A safety and efficacy trial of lethally irradiated allogeneic pancreatic tumor cells transfected with the GM-CSF gene in combination with adjuvant chemoradiotherapy for the treatment of adenocarcinoma of the pancreas

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3010-3010 ◽  
Author(s):  
D. Laheru ◽  
C. Yeo ◽  
B. Biedrzycki ◽  
S. Solt ◽  
E. Lutz ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Surgical Resection ◽  
Cell Lines ◽  
Pancreatic Tumor ◽  
Pancreas Cancer ◽  
Adjuvant Chemoradiotherapy ◽  
Published Data ◽  
Gm Csf ◽  
Disease Free

3010 Background: Pancreatic cancer remains the fourth leading cause of cancer related deaths in the US in 2006. Surgical resection provides the only possibility of cure. A standard adjuvant treatment approach for patients with resected disease has not yet been determined. We have developed an irradiated GM-CSF transfected allogeneic whole cell line pancreas adenocarcinoma vaccine. We have previously reported a follow-up 60 patient study in this same population using the highest bioactive vaccine dose identified in the initial phase I study. Methods: Single institution phase II study of 60 patients with resected pancreatic adenocarcinoma administered a total of 5 vaccines using two pancreatic cancer cell lines each delivering 2.5 X 10 8 cells ID. Vaccine one was administered 8–10 weeks following surgical resection. Patients subsequently were treated with 5-FU CI based chemotherapy integrated with radiotherapy. Patients who were disease-free one month after completion of chemoradiotherapy received vaccines 2–4, each 1 month apart. A fifth and final booster vaccine was administered 6 months after vaccine 4. The objectives of the study were: 1. To estimate overall survival and disease-free survival in patients with minimal residual disease treated with adjuvant chemoradiotherapy in sequence with the irradiated allogeneic GM-CSF transfected pancreatic tumor cell lines. 2. To characterize toxicities associated with intradermal injections of the vaccine. Results/Conclusions: The study completed enrollment of new patients in January 2005. Median follow-up for these patients is approximately 36 months. 1) The administration of a GM-CSF allogeneic pancreas cancer vaccine is safe and well tolerated; 2) The median survival is approximately 26 months. These results compare favorably with published data for resected pancreas cancer; 3) A matched cohort analysis comparing patients enrolled on this adjuvant vaccine study to the Johns Hopkins Surgery database of patients receiving surgery followed by chemoradiotherapy alone will be presented at this meeting; 4) Immune correlates will be presented at this meeting. No significant financial relationships to disclose.

Novel Allogeneic Granulocyte-Macrophage Colony-Stimulating Factor–Secreting Tumor Vaccine for Pancreatic Cancer: A Phase I Trial of Safety and Immune Activation

2001 ◽  
Vol 19 (1) ◽  
pp. 145-156 ◽  
Author(s):  
Elizabeth M. Jaffee ◽  
Ralph H. Hruban ◽  
Barbara Biedrzycki ◽  
Daniel Laheru ◽  
Karen Schepers ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I Trial ◽  
Tumor Vaccine ◽  
Colony Stimulating Factor ◽  
Tumor Vaccines ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Disease Free

PURPOSE: Allogeneic granulocyte-macrophage colony-stimulating factor (GM-CSF)–secreting tumor vaccines can cure established tumors in the mouse, but their efficacy against human tumors is uncertain. We have developed a novel GM-CSF–secreting pancreatic tumor vaccine. To determine its safety and ability to induce antitumor immune responses, we conducted a phase I trial in patients with surgically resected adenocarcinoma of the pancreas. PATIENTS AND METHODS: Fourteen patients with stage 1, 2, or 3 pancreatic adenocarcinoma were enrolled. Eight weeks after pancreaticoduodenectomy, three patients received 1 × 107 vaccine cells, three patients received 5 × 107 vaccine cells, three patients received 10 × 107 vaccine cells, and five patients received 50 × 107 vaccine cells. Twelve of 14 patients then went on to receive a 6-month course of adjuvant radiation and chemotherapy. One month after completing adjuvant treatment, six patients still in remission received up to three additional monthly vaccinations with the same vaccine dose that they had received originally. RESULTS: No dose-limiting toxicities were encountered. Vaccination induced increased delayed-type hypersensitivity (DTH) responses to autologous tumor cells in three patients who had received ≥ 10 × 107 vaccine cells. These three patients also seemed to have had an increased disease-free survival time, remaining disease-free at least 25 months after diagnosis. CONCLUSION: Allogeneic GM-CSF–secreting tumor vaccines are safe in patients with pancreatic adenocarcinoma. This vaccine approach seems to induce dose-dependent systemic antitumor immunity as measured by increased postvaccination DTH responses against autologous tumors. Further clinical evaluation of this approach in patients with pancreatic cancer is warranted.

A phase II evaluation of aerosolized GM-CSF (AGM-CSF) plus standard I-MAP/ GM-CSF/MAP/ surgery/ irradiation in the reduction of pulmonary metastases (P-METS) in soft tissue sarcoma (STS) patients (PTS)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10058-10058
Author(s):  
S. H. Okuno ◽  
M. R. Mahoney ◽  
B. F. Kabat ◽  
R. M. Marks ◽  
W. J. Maples ◽  
...  
Keyword(s):  
Pulmonary Metastases ◽  
Treatment Sequence ◽  
Debulking Surgery ◽  
Gm Csf ◽  
Median Size ◽  
Proximal Extremity ◽  
Ecog Ps ◽  
Disease Free ◽  
Free Rate

10058 Background: P-METs remain illusive with standard treatments for STS. AGM-CSF demonstrated tolerability with promising efficacy in reducing P-METS. We evaluated the 2-yr P-MET free rate in chemonaiive pts with extremity STS. Methods: ECOG PS 0/1 and Gr 3/4 primary STS of the limb girdle/extremities, were required. Treatment sequence: 2 cycles of IMAP (Ifosfamide, Mitomycin, Doxorubicin, Cisplatin) plus s.q. GM-CSF (preload d -6 to -3, d1–14); MAP (d0, 28) during irradiation (d1–35) plus AGM-CSF 250 mcg bid (d1–7, 15- 22, 28–35); surgery; post-op irradiation plus AGM-CSF 250 mcg bid (d1–7, 15–22, 28–35, 42–49). 6 of 35 pts with P-METS in ≤ 2 yrs implied lack of efficacy w.r.t. reducing P-METS. Results: 38 eligible pts were enrolled (20 male, median age 51 yrs, 24 PS 0). Median size of tumor 9 cm (2.3–26.7 cm).Location of tumors included: proximal extremity-16, distal extremity-11, and limb girdle-12. 79% received debulking surgery; 29 rendered disease-free. 38 pts are evaluable for toxicity (see table ). More common Gr 3+ events related to treatment appear below. 79% had Gr 4 neutropenia, despite s.q. GM-CSF. 6 pts have died, with 2.5 yrs median follow-up on survivors (range .4- 4.6). No treatment related fatalities occurred. 10 pts had P-METS ≤ 2 yrs. The estimated 2 yr P-MET free rate is 75% (95% CI 62–91). Conclusions: Although high, neutropenia was as expected. AGM-CSF failed to improve the 2 yr P-MET free rate in this group of STS pts. Other strategies need to be explored. Supported by NIH Grant CA15083–32 and Berlex Corporation. Max Severity (Gr 3+) [Table: see text] No significant financial relationships to disclose.

Preoperative gemcitabine based chemoradiotherapy in locally advanced nonmetastatic pancreatic adenocarcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15677-e15677
Author(s):  
D. Maximous ◽  
M. E. Abdel-Wanis ◽  
M. A. Aboziada ◽  
M. I. El-Sayed ◽  
A. A. Abd-Elsayed
Keyword(s):  
Pancreatic Cancer ◽  
Surgical Resection ◽  
Locally Advanced ◽  
Tumour Response ◽  
Metastatic Pancreatic Cancer ◽  
Surgical Reconstruction ◽  
Biliary Leakage ◽  
Dismal Prognosis ◽  
Radical Surgical Resection

e15677 Background: Almost 30% of patients with pancreatic cancer present with locally advanced tumours in absence of distant metastasis. Because surgical resection is often contraindicated by vascular invasion, this disease has a dismal prognosis. The combination of gemcitabine with concurrent radiation therapy is a promising approach that is being investigated in patients’ unresectable pancreatic cancer. Aim of the work: The efficacy of preoperative gemcitabine based chemo-radiotherapy in increasing the resectability rate for patients locally advanced, non metastatic pancreatic cancer was assessed. Methods: 25 patients were treated by preoperative gemcitabine based chemo-radiotherapy. Approximately 6 weeks after completion of chemo radiation, evaluation was performed regarding tumour response and resectability. Pancreatico-duodenectomy was done for operable patients with surgical reconstruction. Results: Patients who achieved complete remission (CR) were 2 out of 25 patients while those achieved partial remission (PR) were 11 out of 25, 6 of them were considered operable. Thus Pancreatico- duodenectomy was done for 8 patients with surgical reconstruction. The postoperative 30 day mortality occurred only in one patient. The postoperative morbidity occurred in the form of minor biliary leakage occurred only in 1 patient & leakage from gastrointestinal anaestomosis in 1 patient. Out of 8 patients who underwent radical surgical resection, only one patient developed local recurrence and simultaneous liver metastasis during the follow up period. The median survival was 12 months. Conclusions: preoperative gemcitabine based chemoradiation might benefit patients with locally advanced non metastatic pancreatic cancer by increasing the resectability without significant acute toxicity. No significant financial relationships to disclose.

Comparison of long-term outcome between endoscopic submucosal dissection and surgical resection for early gastric cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 144-144
Author(s):  
Boo Gyeong Kim ◽  
Byung-Wook Kim ◽  
Joon Sung Kim ◽  
Sung Min Park ◽  
Keun Joon Lim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rate ◽  
Surgical Resection ◽  
Disease Free Survival ◽  
Overall Survival Rate ◽  
Free Survival ◽  
Resection Group ◽  
Disease Free

144 Background: The aim of this study is to evaluate the long-term clinical and oncologic outcome of ESD for differentiated EGC of an expanded indication compared to surgical resection. Methods: Retrospective analyses were performed in patients who underwent ESD or surgical resection for EGC of an expanded indication from 2006 and 2008 in Incheon St. Mary’s Hospital, Seoul St. Mary’s Hospital, Yeouido St. Mary’s Hospital, and St. Paul’s Hospital. First arm study was performed according to pre-ESD diagnosis including pathologic diagnosis and endoscopic findings. Second arm study was obtained from post-ESD final pathologic result. All the patients were checked with endoscopy and stomach CT regularly at least 5 years. Clinical outcomes, disease free survival and overall survival were compared between the ESD group and surgical resection group in each arm. Results: In first arm study, 41 patients who received ESD and 106 patients who received surgical resection were enrolled. Metachronous recur was found in 4 patients among ESD group and in 2 patients among surgical resection group during the follow up period. There was no local recurrence in both groups. The disease free survival was not different between the two groups (ESD vs surgical resection; 87.8 vs 95.3%, p=0.291). The 5-year overall survival rate was 100% in both groups. In second arm study, 74 patients who received ESD and 165 patients who received surgical resection were enrolled. Metachronous recur was found in 5 patients among ESD group and in 2 patients among surgical resection group during the follow up period. Local recurrence did not occur in both groups. Surgical resection group was superior to ESD group in disease free survival (97.6% vs 87.6%, p=0.002). The 5-year overall survival rate was 100% in both groups. Conclusions: ESD for EGC might be acceptable considering the overall survival rates. However, intensive surveillance should be performed to find the metachronous recur after ESD.

Retrospective review of FOLFIRINOX in local advanced pancreatic cancer: Single institution experience.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15714-e15714
Author(s):  
Ashish Manne ◽  
Sushanth Reddy ◽  
Martin Heslin ◽  
Rojymon Jacob ◽  
Selwyn M. Vickers ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Surgical Resection ◽  
Retrospective Review ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Metastatic Setting ◽  
Significant Difference ◽  
One Year

e15714 Background: Although combination of fluorouracil, irinotecan, Leucovorin and oxaliplatin [FOLFIRINOX] significantly increases survival in metastatic pancreatic cancer (MPC) compared to gemcitabine based on ACCORD trial, the efficacy and toxicities may be different in non-metastatic setting. We reviewed our institution’s experience with FOLFIRINOX in locally advanced pancreatic cancer (LAPC). Methods: We performed a retrospective review of clinical outcomes in patients diagnosed with LAPC and receiving between June 2010 and July 2015, with at least one year of follow up from diagnosis, at University of Alabama at Birmingham. Results: Total of 41 patients with ECOG performance scale of 0 or 1, who underwent neoadjuvant chemotherapy with FOLFIRINOX were assessed for clinical and pathological characteristics. Median age was 61 years (range 38-81) with 23 (56.1%) males, 28 (68.3%) Caucasians and 16 (39.0%) underwent surgery (whipple operation) post-neoadjuvant. Median OS (time of diagnosis to last follow up/death) is 83.5 months for whole cohort, survival rates are 94.9% at 1 year, 58.4% at 2 year, and 33.3% at 5 year.Median OS for those who underwent surgical resection following the chemotherapy is 38.6 months; 100% at one year, 85.1% at 2 year, 55.3% at 5 year; while median OS for those who did not undergo surgery is 21.8 months; 91.7% at one year, 41.5% at 2 year, 20.7% at 5 years. Among those who underwent surgery, the median recurrence free survival (time from surgery to relapse/progression) is 19.9 months with liver being common recurrence site (81%). There was no post-operative mortality in 30 days. Grade 3-4 toxicity occurred in 46% ( vomiting (12%), fatigue (28%) and neutropenia (54%), febrile neutropenia (9%)). There is a significant difference between surgery and non-surgery groups (p = 0.012) for improved OS by log-rank test. Conclusions: Neoadjuvant FOLFIRINOX treatment associated with high response rates leading to surgical resection in our cohort. Patients who underwent neoadjuvant chemotherapy followed by resection for LAPC have statistically significant improved OS compared to those who did not.

scholarly journals Fusobacterium nucleatum infection induces pancreatic cancer cell proliferation and migration through regulation of host cytokine signaling

2021 ◽  
Author(s):  
Barath Udayasuryan ◽  
Tam T.D. Nguyen ◽  
Ariana Umana ◽  
LaDeidra Monet Roberts ◽  
Raffae A Ahmad ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Pancreatic Tumor ◽  
Pancreatic Cancer Cell ◽  
Fusobacterium Nucleatum ◽  
Cellular Migration ◽  
Gm Csf ◽  
Pancreatic Cancer Cells

Pancreatic ductal adenocarcinoma (PDAC) harbors a complex tumor microbiome that has been implicated in cancer progression and resistance to chemotherapy. Recent clinical investigations uncovered a correlation between high loads of intratumor Fusobacterium nucleatum and decreased patient survival. Here we show that pancreatic cancer cell lines harboring intracellular F. nucleatum secrete elevated levels of cancer-associated cytokines including IL-8, CXCL1, GM-CSF, and MIP-3α. We report that GM-CSF directly increases the proliferation of pancreatic cancer cells, and contributes to increased cellular migration, notably in the absence of immune cell participation. This study is the first to investigate the direct impact of F. nucleatum infection on pancreatic cancer cells. Our results suggest that F. nucleatum within the pancreatic tumor microenvironment elicits infection-specific cytokine secretion that directly contributes adversely to cancer progression and warrants further research into therapeutic manipulation of the pancreatic tumor microbiome.

Idiotype vaccine therapy of follicular lymphoma in first remission: Association of t(14;18) and disease free survival in a phase II cohort

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7582-7582
Author(s):  
B. L. Gause ◽  
S. S. Neelapu ◽  
C. M. Cohen ◽  
L. M. Katz ◽  
T. Watson ◽  
...  
Keyword(s):  
Ad Hoc ◽  
Chromosomal Translocation ◽  
Disease Free Survival ◽  
Keyhole Limpet Hemocyanin ◽  
Rank Test ◽  
Chi Square ◽  
Free Survival ◽  
Gm Csf ◽  
Disease Free

7582 Background: A single-arm Phase 2 study (Nature Med 5:1171–7,1999), evaluated the ability of tumor-specific idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) administered with granulocyte-monocyte colony-stimulating factor - GM-CSF (BiovaxID vaccine) to induce complete remission (CR) and molecular remission (MR) in follicular NHL patients in first CR after chemotherapy. We reported (ASH 2005, Abstr 2441) that at 9.2 years follow-up, disease free survival (DFS) and overall survival (OS) were 45% and 95%, respectively; median DFS was 8.0 years. Previous studies indicated that the t(14;18) chromosomal translocation is associated with follicular NHL. We tested the hypothesis that absence of t(14;18) in peripheral blood (PB) of patients after Id vaccination is predictive of DFS. Methods: A 20-patient cohort in first CR treated with the vaccine was evaluated. t(14;18)- (MR) is defined as <1 t(14;18)+ cell in 105 cells using PCR of the MBR breakpoint cluster on DNA from tumor biopsies or PB. Of the 20 patients, 11 had t(14;18)+ tumors and PB before chemotherapy. Following chemotherapy all 11 patients continued to have t(14;18)+ PB despite being in CR. However, at 1 month following final vaccine treatment, 8 of these patients had converted to t(14;18)- . In this ad hoc analysis, the proportion of patients remaining in DFS was stratified by t(14;18) status; Kaplan-Meier analysis compared median DFS of patients across t(14;18) status following vaccination. Results: At median follow-up of 9.2 years, 55% of patients had clinically relapsed. Although not statistically significant, of the 17 patients t(14;18)- post-vaccine, only 47.1% had clinically relapsed while 100% of the 3 t(14;18)+ patients had relapsed [Chi-square test; P=0.089]. Median DFS in t(14;18)+ patients was 60 months (5.0 years) and had not yet been reached in t(14;18)- patients at 91 months (7.6 years) [Log-rank test; P=0.069]. Conclusions: These data show a possible association between t(14;18) negativity following vaccine and prolonged DFS. Additional follow-up on these patients is needed, as well as similar analyses in other cohorts, to further explore this association. [Table: see text]

The role of Notch3 signaling pathway in pancreatic cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21049-21049 ◽  
Author(s):  
T. Dang ◽  
k. Vo ◽  
K. Washington ◽  
J. Berlin
Keyword(s):  
Pancreatic Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreas Cancer ◽  
Human Cancer ◽  
Pancreatic Cancer Cell Line ◽  
Pancreatic Tissue ◽  
Tissue Array ◽  
Pancreatic Cell

21049 Background: Given the extremely poor prognosis of patients diagnosed with pancreatic cancer, identifying new targets for therapeutic intervention is crucial in improving clinical outcome. Existing data support a role for Notch3 pathway in human cancer, pancreas cancer in specific and in normal pancreas development. Method: We developed a pancreatic tissue array. An antibody targeting the extracellular domain of Notch3 was used to evaluate expression levels, grading from 0 to 4+ to determine the prevalence of Notch3 in pancreatic cancer. Notch3 expression was used to correlate with clinical data (IRB approved). Using small interfering RNA (siRNA) we tested the downstream effects of Notch3 in pancreatic cancer cell line BxP3 in vitro. Furthermore, to study pharmacologic inhibition of Notch3 processing and activation we exposed Panc-1, HPAF II and BxP3 pancreas cancer cell lines to γ-secretase inhibitors (previously demonstrated to block upstream of Notch3 thereby inhibiting Notch3). Results: Strong staining (+2 or greater) for Notch3 was seen in 50 of 72 (69%) resected specimens. No correlation with survival or tumor grade was seen. Using siRNA, we demonstrated that inhibiting Notch3 downregulated the antiapoptotic protein Bcl-xL but not Bcl-2. When γ-secretase inhibitors (GSI and L-685,458) were used, the previously mentioned pancreatic cell lines demonstrated reduction in proliferation rates. Conclusion: Notch3 overexpression is common in pancreas cancer. While Notch 3 expression does not clearly correlate with survival, our in vitro data suggest that Notch3 affects apoptotic pathways and may represent a potential target for intervention in patients with pancreatic cancer. No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document