Phase Iii ◽  
Stage Iii ◽  
Pubmed Database

ObjectiveThe objective of this review was to try to determine by searching in the literature what is the survival in patients with advanced ovarian cancer after a primary debulking with minimal macroscopic residual disease (MMRD; 0.1–10 mm). Additionally, this review aimed to explore the survival in patients with residual disease from 0.1 to 0.5 cm.MethodsA retrospective search was accomplished in the PubMed database looking for all English-language articles published between January 1, 2007 and December 31, 2014, under the following search strategy: “ovarian cancer and cytoreduction” or “ovarian cancer and phase III trial”. We selected those articles that contain information on both percentage of MMRD (0.1–1 cm) and median overall survival (OS) in this subset of patients with stage III to stage IV ovarian cancer after primary debulking surgery.ResultsThirteen publications were obtained including information of a total 11,999 patients with stage III to stage IV ovarian cancer. Five thousand thirty-seven patients (42%) had MMRD after the primary debulking (0.1–1 cm). Median overall survival in patients with MMRD was 40 months and disease-free survival (DFS) was 16 months. This group of patients obtained an advantage of 10 months in OS (40 vs 30 m) and 4 months in DFS (16 vs 12 m) compared with the group with suboptimal debulking (P < 0.001). Compared with the group of complete resection, patients with minimal macroscopic residuum showed a significant inferior median OS and DFS of 30 months and 14 months, respectively (OS, 70 vs 40 m; DFS, 30 vs 16 m) (P < 0.001). The group of residual disease of 0.1 to 0.5 cm reached a median survival of 53 months.ConclusionsPatients with ovarian cancer with MMRD after primary surgery obtain a modest but significant advantage in survival (10 months) over suboptimal patients. Patients with macroscopic residual disease (0.1–0.5 cm) obtain a better survival (53 months) than those with more than 0.5 to 1 cm. We propose that they should be classified as a different prognostic group.

scholarly journals Comparison of outcomes and side effects for neoadjuvant chemotherapy with weekly cisplatin and paclitaxel followed by chemoradiation vs. chemoradiation alone in stage IIB–IVA cervical cancer: study protocol for a randomized controlled trial

Trials ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Jing Li ◽  
Hua Liu ◽  
Ya Li ◽  
Jian Li ◽  
Lifei Shen ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Advanced Cervical Cancer ◽  
Free Survival ◽  
Locally Advanced Cervical Cancer ◽  
Disease Free

Abstract Background Currently, the standard treatment for locally advanced cervical cancer is concurrent chemoradiation (CCRT). The effect of neoadjuvant chemotherapy in advanced cervical cancer is controversial. Studies have shown that the addition of a weekly regimen of neoadjuvant chemotherapy (NACT) followed by CCRT may be superior to a thrice-weekly regimen of NACT and CCRT. Among patients who had not received prior cisplatin, a cisplatin and paclitaxel (TP) regimen resulted in longer overall survival than other regimens. This study aims to investigate the feasibility, safety, and efficacy of NACT with weekly TP followed by CCRT. Methods This is a prospective, randomized, open-labeled, multicentered phase III study. Based on a 65% of 2-year disease-free survival (DFS) rate in the CCRT group and 80% of that in NACT followed by CCRT group, and on prerequisite conditions including an 8% loss to follow-up, a two-sided 5% of type I error probability, and an 80% of power, a total of 300 cases were required for enrollment. Patients with IIB–IVA cervical cancer will be randomly allocated in a 1:1 ratio to one of two intervention arms. In the study arm, patients will receive dose-dense cisplatin (40 mg/m2) and paclitaxel (60 mg/m2) weekly for 4 cycles followed by CCRT (45 Gy in 5 weeks concurrent with cisplatin 40 mg/m2 weekly) plus image-guided adaptive brachytherapy (IGBRT). In the control arm, patients will undergo CCRT treatment. The primary endpoint of the study is 2-year disease-free survival (DFS); the secondary endpoints are 5-year overall survival (OS) and disease-free survival (DFS), the response rate 3 months after treatment completion, grade III/IV adverse effects, and quality of life, and potential biomarkers for predicting treatment response will also be studied. Discussion The data gathered from the study will be used to determine whether NACT with weekly TP followed by CCRT may become an optimized treatment for locally advanced cervical cancer. Trial registration Chinese Clinical Trial Registry ChiCTR1900025327. Registered on 24 August 2019. medresman.org.cn ChiCTR1900025326

Randomized Phase III Trial of Gemcitabine Plus Cisplatin Compared With Gemcitabine Alone in Advanced Pancreatic Cancer

2006 ◽  
Vol 24 (24) ◽  
pp. 3946-3952 ◽  
Author(s):  
Volker Heinemann ◽  
Detlef Quietzsch ◽  
Frank Gieseler ◽  
Michael Gonnermann ◽  
Herbert Schönekäs ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Median Overall Survival ◽  
Statistical Significance ◽  
Single Agent ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Free Survival

Purpose To compare the effectiveness and tolerability of gemcitabine plus cisplatin with single-agent gemcitabine as first-line chemotherapy for locally advanced or metastatic pancreatic cancer. Patients and Methods Patients with advanced adenocarcinoma of the pancreas were randomly assigned to receive either gemcitabine 1,000 mg/m2 and cisplatin 50 mg/m2 given on days 1 and 15 of a 4-week cycle (GemCis arm) or gemcitabine alone at a dose of 1,000 mg/m2 on days 1, 8, and 15 of a 4-week regimen (Gem arm). The primary end point was overall survival; secondary end points were progression-free survival, response rate, safety, and quality of life. Results One hundred ninety-five patients were enrolled and showed baseline characteristics well balanced between treatment arms. Combination treatment in the GemCis arm was associated with a prolonged median progression-free survival (5.3 months v 3.1 months; hazard ratio [HR] = 0.75; P = .053). Also, median overall survival was superior for patients treated in the GemCis arm as compared with the Gem arm (7.5 v 6.0 months), an advantage which did not, however, reach statistical significance (HR = 0.80; P = .15). Tumor response rates were comparable between treatment arms (10.2% v 8.2%). The rate of stable disease was, however, greater in the combination arm (60.2% v 40.2%; P < .001). Grade 3 to 4 hematologic toxicity did not exceed 15% in both treatment arms. Conclusion These results support the efficacy and safety of an every-2-weeks treatment with gemcitabine plus cisplatin. Median overall survival and progression-free survival were more favorable in the combination arm as compared with gemcitabine alone, although the difference did not attain statistical significance.

Use of EGF A61G polymorphism to predict overall survival in a phase III study of gemcitabine plus cetuximab versus gemcitabine in patients with locally advanced or metastatic pancreatic adenocarcinoma (SWOG 0205).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 203-203
Author(s):  
Melissa Janae Labonte ◽  
Bryan H. Goldman ◽  
Wu Zhang ◽  
C. D. Blanke ◽  
Philip Agop Philip ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pancreatic Adenocarcinoma ◽  
Objective Response ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Entire Study ◽  
Egfr Signaling Pathway ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Phase Iii Study

203 Background: The SWOG 0205 phase III study failed to demonstrate an advantage from the addition of cetuximab to gemcitabine for overall survival (OS), progression-free survival (PFS) or objective response in advanced pancreatic cancer. Molecular markers may identify subgroups of pts who benefit from this regimen. This report summarizes the results of a pilot project aimed at screening germline single nucleotide polymorphisms (SNPs) in genes involved in gemcitabine metabolism pathway (CDA and RRM1) and EGFR signaling pathway (EGF, EGFR, IGF1, FCGR2A/3A, KRAS, IL8, COX-2, CCND1) to identify pts that may benefit from this treatment. Methods: Genomic DNA was extracted from 88 available serum samples for this molecular correlates pilot study. Sixteen SNPs were evaluated using PCR-based protocols. There were no differences in baseline characteristics or outcome between pts included in the analysis and the entire study population. Associations between genotype and OS were assessed using stratified Cox regression, with adjustment for treatment arm. Genotypes were parameterized as the number of dominant alleles. No p value adjustments were made for multiple comparisons. Results: Median age was 63.3 years (range: 29.6-85.0), and median OS (95% CI) was 5.7 months (mos) (range: 4.4-6.8) in this subset. There was a statistically significant association between EGF A61G SNP (rs4444903) genotype and OS (p=0.04). Among pts carrying the AA genotype, median OS was 8.4 mos (95% CI 4.9-15.0), as compared to 5.6 mos (95% CI 3.0-9.0) among those with the AG genotype and 5.3 mos. (95% CI 2.2-7.1) for the GG genotype. Evidence was weak for interaction between treatment arm and rs4444903 genotype (p=0.13). No significant associations between other SNPs and OS were observed. Conclusions: This exploratory study suggests that the EGF A61G polymorphism may be a useful molecular marker for predicting clinical outcomes in metastatic pancreatic adenocarcinoma pts treated with gemcitabine-based chemotherapy.

SAMIT: A phase III randomized clinical trial of adjuvant paclitaxel followed by oral fluorinated pyrimidines for locally advanced gastric cancer.

2013 ◽  
Vol 31 (18_suppl) ◽  
pp. LBA4002-LBA4002 ◽  
Author(s):  
Kazuhiro Yoshida ◽  
Akira Tsuburaya ◽  
Michiya Kobayashi ◽  
Shigefumi Yoshino ◽  
Masazumi Takahashi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Significance Level ◽  
D2 Lymph Node Dissection ◽  
Locally Advanced Gastric Cancer ◽  
Number Of Patients ◽  
Grade 3 ◽  
Fluorinated Pyrimidines

LBA4002 Background: Adjuvant chemotherapy with tegafur/uracil (UFT) used to be a tentative Japanese standard treatment and has been replaced by S-1 according to the result of the ACTS-GC trial, although there has been no direct comparison. Paclitaxel (PTX) has been widely used as one of the key drugs for unresectable GC. A randomized phase III trial with a two-by-two factorial design was planned to assess the survival benefit of sequential use of PTX and oral fluorinated pyrimidines (FPs) in comparison with FPs alone, and to compare UFT and S-1. Methods: Patients with serosa-invading GC who underwent R0/1 resection with extended (D2) lymph node dissection were randomized to receive either UFT 267mg/m2 daily (arm A), S-1 80mg/m2 daily for 2 weeks every 3 weeks (B), weekly PTX 80 mg/m2 followed by UFT (C), or PTX followed by S-1 (D) for 24 weeks. The primary endpoint was disease-free survival (DFS). 708 patients per groups were necessary to detect a hazard ratio of 0.8 with 90% power for superiority of the sequential arms, C+D, vs. A+B (two-sided 5.0% significance level). The number of patients was set to 370 per arm (total 1480) with an 88% power for noninferiority (1.33 as the margin) of UFT vs. S-1. Results: Between August 2004 and October 2007, 1,495 patients from 232 centers were randomized with the full analysis set of 1,433. Demographics were well balanced among arm A (n=359), B (n=364), C (n=355), and D (n=355); mean age was 64, 86% were PS 0, 68% of tumors were 8 cm or greater and 85% were clinically node positive. Grade 3-4 neutropenia or anorexia occurred in 11% or 6%, 13% or 7%, 13% or 2%, and 23% or 5% for arm A, B, C, and D, respectively. Other % grade 3-4 toxicities were less than 5%. Median follow-up was 1,875 days and 728 events occurred. Difference in DFS between C+D and A+B were not statistically significant (HR=0.92, 95%CI 0.80-1.07, p= 0.273). HR of A+C vs. B+D was 1.23 (95%CI 1.07-1.43) and hence the null hypothesis was not rejected. Conclusions: There was a trend for better DFS for sequential use of PTX followed by FPs. Comparison between the FPs demonstrated that UFT was inferior to S-1. Sequential PTX/S-1 is safe and effective for locally advanced GC in an adjuvant setting. Clinical trial information: C000000082.

Initial results from ASSURE (E2805): Adjuvant sorafenib or sunitinib for unfavorable renal carcinoma, an ECOG-ACRIN-led, NCTN phase III trial.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 403-403 ◽  
Author(s):  
Naomi B. Haas ◽  
Judith Manola ◽  
Robert G. Uzzo ◽  
Michael B. Atkins ◽  
George Wilding ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Dose Titration ◽  
Rank Test ◽  
Discontinuation Rate ◽  
Oral Agents ◽  
Metastatic Setting ◽  
Grade 3 ◽  
Ecog Ps

403 Background: Patients (pts) with locally advanced renal cell carcinoma (RCC) are not uniformly cured by resection. The pursuit of tolerable and effective adjuvant therapies led to this investigation of two oral agents that are widely effective in the metastatic setting. Methods: 1,943 pts with completely resected RCC (pT1b high grade to pT4 any grade N any) were stratified on risk (intermediate-high or very high), clear/non-clear histology, ECOG PS, and resection approach, and randomized equally to sunitinib daily for 4 of 6 wk cycle, sorafenib daily, or placebo, then treated for up to 1 year. The primary endpoint was disease-free survival (DFS). The study was designed to detect a 25% reduction in the hazard rate, corresponding to an improvement from 5.8 to 7.7 years median DFS. After accrual of 1322 pts, the starting dose was reduced and then individually titrated to mitigate the effect of pt discontinuation from treatment intolerance. Results: At an interim analysis conducted with 62% information, although no efficacy or futility boundaries were crossed, the Data Safety Monitoring Committee recommended release of results. Using a stratified log-rank test, there were no significant differences in DFS or overall survival between either of the experimental arms and placebo. The redesign reduced the discontinuation rate on the experimental arms from about 26% in pts starting at full dose to about 14% in pts starting at reduced dose. Most common grade ≥3 adverse events were hypertension (16%/16%/4%), hand-foot reaction (15%/33%/1%), Rash (2%/15%/<1%), and fatigue (17%/7%/3%) on sunitinib, sorafenib and placebo, respectively. (See Table.) Conclusions: In pts with locally advanced, resected RCC, adjuvant treatment with sorafenib or sunitinib should not be pursued. Dose titration reduced the treatment discontinuation rate; this finding may have relevance in other settings. Clinical trial information: NCT00326898. [Table: see text]

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