Outcomes with FOLFIRINOX for borderline resectable and locally unresectable pancreatic cancer

Boone, Brian A.; Steve, Jennifer; Krasinskas, Alyssa M.; Zureikat, Amer H.; Lembersky, Barry C.; Gibson, Michael K.; Stoller, Ronald G.; Zeh, Herbert J.; Bahary, Nathan

doi:10.1002/jso.23392

Cited by 171 publications

(147 citation statements)

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“…Moreover, PFS may be biased due to the lack of standardized on-treatment imaging in retrospective studies. Secondly, the results of this meta-analysis may be biased because studies used different definitions for LAPC; three studies used the NCCN criteria (22,29,30), three studies used the AHPBA/SSO/SSAT criteria, (23,24,28) and the other seven studies diagnosed LAPC based on multidisciplinary review board or retrospective evaluation of pretreatment imaging. (12, 19-21, 25-27) The NCCN and AHPBA/SSO/SSAT definitions for LAPC vary mainly in the extent of vascular involvement (Table 1); definitions for LAPC were ambiguous in the other seven studies.…”

Section: Discussionmentioning

confidence: 99%

“…After screening of the abstracts, 30 studies were selected for full text assessment, of which 13 studies fulfilled the inclusion criteria. (12,(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) The excluded studies are presented in the webappendix, pages 2 and 3. Figure 1 presents the flowchart.…”

Section: Studiesmentioning

confidence: 99%

“…(19)(20)(21)(22)(23)(24)(25)(27)(28)(29)(30) Three studies used the NCCN criteria (22,29,30), and three studies used the AHPBA/SSO/SSAT criteria (23,24,28) to define LAPC. The other seven studies determined LAPC based on multidisciplinary review board or retrospective evaluation of pretreatment imaging.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…(19, 20, 22-24, 26, 29, 30) The pooled percentage of (chemo)radiation in a random effects model was 63·5% (95% CI: 43·3% -81·6%, I 2 = 90%). The modalities were stereotactic body radiotherapy (SBTR) in three studies (20,23,29), chemoradiation in three studies (22,24,30), and conventional radiation therapy in two studies. (19,26) No significant association was found across studies between the percentage of (chemo)radiation and OS (p=0·12) (webappendix, page 6).…”

Section: Subsequent Treatmentmentioning

confidence: 99%

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A patient-level meta-analysis of FOLFIRINOX for locally advanced pancreatic cancer.

et al. 2016

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Section: Discussionmentioning

confidence: 99%

Section: Studiesmentioning

confidence: 99%

Section: Study Characteristicsmentioning

confidence: 99%

Section: Subsequent Treatmentmentioning

confidence: 99%

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A patient-level meta-analysis of FOLFIRINOX for locally advanced pancreatic cancer.

et al. 2016

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“…The R0 resection rate was 87% and a median OS of 16 months was observed for those who underwent resection compared with 12 months for those who did not [75]. Despite a lack of radiation and inclusion of patients with locally advanced unresectable disease in these trials, the overall resection and R0 resection rates were high, indicating that chemotherapy alone has a role in the n eoadjuvant setting.Since FOLFIRINOX is superior to gemcitabine in good performance status patients [4] with metastatic pancreatic cancer, several retrospective studies have evaluated the use of this regimen in the neoadjuvant setting reporting resection rates ranging from 33 to 42% and R0 resection rates from 55 to 92% [21,53,91,[94][95][96]. Since there is significant toxicity associated with this regimen, investigators are exploring a modified FOLFIRINOX dose schedule as neoadjuvant therapy [95].…”

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confidence: 99%

The Role of Neoadjuvant Therapy in Pancreatic Cancer: A Review

et al. 2016

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Controversy remains regarding neoadjuvant approaches in the treatment of pancreatic cancer. Neoadjuvant therapy has several potential advantages over adjuvant therapy including earlier delivery of systemic treatment, in vivo assessment of response, increased resectability rate in borderline resectable patients and increased margin-negative resection rate. At present, there are no randomized data favoring neoadjuvant over adjuvant therapy and multiple neoadjuvant approaches are under investigation. Combination chemotherapy regimens including 5-fluorouracil, irinotecan and oxaliplatin, gemcitabine with or without abraxane, or docetaxel and capecitabine have been used in the neoadjuvant setting. Radiation and chemoradiation have also been incorporated into neoadjuvant strategies, and delivery of alternative fractionation regimens is being explored. This review provides an overview of neoadjuvant therapies for pancreatic cancer. KEYWORDS• 5-fluorouracilPancreatic adenocarcinoma is considered one of the most aggressive malignancies. Most patients are diagnosed with advanced stage disease and only 15-20% of patients are considered candidates for curative resection. An additional 5-10% is diagnosed with borderline resectable or locally advanced disease. Although surgical resection is considered the only potentially curative treatment, resection alone results in low cure rates with median overall survival (OS) rates of approximately 20 months [1,2]. Pancreatic cancer is biologically aggressive and lacks therapeutic agents that are effective against micrometastases. Even in patients who undergo complete surgical resection followed by adjuvant chemotherapy with or without radiation, the risk for systemic recurrence can be as high as 77%, and may be either locoregional or distant in nature [3].Response rates to adjuvant therapies are variable and there is no reliable method to identify which patients will respond to treatment. Nonetheless, some randomized studies demonstrate OS and disease-free survival advantages associated with adjuvant therapies for resectable pancreatic cancer [4,5].Unlike adjuvant therapy, a neoadjuvant treatment approach potentially allows for in vivo assessment of tumor response. In addition, the use of early systemic therapy prior to surgery allows treatment of radiographically undetectable metastatic disease in some patients. It has been reported that 670REviEW Russo, Ammori, Eads & Dorth future science group disease progression occurs in 45-74% following neoadjuvant chemoradiation [6][7][8][9] and 30-78% following neoadjuvant chemotherapy [10] . Noncurative surgery and its associated risks can be avoided in patients who demonstrate disease progression following n eoadjuvant therapy.Neoadjuvant treatment also has the potential to improve compliance [11] as adjuvant therapy is frequently delayed due to recovery from surgery. It is estimated that approximately 25% of patients undergoing curative resection for pancreatic cancer do not receive the planned postoperative treatment due to surgical co...

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Preoperative Modified FOLFIRINOX Treatment Followed by Capecitabine-Based Chemoradiation for Borderline Resectable Pancreatic Cancer

et al. 2016

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IMPORTANCE Although consensus statements support the preoperative treatment of borderline resectable pancreatic cancer, no prospective, quality-controlled, multicenter studies of this strategy have been conducted. Existing studies are retrospective and confounded by heterogeneity in patients studied, therapeutic algorithms used, and outcomes reported. OBJECTIVE To determine the feasibility of conducting studies of multimodality therapy for borderline resectable pancreatic cancer in the cooperative group setting. DESIGN, SETTING, AND PARTICIPANTS A prospective, multicenter, single-arm trial of a multimodality treatment regimen administered within a study framework using centralized quality control with the cooperation of 14 member institutions of the National Clinical Trials Network. Twenty-nine patients with biopsy-confirmed pancreatic cancer preregistered, and 23 patients with tumors who met centrally reviewed radiographic criteria registered. Twenty-two patients initiated therapy (median age, 64 years [range, 50–76 years]; 55% female). Patients registered between May 29, 2013, and February 7,2014. INTERVENTIONS Patients received modified FOLFIRINOX treatment (85 mg/m2 of oxaliplatin, 180 mg/m2 of irinotecan hydrochloride, 400 mg/m2 of leucovorin calcium, and then 2400 mg/m2 of 5-fluorouracil for 4 cycles) followed by 5.5 weeks of external-beam radiation (50.4 Gy delivered in 28 daily fractions) with capecitabine (825 mg/m2 orally twice daily) prior to pancreatectomy. MAIN OUTCOMES AND MEASURES Feasibility, defined by the accrual rate, the safety of the preoperative regimen, and the pancreatectomy rate. RESULTS The accrual rate of 2.6 patients per month was superior to the anticipated rate. Although 14 of the 22 patients (64% [95% CI, 41%–83%]) had grade 3 or higher adverse events, 15 of the 22 patients (68% [95% CI, 49%–88%]) underwent pancreatectomy. Of these 15 patients, 12 (80%) required vascular resection, 14 (93%) had microscopically negative margins, 5 (33%) had specimens that had less than 5% residual cancer cells, and 2 (13%) had specimens that had pathologic complete responses. The median overall survival of all patients was 21.7 months (95% CI, 15.7 to not reached) from registration. CONCLUSIONS AND RELEVANCE The successful completion of this collaborative study demonstrates the feasibility of conducting quality-controlled trials for this disease stage in the multi-institutional setting. The data generated by this study and the logistical elements that facilitated the trial's completion are currently being used to develop cooperative group trials with the goal of improving outcomes for this subset of patients. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01821612

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Outcomes with FOLFIRINOX for borderline resectable and locally unresectable pancreatic cancer

Cited by 171 publications

References 50 publications

A patient-level meta-analysis of FOLFIRINOX for locally advanced pancreatic cancer.

A patient-level meta-analysis of FOLFIRINOX for locally advanced pancreatic cancer.

The Role of Neoadjuvant Therapy in Pancreatic Cancer: A Review

Preoperative Modified FOLFIRINOX Treatment Followed by Capecitabine-Based Chemoradiation for Borderline Resectable Pancreatic Cancer

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