scholarly journals Chemoradiotherapy (Gemox Plus Helical Tomotherapy) for Unresectable Locally Advanced Pancreatic Cancer: A Phase II Study

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 663 ◽  
Author(s):  
Alessandro Passardi ◽  
Emanuela Scarpi ◽  
Elisa Neri ◽  
Elisabetta Parisi ◽  
Giulia Ghigi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Locally Advanced Pancreatic Cancer ◽  
R0 Resection ◽  
Resection Rate ◽  
Free Survival ◽  
Moderate Nausea

The aim of the study was to evaluate the safety and efficacy of a new chemo-radiotherapy regimen for patients with locally advanced pancreatic cancer (LAPC). Patients were treated as follows: gemcitabine 1000 mg/m2 on day 1, and oxaliplatin 100 mg/m2 on day 2, every two weeks (GEMOX regimen) for 4 cycles, 15 days off, hypofractionated radiotherapy (35 Gy in 7 fractions in 9 consecutive days), 15 days off, 4 additional cycles of GEMOX, restaging. From April 2011 to August 2016, a total of 42 patients with non resectable LAPC were enrolled. Median age was 67 years (range 41–75). Radiotherapy was well tolerated and the most frequently encountered adverse events were mild to moderate nausea and vomiting, abdominal pain and fatigue. In total, 9 patients underwent surgical laparotomy (5 radical pancreatic resection 1 thermoablation and 3 explorative laparotomy), 1 patient became operable but refused surgery. The overall resectability rate was 25%, while the R0 resection rate was 12.5%. At a median follow-up of 50 months, the median progression-free survival and overall survival were 9.3 (95% CI 6.2–14.9) and 15.8 (95% CI 8.2–23.4) months, respectively. The results demonstrate the feasibility of a new chemo-radiotherapy regimen as a potential treatment for unresectable LAPC.

scholarly journals The Survival Benefit of Chemoradiotherapy following Induction Chemotherapy with Gemcitabine Plus Nab-Paclitaxel for Unresectable Locally Advanced Pancreatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4733
Author(s):  
Ryoji Takada ◽  
Kenji Ikezawa ◽  
Kazuma Daiku ◽  
Shingo Maeda ◽  
Yutaro Abe ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Induction Chemotherapy ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Locally Advanced Pancreatic Cancer ◽  
R0 Resection ◽  
Free Survival ◽  
Promising Treatment ◽  
Optimal Therapeutic Strategy

An optimal therapeutic strategy for unresectable locally advanced pancreatic cancer (UR-LAPC) has not been established. This study investigated the therapeutic efficacy of chemoradiotherapy (CRT) following induction chemotherapy with gemcitabine plus nab-paclitaxel (GnP) (CRT group) compared with systemic chemotherapy alone (CTx group) in patients with UR-LAPC. This was a retrospective study of 63 consecutive patients with UR-LAPC treated at our department in a Japanese cancer referral center between February 2015 and July 2018. We excluded patients who underwent other regimens and those enrolled in another prospective study. The CRT group (n = 25) exhibited significantly better progression-free survival (PFS) and overall survival (OS) than the CTx group (n = 20, PFS 17.9 vs. 7.6 months, p = 0.044; OS 29.2 vs. 17.4 months, p < 0.001). In the multivariate analyses, CRT following induction chemotherapy was identified as an independent prognostic factor for OS. Seven (15.6%) patients underwent conversion surgery, all of whom were in the CRT group. The R0 resection rate was 85.7% (6/7). In summary, patients with UR-LAPC experienced favorable treatment outcomes after receiving GnP as the first-line chemotherapy, especially when receiving additional CRT. Thus, this treatment strategy represents a promising treatment option for selected patients with UR-LAPC.

scholarly journals Effectiveness of Carbon Ion Radiation in Locally Advanced Pancreatic Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jakob Liermann ◽  
Patrick Naumann ◽  
Fabian Weykamp ◽  
Philipp Hoegen ◽  
Juergen Debus ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Local Control ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Locally Advanced Pancreatic Cancer ◽  
Carbon Ion Radiotherapy ◽  
Free Survival ◽  
Carbon Ion

PurposeEffective treatment strategies for unresectable locally advanced pancreatic cancer (LAPC) patients are eagerly warranted. Recently, convincing oncological outcomes were demonstrated by carbon ion radiotherapy. Nevertheless, there is a lack of evidence for this modern radiation technique due to the limited number of carbon ion facilities worldwide. Here, we analyze feasibility and efficacy of carbon ion radiotherapy in the management of LAPC at Heidelberg Ion Beam Therapy Center (HIT).MethodsBetween 2015 and 2020, 21 LAPC patients were irradiated with carbon ions with a total dose of 48 Gy (RBE) in single doses of 4 Gy (RBE). Three patients (14%) were treated with concomitant chemotherapy with gemcitabine 300 mg/m2 body surface weekly. Toxicity rates were extracted from the charts. Overall survival, progression free survival, local control, and locoregional control were evaluated using Kaplan–Meier estimates.ResultsOne patient developed ascites CTCAE grade III during radiotherapy, which was related to a later histologically confirmed metachronous peritoneal carcinomatosis. No further higher-graded toxicity could be observed. The most common symptoms were nausea and abdominal pain. After a median estimated follow-up time of 19.1 months, the median progression free survival was 3.7 months, and the median overall survival was 11.9 months. The estimated 1-year local control and locoregional control rates were 89 and 84%, respectively.ConclusionCarbon ion radiotherapy of LAPC patients is safely feasible. Local tumor control rates were high. Nevertheless, compared to historical data, an overall survival improvement could not be observed. This could be explained by the poor prognosis of the selected underlying patients that mostly did not respond to prior chemotherapy as well as the early and frequent emergence of distant metastases that demonstrate the necessity of additional chemotherapy in further studies.

scholarly journals Clinical outcomes of FOLFIRINOX in locally advanced pancreatic cancer: A single center experience.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 480-480
Author(s):  
Jongchan Lee ◽  
Jong-Chan Lee ◽  
Hyoung Woo Kim ◽  
Jaihwan Kim ◽  
Jin-Hyeok Hwang
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Outcomes ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Dose Intensity ◽  
Locally Advanced Pancreatic Cancer ◽  
Future Research ◽  
R0 Resection ◽  
Nccn Guidelines

480 Background: Approximately, one third of pancreatic cancer patients have locally advanced status at diagnosis. Systemic chemotherapy or chemoradiotherapy is the main option for patients with locally advanced pancreatic cancer (LAPC). Recently, many studies have been investigating the efficacy of FOLFIRINOX (5-fluorouracil [5-FU], oxaliplatin, irinotecan and leucovorin) in LAPC patients. The aim of this study is to assess the clinical outcomes of FOLFIRINOX in patients with LAPC. Methods: Patients with LAPC who received FOLFIRINOX as an initial chemotherapy were identified via the Seoul National University Bundang Hospital database warehouse retrospectively. Demographic characteristics, disease status, chemotherapy duration and cumulative relative dose intensity (cRDI), conversion to resection and clinical outcomes were reviewed. Resectabilitywas determined based on National Cancer Comprehensive Network (NCCN) guidelines version 1.2016. Results: Fifty-one LAPC patients between Apr. 2012 and Dec. 2015 were enrolled. The median age of the patients was 60 years (30-77 years). The median overall survival (OS) of total patients was 13.3 months. The number of treatment cycles administered was 10 (2-20) and cRDI was 69.2% (35.6-91.2%). Fourteen of 51 patients (27.5%) underwent surgery and R0 resection was achieved in 11 patients (78.6%). Three patients received preoperative radiotherapy. The median OS of resected patients did not reach the 50% mark during the follow-up period compared with 13.3 months of OS in the patients without resection. Eleven of 14 resected patients did not experience recurrence during the follow-up of 10.7 months (1.8-23.5 months). The cRDI was higher in resected patients versus others (71.5 vs. 66.7%). The median time to resection was 6.7 months (3.2-14.3 months). Conclusions: FOLFIRINOX is considerable active regimen in patients with LAPC promising R0 resection rate. Future research should assess adequate duration and dose intensity of FOLFIRINOX and proper point of radiotherapy in the patients with LAPC to achieve higher rate of R0 resection.

scholarly journals Dose Escalation Trial of the Wee1 Inhibitor Adavosertib (AZD1775) in Combination With Gemcitabine and Radiation for Patients With Locally Advanced Pancreatic Cancer

2019 ◽  
Vol 37 (29) ◽  
pp. 2643-2650 ◽  
Author(s):  
Kyle C. Cuneo ◽  
Meredith A. Morgan ◽  
Vaibhav Sahai ◽  
Matthew J. Schipper ◽  
Leslie A. Parsels ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Radiation Therapy ◽  
Phase Ii ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Locally Advanced Pancreatic Cancer ◽  
Free Survival ◽  
Recommended Phase Ii Dose

PURPOSE AZD1775 (adavosertib) is an inhibitor of the Wee1 kinase. In this study, we built on our preclinical studies to evaluate the safety and efficacy of AZD1775 in combination with gemcitabine and radiation in patients with newly diagnosed locally advanced pancreatic cancer. PATIENTS AND METHODS Thirty-four patients with locally advanced pancreatic cancer were enrolled with the intention to receive four 21-day cycles of gemcitabine (1,000 mg/m2 days 1 and 8) with AZD1775 (once daily on days 1, 2, 8, and 9). Cycles 2 and 3 were administered concurrently with radiation, and cycles 5 to 8 were optional. AZD1775 was dose escalated using a time-to-event continual reassessment method on the basis of the rate of dose-limiting toxicities within the first 15 weeks of therapy. The primary objective was to determine the maximum tolerated dose of AZD1775 given in conjunction with gemcitabine and radiation. Secondary objectives were to estimate overall and progression-free survival and determine pharmacodynamic activity of AZD1775 in surrogate tissues. RESULTS The recommended phase II dose of AZD1775 was 150 mg/d. Eight patients (24%) experienced a dose-limiting toxicity, most commonly anorexia, nausea, or fatigue. The median overall survival for all patients was 21.7 months (90% CI, 16.7 to 24.8 months), and the median progression-free survival was 9.4 months (90% CI, 8.0 to 9.9 months). Hair follicle biopsy samples demonstrated evidence of Wee1 inhibition with decreased phosphorylation of cyclin-dependent kinase 1 staining by immunohistochemistry after AZD1775 administration at the recommended phase II dose. CONCLUSION AZD1775 in combination with gemcitabine and radiation therapy was well tolerated at a dose that produced target engagement in a surrogate tissue. The overall survival is substantially higher than prior results combining gemcitabine with radiation therapy and warrants additional investigation.

scholarly journals A novel event-free survival endpoint in locally advanced pancreatic cancer

2021 ◽  
Vol 13 ◽  
pp. 175883592110595
Author(s):  
Pascal Hammel ◽  
Ewa Carrier ◽  
Mairead Carney ◽  
Mark Eisner ◽  
Thomas Fleming
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Disease Free Survival ◽  
Locally Advanced Pancreatic Cancer ◽  
R0 Resection ◽  
Therapeutic Effects ◽  
Event Free Survival ◽  
Borderline Resectable ◽  
Free Survival

The treatment paradigm for locally advanced pancreatic cancer (LAPC) is evolving rapidly. The development of neoadjuvant therapies composed of combination therapies and the evaluation of their impact on conversion to borderline resectable (BR) status, resection, and ultimately overall survival (OS) are presently being pursued. These efforts justify re-visiting study endpoints in order to better predict therapeutic effects on OS, by capturing not only the achievement of R0 resection at the end of induction therapy but also the long-term reductions in the rate of local and distal recurrence. The proposed herein event-free survival (EFS) endpoint, with its novel definition specific to LAPC, is formulated to achieve these objectives. It is an analog to disease-free survival (DFS) endpoint in the adjuvant setting applied to the neoadjuvant setting and may be a valuable surrogate endpoint for this patient population.

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