Final results of a phase Ib study of gemcitabine plus PEGPH20 in patients with stage IV previously untreated pancreatic cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 359-359 ◽  
Author(s):  
Sunil R. Hingorani ◽  
William Proctor Harris ◽  
Joseph Thaddeus Beck ◽  
Boris A. Berdov ◽  
Stephanie Ann Wagner ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase 1 ◽  
Advanced Pancreatic Cancer ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Tumor Stroma ◽  
Clinical Activity ◽  
Phase 2 ◽  
Chemotherapy Drugs ◽  
Metastatic Sites

359 Background: Poor outcome in pancreatic cancer (PDA) has been associated with tumor stroma limiting access of chemotherapy drugs. PEGPH20 (PEG), PEGylated recombinant human hyaluronidase, which depletes hyaluronan (HA) in tumors, has demonstrated anti-tumor activity in preclinical PDA models. In a KPC model of PDA, PEG + gemcitabine (Gem) significantly prolonged survival compared to Gem alone. In Phase 1 PEG monotherapy studies, the MTD was 3µg/kg. The most common adverse events (AEs) were musculoskeletal events. Methods: This was a phase 1b study to determine the recommended phase 2 dose of PEG + Gem in patients (pts) with previously untreated Stage IV pancreatic cancer. PEG was given at 1, 1.6, or 3µg/kg IV twice weekly Wks 1–4 and weekly Wks 5–7, followed by 1 wk rest. Gem was given at 1000mg/m2IV once weekly for Wks 1–7, then 1 wk rest. Thereafter, PEG + Gem were given once weekly for 3 wks in 4-wk cycles. Dexamethasone was given pre and post PEG doses. Due to evolving SOC, the study was discontinued before initiation of the phase 2 randomization. Results: Twenty-eight pts were enrolled in the study. The majority of the patients (89%) had metastatic sites in the liver. Four, 4 and 20 pts received PEG at 1, 1.6 and 3µg/kg, respectively. The most common AEs related to PEG were muscle spasm (54%), myalgia (39%), arthralgia (29%), peripheral edema (29%), fatigue (25%), and extremity pain (18%). Median progression free survival (PFS) and overall survival (OS) were assessed and were 154 and 200 days, respectively. In an exploratory analysis, tumor biopsies from 17 pts were evaluated for HA levels (HAhigh or HAlow). 6 pts were determined to have HAhigh tumors and 11 pts had HAlow tumors. The median PFS and OS for HAhigh pts were 219 days (95% CI: 159-276) and 395 days (95% CI: 210-578). For HAlowpts median PFS and OS were 108 (95% CI: 14-163) and 174 days (95% CI: 34-293). Conclusions: PEG + Gem is generally well tolerated in advanced pancreatic cancer and shows promising clinical activity, especially in pts with HAhigh tumors. ClinicalTrials.gov Identifier: NCT01453153.

RP101 improves the efficacy of gemcitabine in treating pancreatic carcinoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14075-14075
Author(s):  
M. Haenel ◽  
D. Quietzsch ◽  
V. Heinemann ◽  
S. Boeck ◽  
R. M. Schmid ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Median Survival ◽  
Phase 1 ◽  
Advanced Pancreatic Cancer ◽  
Stage Iv ◽  
Underlying Disease ◽  
Fixed Dose ◽  
Survival Status ◽  
Phase 2 Study ◽  
One Year

14075 Background: (E)-5-(2-bromovinyl)-2’-deoxyuridine (BVDU, RP101), was initially tested in a phase 1 pilot study in pancreatic cancer. Patients (n=13) received gemcitabine (1000 mg/m2), cisplatin (50 mg/m2) and RP101 (500 mg/day). The median survival was 447 days and the TTP was 280 days. Ten of the 13 pts lived longer than one year, 4 nearly two years. Based on these promising results a phase 2 study was initiated to explore varying doses of RP101 used with a fixed dose of GEM. Methods: Pts with advanced pancreatic adenocarcinoma were eligible for treatment in this single arm study. 22 pts (16 stage IV and 5 stage III) received GEM 1000 mg/m2 on days 1, 8 and 15 of a 28-day schedule. RP101 treatment, at doses of 500, 625, 750, 875 or 1000 mg/day, was on the same day and for three days after chemotherapy. The mean age was 60 years and 73% of pts were males. Results: The results are based on interim data from an ongoing study and patients at the 2 highest dose groups are still being treated. All RP101 dose groups were combined for analyses, which included all enrolled pts. The data on the 6-month survival status show that 41% are alive; 23% dead; and 36% followed less than 6 months. The median survival (95% CI) is 7.1 months (5.9, not calculated) and 14/22 pts (64%) are still alive. The 6 month survival rate (95% CI) is 0.69 (0.52, 0.85). This compares very favorably with a large recent randomized trial in which pts who received GEM alone had a median survival (95%CI) of 5.9 months (5.1–6.7). PFS and TTP continue to be assessed in this ongoing trial. There appears to be a dose dependent increase in peak GEM levels as a function of the dose of RP101. To date, adverse events are consistent with those observed with GEM or the underlying disease. Conclusion: RP101 may improve treatment of advanced pancreatic cancer when used with gemcitabine. Updated data on survival, PFS, and safety will be presented based on available data. [Table: see text]

Retrospective comparison of modified FOLFIRINOX with full-dose FOLFIRINOX for advanced pancreatic cancer: A Japanese cancer center experience.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 469-469 ◽  
Author(s):  
Akihiro Ohba ◽  
Hideki Ueno ◽  
Yasunari Sakamoto ◽  
Shunsuke Kondo ◽  
Chigusa Morizane ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Dose Reduction ◽  
Advanced Pancreatic Cancer ◽  
Group Versus ◽  
Progression Free Survival ◽  
Cancer Center ◽  
Control Group ◽  
Phase 2 ◽  
Full Dose ◽  
Grade 3

469 Background: Various modified FOLFIRINOX (mFFX) regimens have been reported and widely used in clinical practice. Although there are retrospective studies and single-arm phase 2 studies comparing modified regimens to the full-dose regimen of the historical control group, head-to-head comparisons in the same population are limited. This study aimed to compare mFFX with full-dose FOLFIRINOX (fFFX) in patients with advanced pancreatic cancer (APC). Methods: We reviewed 85 patients with APC who received mFFX (no bolus fluorouracil and irinotecan 150 mg per square) or fFFX as first-line chemotherapy between January 2014 and December 2016. mFFX has been used since January 2016 on the basis of results of a Japanese phase 2 study. The efficacy, safety, and dose reduction pattern were evaluated. Results: A total of 56 eligible patients (26 treated with mFFX and 30 with fFFX) were selected. Baseline characteristics of each group were well-balanced. The median relative dose intensities of oxaliplatin, irinotecan, bolus fluorouracil, and continuous infusion fluorouracil were 68.6%, 78.5%, 0%, and 88.5% in the mFFX group, and 80.5%, 76.5%, 25.6%, and 83.6% in the fFFX group, respectively. Second cycle dose reduction occurred in 38% of the patients in the mFFX group and in 62% of those in the fFFX group. The median overall survival (OS) was 19.0 months in the mFFX group, compared to 13.2 months in the fFFX group (HR 0.60, 95% CI 0.25–1.47, P = 0.27). In a multivariate analysis to adjust for prognostic factors for OS, the hazard ratio for death with mFFX was significant (adjusted HR 0.36, 95% CI 0.14–0.93, P = 0.04). The median progression-free survival was 8.3 months in the mFFX group and 5.9 months in the fFFX group (HR 0.83, 95% CI 0.44–1.54, P = 0.55). The response rate was 35% in the mFFX group versus 30% (P = 0.78) in the fFFX group, respectively. Grade 3 or 4 leucopenia (15% versus 40%), neutropenia (42% versus 70%), febrile neutropenia (8% versus 17%), and nausea (4% versus 13%) were decreased in the mFFX group, but the differences were not statistically significant. Conclusions: mFFX had equivalent or higher efficacy and improved safety compared to fFFX in the same population.

Sorafenib (SOR) in advanced non-small cell lung cancer (NSCLC): A phase II study of patient progress after several lines of treatment.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18070-e18070
Author(s):  
Sergio Vazquez-Estevez ◽  
Silvia Varela ◽  
Begoña Campos ◽  
Elena Álvarez ◽  
Guillermo Quintero ◽  
...  
Keyword(s):  
Adverse Events ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Skin Toxicity ◽  
Rank Test ◽  
Clinical Activity ◽  
Histologic Type ◽  
Metastatic Nsclc ◽  
Disease Stabilization ◽  
Metastatic Sites

e18070 Background: Sorafenib is a potent inhibitor of c-Raf, b-Raf VEGFR-1/2/3 and PDGFR-β. In NSCLC, proliferative signaling through the Ras/Raf/MEK/ERK pathway is often activated from K-ras mutations. Their efficacy as monotherapy to treat advanced NSCLC has been demonstrated in several trials. In them, SOR improved the rate of disease stabilization in patients who had previously been treated with chemotherapy. Our objective is to confirm the clinical and safety results in the daily clinical activity. Methods: Between October 2008 and December 2011, patients with metastatic NSCLC and measurable disease, ECOG 0-1 were treated after having received two or more prior chemotherapy regimens for metastatic disease. SOR was administered at a starting dose of 400 mg bid continuously in 28-day cycles.The primary end points were Overall Survival (OS) and Progression Free Survival (PFS). Survival medians were estimated by the Kaplan-Meier method and comparisons between subgroups were assessed by the log-rank test. Results: Fifteen Caucasian patients were enrolled, with a mean age at diagnosis of 61 (SD = 13.5) years and most of them were males (n = 10, 67%). The predominant histologic type was adenocarcinoma (n = 9, 60%). Twelve (80%) patients were in stage IV at diagnosis. The predominant metastatic sites were lung (n = 8, 53%), lymph nodes, (n = 5, 33%), pleura (n =3, 20%) and bone (n=3, 20%).Patients received a median of 3 (range: 2 to 4) treatment lines prior to the SOR regimen, with a median duration of 80.5 (range: 9 to 247) days.Median OS and median PFS were 98 and 84 days, respectively. No significant differences in survival were found according to gender, smoking, histologic type, stage, metastatic site, ECOG nor presence of biomarkers.The toxicity profile was mild. Adverse events CTC G3/4 were dyspnea (n = 4, 27%), skin toxicity (n = 1, 7%) and vomiting (n = 1, 7%). Conclusions: In this study, patients with metastatic NSCLC receiving SOR had a median PFS of 3 months. The safety profile is acceptable, reversible and manageable without unexpected adverse events to this therapy. While still waiting for the results of ongoing trials, we can say thatSOR is safe, so far, in patients who have been widely treated.

The biomarkers of gemcitabine and erlotinib treatment in advanced pancreatic cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 358-358
Author(s):  
Kuniyasu Irie ◽  
Makoto Ueno ◽  
Satoshi Kobayashi ◽  
Yoshihiro Gouda ◽  
Shinichi Ohkawa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Multivariate Analysis ◽  
Performance Status ◽  
Univariate Analysis ◽  
Advanced Pancreatic Cancer ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Rank Test ◽  
Antiulcer Drugs ◽  
The Difference

358 Background: A combination of gemcitabine+erlotinib is one of the standard chemotherapies in advanced pancreatic cancer (APC). Since APC patients often take antiulcer drugs to prevent gastritis (e.g., NSAIDs to reduce cancer pain), erlotinib concentration is generally decreased through the mechanism of CYP3A4. Furthermore, unlike lung cancer, the biomarkers for APC are not obvious except rash. Here, we examined biomarkers of gemcitabine+erlotinib treatment in APC patients including the presence of antiulcer drugs. Methods: The subjects were 59 advanced pancreatic cancer patients. They were treated with gemcitabine+erlotinib starting from Nov. 2011 to Apr. 2013. Gemcitabine was administered at 1000 mg/m2, on days 1, 8, and 15 for every 4 weeks, and erlotinib was taken 100 mg daily. The progression-free survival (PFS), UICC stage, sex, age, CRP concentration, performance status (PS), rash, and presence of antiulcer drugs were examined. The PFS curve was plotted according to the method of Kaplan and Meier. The difference in the PFS was calculated using the log-rank test, and a multivariate analysis was conducted using Cox hazard model. Results: UICC stages were as follows; i.e., stage II: 1, stage III: 8, and stage IV: 50. There were 36 males and 23 females, and their ages ranged from 41 to 82 years old (median: 65). The CRP concentrations ranged from 0.02 to 11.5 mg/dl (median: 0.57). 37 patients received antiulcer drugs, and 48 patients had rash. The univariate analysis revealed that the CRP concentration and rash were significant (p=0.009 and p=0.005, respectively). Low CRP (<0.57mg/dl) and presence of rash were related to good PFS. The multivariate analysis also revealed that the CRP concentration (HR, 0.34; 95%CI, 0.16-072; p=0.005) and rash (HR, 0.40; 95%CI, 0.16-0.96; p=0.04) were significant. The presence of antiulcer drugs on PFS was insignificant. Conclusions: The CRP concentration and rash were biomarkers of gemcitabine+erlotinib treatment in APC patients.

Pegilodecakin as monotherapy or in combination with anti-PD-1 or tyrosine kinase inhibitor in heavily pretreated patients with advanced renal cell carcinoma (RCC): Updated results from phase I/Ib IVY study.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 679-679
Author(s):  
Aung Naing ◽  
Kyriakos P. Papadopoulos ◽  
Deborah J.L. Wong ◽  
Raid Aljumaily ◽  
Annie Hung ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Phase 1 ◽  
Performance Status ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Interleukin 10 ◽  
Median Number ◽  
Clinical Activity ◽  
Ecog Performance Status ◽  
Heavily Pretreated

679 Background: Pegilodecakin (PEG), a pegylated recombinant human interleukin-10, has demonstrated clinical benefit and manageable toxicity in advanced RCC (Naing et al. 2016 JCO, Naing et al. 2019 Lancet Oncol). As part of the multi-arm (arm A to J) phase 1 IVY study, PEG alone (Part A) or in combination with pazopanib (Part G) or anti-PD-1 (pembrolizumab or nivolumab; Parts H+I) were investigated in heavily pretreated RCC patients (pts). Methods: In a phase 1/1b study which enrolled 353 pts in the US from 2013 to 2017, we analyzed treatment-related adverse events (TRAEs) graded by CTCAE v 4.02, tumor response by irRC, progression-free survival (PFS), and overall survival (OS) for all the advanced RCC pts who received PEG-containing treatment (n=66). Data cut-off was February 19, 2019. Results: Sixty six heavily pretreated RCC pts received PEG alone (n=24, 1-20 µg/kg), with pazopanib (n=4, 10µg/kg), with pembrolizumab (n=9, 10-20 µg/kg), or with nivolumab (n=29, 10-20 µg/kg). Most pts were male (70%), median age 62.5 years, initially diagnosed as stage IV (42%) with clear cell histology (64%), ECOG performance status of 1 (58%), and intermediate/poor (73%/14%) risk per IMDC category. Patients received a median number of 2 prior therapies. Most common grade 3/4 TRAEs were anemia (32%), thrombocytopenia (15%), and hypertriglyceridemia (14%). No pts died due to a TRAE. Median follow-up was 31.5 months. Conclusions: PEG alone or in combination with anti-PD-1 or pazopanib suggested some clinical activity with manageable toxicity in advanced RCC pts. These findings support further ongoing studies of PEG combinations in RCC pts. Clinical trial information: NCT02009449 .[Table: see text]

A phase IIb trial of coix seed injection for advanced pancreatic cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15023-e15023 ◽  
Author(s):  
Mary Ann Tagliaferri ◽  
Lee Steven Schwartzberg ◽  
Michael M. Chen ◽  
Luis H. Camacho ◽  
Edward H. Kaplan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Adverse Events ◽  
Primary Liver Cancer ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Serious Adverse Events ◽  
Coix Seed

e15023 Background: Kanglaite injection (KLTi) is a purified botanical extract injection tested for pancreatic cancer. KLTi is derived from Coix seed of the plant Coix lacrama-jobi. KLTi demonstrated growth inhibitory effects in vitro. In xenograft models with PANC-1 cell lines in BALB/C mice, KLTi combined with gemcitabine had synergistic tumor inhibitory activity greater than gemcitabine alone. KLTi is approved and widely used in China to treat non-small cell lung cancer and primary liver cancer. We report final cohort 1 results from a US phase 2b clinical trial. Methods: Eligible patients with histologically confirmed unresectable pancreatic cancer were randomized to a regimen of either KLTi 30g/day plus a standard course of gemcitabine or a standard course of gemcitabine only. The two groups were compared in efficacy, measure by progression-free survival (PFS), and safety. Results: Forty-one patients were randomized to cohort 1 and 38 patients received treatment: 26 received KLTi plus gemcitabine, 12 received gemcitabine only, and 3 received no treatment. The KLTi plus gemcitabine group had a median PFS of 114 days, significantly longer than the median PFS of 57.5 days in the gemcitabine only group (HR 0.338, 95% CI: 0.145, 0.788, p=0.008). The overall response rates were 15.5% (4/26) and 8.3% (1/12) for KLTi plus gemcitabine and gemcitabine only, respectively. Two serious adverse events were possibly related to KLTi; one subject had a pulmonary embolism and the other experienced transient confusion. The adverse events were similar between the groups and consistent with gemcitabine toxicities. Conclusions: Combined with gemcitabine, KLTi injection showed favorable tolerability and encouraging clinical activity for the treatment of advanced pancreatic cancer. Clinical trial information: NCT00733850.

Necuparanib combined with nab-paclitaxel + gemcitabine in patients with metastatic pancreatic cancer: Phase 2 results.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 370-370 ◽  
Author(s):  
Eileen Mary O'Reilly ◽  
Devalingam Mahalingam ◽  
James M. Roach ◽  
Paul Justin Miller ◽  
Molly E. Rosano ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Response Rates ◽  
Complete Response ◽  
Metastatic Pancreatic Cancer ◽  
Phase 2 ◽  
Target Number ◽  
Common Grade ◽  
Grade 3

370 Background: The Phase 1 portion of a Phase 1/2 trial of Necuparanib (“Necu”) combined with nab-paclitaxel (nabP) + gemcitabine (gem) in patients with metastatic pancreatic cancer (ClinicalTrials.gov Identifier NCT01621243) showed acceptable safety and tolerability and encouraging signals of activity and established a dose for the randomized, placebo (PBO)-controlled Phase 2 portion. Methods: In Phase 2, patients received daily s.c. injections of either 5 mg/kg Necu daily or PBO, combined with i.v. 125 mg/m2 nabP and 1000 mg/m2 gem (Days 1, 8, 15 of each 28-day cycle). The primary endpoint was overall survival (OS); other endpoints included progression-free survival (PFS), response rates, safety, and CA19.9 levels. An interim futility analysis was conducted in July 2016 once 57 deaths (50% of the target number of 114 events required for trial completion) had occurred. Results: The analysis was conducted on data from 120 randomized patients (62 Necu, 58 PBO). The Z-score for futility was -0.42 (prespecified boundary of -0.148 was crossed as actual score was lower). Median OS was Necu = 10.71 and PBO = 9.99 months; hazard ratio (HR) = 1.12 (favoring PBO); OS curves were intertwined. PFS was Necu = 5.52 and PBO = 6.93 months; HR = 0.97. RECIST response rates were comparable between arms: complete response, Necu = 0%, PBO = 3%; partial response, Necu = 26%, PBO = 26%; stable disease, Necu = 31%, PBO = 34%; disease control rate, Necu = 56%, PBO = 64%. The most common Grade 3+ adverse events (AEs) were neutropenia (Necu = 33%, PBO = 33%), thrombocytopenia (Necu = 27%, PBO = 5%), and anemia (Necu = 22%, PBO = 11%). There were lower rate of serious AEs with Necu (48%) vs. PBO (60%). Modest increases in APTT, AST, and ALT were noted following Necu relative to PBO. 23% of Necu and 5% of PBO patients were IgG positive with an anti-heparin/PF4 antibody titer of ≥ 0.4 at any time. There were no treatment differences for decreases in CA19.9. Conclusions: No new safety signals were observed and the toxicity profile was considered manageable; however, Necu in combination with nabP and gem did not show a sufficient level of efficacy in metastatic pancreatic cancer to warrant continued enrollment. Clinical trial information: NCT01621243.

Veliparib (Vel) in combination with chemoradiotherapy (CRT) of carboplatin/paclitaxel (C/P) plus radiation in patients (pts) with stage III non-small cell lung cancer (NSCLC) (M14-360/AFT-07).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8510-8510
Author(s):  
David E. Kozono ◽  
Tom Stinchcombe ◽  
Joseph Kamel Salama ◽  
Jeffrey Bogart ◽  
William J. Petty ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Phase 1 ◽  
Area Under The Curve ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Stage Iii ◽  
Phase 2 ◽  
Unresectable Stage ◽  
Stage Iii Nsclc

8510 Background: CRT is standard treatment (Tx) for pts with unresectable stage III NSCLC. Vel, a potent oral PARP1/2 inhibitor, interferes with repair of chemotherapy- or radiation-induced DNA damage. In a phase 2 study, Vel showed favorable efficacy vs placebo when added to C/P in stage IV NSCLC. The reported phase 1 trial assessed the safety and efficacy of Vel + C/P-based CRT in Tx of stage III NSCLC (NCT02412371). Methods: Eligible pts (≥18 yr, unresectable stage III NSCLC, no prior NSCLC therapy) received Vel + CRT of weekly C area under the curve (AUC) 2 + P 45 mg/m2 weekly + 60 Gy (2 Gy/day) RT over 6–9 weeks (wk). Vel was dose escalated from 60 mg twice daily (BID) to 240 mg BID followed by Vel 120 mg BID added to consolidation therapy (CON) once every 3 wk of C AUC 6 + P 200 mg/m2 for 2 cycles (cohort 1–5). Cohort 6 received Vel 240 mg BID + CRT followed by Vel 240 mg BID + CON. Samples for pharmacokinetic (PK) analysis were collected on wk 4 day –3. The primary endpoint was to establish the recommended phase 2 dose (RP2D) of Vel + CRT/Vel + CON. Results: As of Sep 2018, 48 pts enrolled into cohorts 1–6 at Vel 60 mg/120 mg (n = 7), 80 mg/120 mg (n = 9), 120 mg/120 mg (n = 7), 200 mg/120 mg (n = 8), 240 mg/120 mg (n = 12), and 240 mg/240 mg (n = 5) added to CRT/CON; median age 65 yr (range, 48–81). Vel PK was dose proportional; 39 (81.3%) pts completed therapy. Grade ≥3 Tx-emergent adverse events (AEs) were reported in 37 (77.1%) pts; anemia and febrile neutropenia (10.4% each) were the most common. Serious AEs were observed in 19 (39.6%) pts. Dose-limiting toxicities occurred at 200 mg/120 mg (n = 1; influenza and pneumonia), 240 mg/120 mg (n = 1; insomnia), and 240 mg/240 mg (n = 2; febrile neutropenia, neutropenia, thrombocytopenia, esophagitis, suprapubic pain, sepsis); Vel 240 mg BID + CRT/Vel 120 mg + CON was chosen as the maximum tolerated dose/RP2D. Of 41 pts evaluable for tumor assessment, 26 (63.4%) had a confirmed response. Interim median progression-free survival was 24.1 mo (range, 8.9 – not reached); updated results will be reported. Conclusions: Vel 240 + CRT/Vel 120 mg BID + CON was well tolerated with promising antitumor activity in stage III NSCLC and was determined as RP2D. Clinical trial information: NCT02412371.

scholarly journals Failure patterns and outcomes of dose escalation of stereotactic body radiotherapy for locally advanced pancreatic cancer: a multicenter cohort study

2020 ◽  
Vol 12 ◽  
pp. 175883592097715
Author(s):  
Xiaofei Zhu ◽  
Yangsen Cao ◽  
Tingshi Su ◽  
Xixu Zhu ◽  
Xiaoping Ju ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Locally Advanced Pancreatic Cancer ◽  
Multicenter Cohort Study ◽  
Failure Patterns ◽  
Kaplan Meier ◽  
Prescription Dose ◽  
Contrast Ct

Objective: This study aims to compare recurrence patterns and outcomes of biologically effective dose (BED10, α/β = 10) of 60–70 Gy with those of a BED10 >70 Gy for locally advanced pancreatic cancer (LAPC). Methods: Patients from three centers with a biopsy and a radiographically proven LAPC were retrospectively included and data were prospectively collected from June 2012 to June 2019. Radiotherapy was delivered by stereotactic body radiation therapy. Recurrences were categorized as in-field, marginal, and outside-the-field recurrence. Patients in two groups were required to receive abdominal enhanced contrast CT or MRI every 2–3 months and CA19-9 examinations every month during follow-up. Treatment-related toxicities were evaluated every month. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method. Results: After propensity score matching, there were 486 patients in each group. The median prescription dose of the two groups was 37 Gy/5–8 f (range: 36–40.8 Gy/5–8 f) and 42 Gy/5–8 f (range: 40–49.6 Gy/5–8 f), respectively. The median OS of patients with a BED10 >70 Gy and a BED10 60–70 Gy was 20.3 months (95% CI: 19.1–21.5 months) and 18.2 months (95% CI: 17.8–18.6 months) respectively ( p < 0.001). The median PFS of the two cohorts was 15.4 months (95% CI: 14.2–16.6 months) and 13.3 months (95% CI: 12.9–13.7 months) respectively ( p < 0.001). A higher incidence of in-field and marginal recurrence was found in patients with BED10 of 60–70 Gy (in-field: 97/486 versus 72/486, p = 0.034; marginal: 109/486 versus 84/486, p = 0.044). However, more patients with BED10 >70 Gy had grade 2 or 3 acute (87/486 versus 64/486, p = 0.042) and late gastrointestinal toxicities (77/486 versus 55/486, p = 0.039) than those with BED10 of 60–70 Gy. Conclusion: BED10 >70 Gy was found to have the best survival benefits along with a higher incidence of acute and late gastrointestinal toxicities. Therefore, a higher dose may be required in the case of patients’ good tolerance.

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