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Accelerated fraction radiotherapy with capecitabine as neoadjuvant therapy for borderline resectable pancreatic cancer.

ABSTRACT: BACKGROUND:A standard neoadjuvant regimen has not been defined for borderline resectable (BR) pancreatic cancer. This phase II trial was designed to determine the safety of accelerated fraction radiotherapy (AFRT) with capecitabine in patients with BR pancreatic cancer. METHODS:The patients had newly diagnosed BR adenocarcinoma of the pancreas and normal organ function. Intensity-modulated (n = 11) or 3D conformal (n = 2) radiotherapy was given to a dose of 50 Gy in 2.5-Gy fractions with capecitabine 825 mg/m(2) twice on radiation days. The primary outcome was the frequency of severe treatment-related adverse events (AEs). The study was stopped before planned interim analysis because of 2 severe (grades 4 and 5) gastric ulcerations. RESULTS:Thirteen patients were enrolled with a median age of 66 years. All patients completed treatment. Seven (54%) experienced grade 3+ treatment-related AEs. Severe gastric ulceration occurred in 2 patients despite receipt of ?43 Gy to only 1% (2-3 cm(3)) of the stomach. Lymphopenia (n = 7) was the only other severe AE that occurred in >1 patient. In 7 of the 13 patients, disease had progressed outside the pancreas at restaging. Five of the 13 underwent resection, and all had >10% viable tumor. Median progression-free survival (PFS) was 2.4 months (95% CI 1.9-5.9), and median survival was 9.1 months (95% CI 5.9-not reached). Among those who underwent resection, median PFS was 13.0 months (95% CI 4.4-not reached). Median survival was not reached. CONCLUSIONS:Given the limited efficacy signal and severe gastric ulcerations, we do not recommend this regimen for pancreatic cancer. We also do not recommend the use of high doses per fraction outside a clinical trial.

SUBMITTER: Chakraborty S

PROVIDER: S-EPMC3924761 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Accelerated fraction radiotherapy with capecitabine as neoadjuvant therapy for borderline resectable pancreatic cancer.

Chakraborty Samhita S Morris Monica M MM Bauer Todd W TW Adams Reid B RB Stelow Edward B EB Petroni Gina G Sanoff Hanna K HK

Gastrointestinal cancer research : GCR 20140101 1

<h4>Background</h4>A standard neoadjuvant regimen has not been defined for borderline resectable (BR) pancreatic cancer. This phase II trial was designed to determine the safety of accelerated fraction radiotherapy (AFRT) with capecitabine in patients with BR pancreatic cancer.<h4>Methods</h4>The patients had newly diagnosed BR adenocarcinoma of the pancreas and normal organ function. Intensity-modulated (n = 11) or 3D conformal (n = 2) radiotherapy was given to a dose of 50 Gy in 2.5-Gy fractio ...[more]

PMID: 24558510

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Project description:BackgroundThere is no agreed upon standard of care for borderline-resectable pancreatic cancer (BRPC) or locally-advanced pancreatic cancer (LAPC) patients regarding the benefit of chemotherapy or radiation alone or in combination.Patients and methodsWe completed a retrospective cohort analysis of BRPC and LAPC patients at a cancer center with expertise in multi-disciplinary pancreatic ductal adenocarcinoma (PDAC) treatment over a 5-year period from 03/01/2014 to 03/01/2019 (cut-off date). The total evaluable newly diagnosed, treatment naïve, BRPC, and LAPC patients with adequate organ function and ability to obtain treatment after multidisciplinary review was 52 patients. After analysis, patients were evaluated for rates of resection, extent of resection (R0 or R1), median progression-free survival (mPFS), and median overall survival (mOS).ResultsPatients were treated with chemotherapy alone (gemcitabine and nab-paclitaxel = 77% (20/26); FOLFIRINOX = 19% (5/26); single agent gemcitabine 3.8% (1/26)), or chemotherapy followed by chemoradiation (gemcitabine +5 Gy × 5 weeks), or chemoradiation alone prior to re-staging and potential resection. Of the 29% (15/52) of patients who went on to surgical resection, 73% (11/15) achieved R0 resection. An R0 resection was achieved in 35% (9/26) of patients treated with chemotherapy alone, 7.6% (1/13) in a patient treated with chemotherapy followed by radiation, and 7.6% (1/13) with concurrent chemoradiotherapy alone. Chemotherapy alone achieved a mPFS of 16.4 months (p < 0.0025) and mOS of 26.2 months (p < 0.0001), chemotherapy followed by chemoradiation was 13.0 months and 14.9 months respectively, while concurrent chemoradiotherapy was 6.9 months and 7.3 months.Conclusions and relevanceBRPC and LAPC patients capable of surgery after only receiving neoadjuvant treatment with chemotherapy had higher rates of R0 resection with prolonged median PFS and OS compared with any patient needing combination chemotherapy with radiotherapy.

Project description:Approximately 20% of pancreatic ductal adenocarcinoma (PDAC) patients have (borderline) resectable pancreatic cancer [(B)RPC] at diagnosis. Upfront resection with adjuvant chemotherapy has long been the standard of care for these patients. However, although surgical quality has improved, still about 50% of patients never receive adjuvant treatment. Therefore, recent developments have focused on a neoadjuvant approach. Directly comparing results from neoadjuvant and adjuvant regimens is challenging due to differences in patient populations that influence outcomes. Neoadjuvant trials include all patients who have (B)RPC on imaging, while adjuvant-only trials include patients who underwent a complete resection and recovered to a good performance status without any evidence of residual disease. Guidelines recommend neoadjuvant treatment for BRPC patients mainly to improve negative resection margin (R0) rates. For resectable PDAC, upfront resection is still considered the standard of care. However, theoretical advantages of neoadjuvant treatment, including the increased R0 resection rate, early delivery of systemic therapy to all patients, directly addressing occult metastatic disease, and improved patient selection for resection, may also apply to these patients. A systematic review by intention-to-treat showed a superior median overall survival (OS) for any neoadjuvant approach (19 months) compared to upfront surgery (15 months) in (B)RPC patients. A neoadjuvant approach was recently supported by three randomized controlled trials (RCTs). For resectable PDAC, neoadjuvant treatment was superior in a Japanese RCT of neoadjuvant gemcitabine with S-1 vs. upfront surgery, with adjuvant S-1 in both arms (median OS: 37 vs. 27 months, p = 0.015). A Korean trial of neoadjuvant gemcitabine-based chemoradiotherapy vs. upfront resection in BRPC patients was terminated early due to superiority of the neoadjuvant group (median OS: 21 vs. 12 months, p = 0.028; R0 resection: 52 vs. 26%, p = 0.004). The PREOPANC-1 trial for (B)RPC patients also showed favorable outcome for neoadjuvant gemcitabine-based chemoradiotherapy vs. upfront surgery (median OS: 17 vs. 14 months, p = 0.07; R0 resection: 63 vs. 31%, p < 0.001). FOLFIRINOX is likely a better neoadjuvant regimen, because of superiority compared to gemcitabine in both the metastatic and adjuvant setting. Currently, five RCTs evaluating neoadjuvant modified or fulldose FOLFIRINOX are accruing patients.

Project description:Pancreatic ductal adenocarcinoma (PDAC) is currently ranked fourth place of cancer related mortality. Only a minority of 10-20% of patients with PDAC have a primarily resectable disease, while 50-60% of the patients are diagnosed with irresectable disease. A certain group of patients is defined as "borderline resectable", which is mainly relied to contact of the tumor to major abdominal vessels. For preoperative evaluation of resectability CT and MRI is commonly used. Although CT-scanning, which is the standard preoperative imaging modality, has striking limitations concerning evaluation of lymph node status as well as vessel involvement and approximately 20% of the patients are staged incorrectly. A central part of modern therapy of locally advanced or not primarily resectable PDAC is neoadjuvant therapy. Especially neoadjuvant chemotherapy according to the FOLFIRINOX protocol resulted in high resection rates of initially not resectable patients. Furthermore, treatment with FOLFIRINOX was shown to be an independent predictor of improved prognosis and resection after neoadjuvant treatment with FOLFIRINOX was associated with improved survival. Neoadjuvant treatment was able to increases the rates of R0 resection, which depicts an independent prognostic factor and FOLFIRINOX outmatched other treatment regimes (e.g., gemcitabine-based radio-chemotherapy) concerning achievement of a R0 resection. While most evidence of neoadjuvant treatment of PDAC is conferred by retrospective analysis, there is growing data from randomized controlled trials, confirming the beneficial effects of neoadjuvant therapy on the prognosis of PDAC. Thus, patients with borderline resectable and locally advanced PDAC should be evaluated for neoadjuvant treatment. If there is no progression of the disease during neoadjuvant treatment exploration with the goal of R0 resection should be performed. If possible, patients should be included in well-designed randomized controlled trials at specialized pancreatic centers.

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Accelerated fraction radiotherapy with capecitabine as neoadjuvant therapy for borderline resectable pancreatic cancer.

Publications

Accelerated fraction radiotherapy with capecitabine as neoadjuvant therapy for borderline resectable pancreatic cancer.

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