Efficacy of chemotherapy for patients with metastatic or recurrent pancreatic adenosquamous carcinoma: A multicenter retrospective analysis

Background/objectivesPancreatic adenosquamous carcinoma (PASC) is a rare variant of pancreatic ductal adenocarcinoma (PDAC). The usual treatment for metastatic or recurrent PASC is systemic chemotherapy in accordance with the PDAC treatment strategy. This study aimed to investigate the efficacy of chemotherapy, especially the benefit of recent combination therapies, in patients with metastatic or recurrent PASC.MethodsWe conducted a multicenter retrospective analysis of 116 patients with metastatic or recurrent PASC treated with first-line chemotherapy between April 2001 and December 2017 at 24 Japanese institutions.ResultsCombination chemotherapies included gemcitabine + nab-paclitaxel (GnP, n = 28), fluorouracil/leucovorin + irinotecan + oxaliplatin (FFX, n = 10), gemcitabine + S-1 (GS, n = 10), and others (n = 9). Monotherapies included gemcitabine (n = 51) and S-1 (n = 8). The median overall survival (OS) was 6.5, 7.3, and 4.3 months for the whole cohort, the combination therapy group, and the monotherapy group, respectively. Multivariate analysis indicated that combination therapy showed a better trend in OS than monotherapy (hazard ratio = 0.68; 95% confidence interval, 0.38–1.20). GnP or FFX were selected in 58.7% of patients after FFX was approved in Japan, and revealed a median OS, median progression-free survival, and objective response rate of 7.3 months, 2.8 months, and 26.9% in GnP and 7.2 months, 2.3 months, and 20.0% in FFX respectively.ConclusionsThis study suggests that combination therapy may be more effective than monotherapy. GnP and FFX showed similar and clinically meaningful efficacy for patients with metastatic or recurrent PASC.     

Protocol digest of randomized phase II study of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel combination therapy for locally advanced pancreatic cancer: Japan clinical oncology group study (JCOG1407)

Gemcitabine is one of the standard treatments for locally advanced pancreatic cancer. Recent studies on metastatic pancreatic cancer have shown that combination chemotherapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) and gemcitabine plus nab-paclitaxel (GnP) prolonged the overall survival compared with gemcitabine alone. To select the most promising chemotherapy, a randomized phase II selection design trial was started in July 2016 to compare between modified FOLFIRINOX and GnP for patients with locally advanced pancreatic cancer. A total of 124 patients will be enrolled from 36 Japanese institutions within 2.5 years. The primary endpoint is the proportion of 1-year overall survival, and secondary endpoints are progression-free survival, distant metastasis-free survival, response rate in patients with target lesions, CA19-9 response, adverse events, treatment-related death, early death, grade 4 non-hematological toxicity, and dose intensity. This trial has been registered with the UMIN Clinical Trials Registry [http://www.umin.ac.jp/ctr/index.htm], and the registration number is UMIN000023143.     

FOLFIRINOX as second-line chemotherapy for advanced pancreatic cancer: A subset analysis of data from a nationwide multicenter observational study in Japan

BackgroundData on FOLFIRINOX as a second-line chemotherapy for advanced pancreatic cancer are limited. In the JASPAC06 study—a nationwide, multicenter, observational study—FOLFIRINOX for patients with unresectable or recurrent pancreatic cancer as any line of treatment showed favorable efficacy and safety in Japanese clinical practice.MethodsWe performed exploratory analyses of patients with unresectable or recurrent pancreatic cancer who received FOLFIRINOX as the second-line chemotherapy in Japanese clinical settings.ResultsOf the 399 evaluable patients, 44 were eligible for inclusion in the analysis. The patients’ characteristics were as follows: median age, 62 years; men, 26 (59%); Eastern Cooperative Oncology Group-Performance status 0/1, 30 (68%)/14 (32%); disease status, recurrent/local/metastatic: 4 (9%)/8 (18%)/32 (73%). The initial dose was reduced in 28 (64%) patients. The median time to treatment failure and number of cycles were 4.5 (range, 0.2–19.1) months and 6 cycles (range, 1–13 or more), respectively. The major grade 3/4 adverse events were neutropenia in 29 (66%), leucopenia in 17 (39%), anorexia in 7 (16%), febrile neutropenia in 5 (11%), and anemia in 5 (11%) patients. The median overall survival, progression-free survival, and 1-year survival rates were 10.3 (95% confidence interval [CI], 7.2–13.3), 4.1 (95% CI, 2.6–5.5) months, and 30%, respectively.ConclusionOur findings suggest that FOLFIRINOX as a second-line chemotherapy for advanced pancreatic cancer was effective in patients with a good performance status. It displayed toxicity similar to that observed with its use as a first-line treatment.     

Respect - A multicenter retrospective study on preoperative chemotherapy in locally advanced and borderline resectable pancreatic cancer

BackgroundNeoadjuvant chemotherapy has become a powerful tool to convert borderline resectable (BRPC) and locally advanced pancreatic cancers (LAPC) into a resectable scenario. However, data analyzing the optimal type of therapy are scarce. In the present multicenter retrospective study, we evaluated the influence of FOLFIRINOX (FFX) and gemcitabine (GEM)-based neoadjuvant therapy on patient prognosis.MethodsData on 239 patients from 7 centers across Europe was gathered using an online database. Patients having received their first cycle of chemotherapy for BRPC/LAPC before 06/2017, with a minimum follow-up of 12 months, were included in the intention-to-treat analysis.ResultsPatients treated with neoadjuvant FFX (n = 135) or gemcitabine + nab-paclitaxel (GNP) (n = 38) had significantly improved radiological response according to RECIST criteria as compared to single-agent GEM (n = 16), with a partial/complete response of 59.3%, 55.3% and 6.25% respectively (p = 0.001). Treatment with FFX (n = 135) and GNP (n = 38) resulted in higher resection rates compared to GEM (73.3%, 81.6% and 43.8%; p = 0.01 and p = 0.005). Regardless of regimen, patients who were resected had significantly prolonged overall survival compared to non-resected patients (p < 0.01). Complete pathological responses (ypT0 ypN0) were predominantly observed with FFX (p = 0.01). Adjuvant GNP in addition to successful neoadjuvant therapy and surgery resulted in a trend towards improved median survival as compared to postoperative observation (47.0 vs. 30.1 months, p = 0.06).ConclusionsRepresenting one of the largest studies published so far, our results reveal that patients with BRPC/LAPC should be offered either FFX or GNP to improve chances of resection and with this also survival.     

Modified FOLFIRINOX for unresectable locally advanced or metastatic gallbladder cancer,a comparison with GEMOX regimen

BackgroundThe first-line chemotherapy regimen for advanced gallbladder cancer (GBC) is gemcitabine plus platinum (GP), despite its efficacy is limited. The current investigation is a retrospective study to compare the safety and efficacy between the modified FOLFIRINOX (mFOLFIRINOX) and gemcitabine plus oxaliplatin (GEMOX) as the first-line chemotherapy for unresectable locally advanced or metastatic GBC.MethodsThe data of patients with unresectable locally advanced or metastatic GBC, who were treated with mFOLFIRINOX or GEMOX as the first-line therapy between April 2014 and April 2018 at Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, were retrieved. This retrospective study evaluated the clinical characteristics, survival outcomes and adverse events.ResultsA total of 44 patients (n=25 in mFOLFIRINOX, n=19 in GEMOX) were included. There were no significant differences between groups in baseline characteristics. The median progression free survival (mPFS) was 5.0 months in the mFOLFIRINOX group and 2.5 months in the GEMOX group [P=0.021; hazard ratio (HR), 0.499; 95% CI, 0.266 to 0.937]. The median overall survival (mOS) was 9.5 months in the mFOLFIRINOX group and 7.0 months in the GEMOX group (P=0.019; HR, 0.471; 95% CI, 0.239 to 0.929). Disease control rate (DCR) was 76.0% in the mFOLFIRINOX group and 47.4% in the GEMOX group (P=0.051). The rate of grade 3–4 adverse events was 48% in the mFOLFIRINOX group and 36.8% in the GEMOX group (P=0.459). The incidence of grade 3–4 neutropenia and diarrhea were more common in the mFOLFIRINOX group, while the incidence of grade 3–4 thrombocytopenia and peripheral neuropathy were more common in the GEMOX group.ConclusionsmFOLFIRINOX might improve the poor prognosis of unresectable locally advanced or metastatic GBC, and the results need to be further verified by prospective clinical studies.     

Clinical outcomes of first line FOLFIRINOX vs. gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer at the Yale Smilow Hospital System

BackgroundFOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GN) are established first line therapies for metastatic pancreatic cancer (MPC). There are, however, no randomized controlled trials comparing FFX and GN in the first line setting and real-world data on their comparative effectiveness is limited. We aimed to evaluate the outcomes of patients with MPC who were treated with first line FFX and GN and to further characterize dose modifications, discontinuation rates due to treatment toxicity, and rates of hospitalizations while on treatment.MethodsWe manually abstracted data from the electronic medical records (EMR) system at Yale Smilow Hospital and Smilow Cancer Hospital Care Centers for patients with MPC treated with at least one cycle of first line FFX or GN from January 2011 to April 2019. Patients who received prior neoadjuvant or adjuvant FFX or GN and adjuvant gemcitabine less than 6 months prior to metastatic recurrence were excluded. The median time to treatment discontinuation (TTD) and overall survival (OS) were determined using Kaplan-Meier method.ResultsWe identified 363 patients for analysis; 269 (74%) patients were treated with FFX and 94 (26%) with GN. Median TTD was 4.8 (IQR, 2.3–8.0) months in the FFX group compared to 3.4 (IQR, 1.3–5.7) months in the GN group (P=0.0037). Median OS was 11.3 (95% CI: 10.7–12.9) months in the FFX group and 7.0 (95% CI: 6.0–8.7) months in the GN group (P<0.001). Initial dose modifications occurred in 264 (98%) and 86 (91%) of FFX and GN treated patients, respectively (P=0.001). While on treatment, 56 (60%) of GN-treated patients had at least one hospitalization vs. 110 (41%) in the FFX-group (P=0.002). Treatment was discontinued due to chemotherapy toxicity in 26 (10%) and 14 (15%) among the FFX and GN cohorts, respectively (P=0.275).ConclusionsPatients treated with first line FFX had increased survival and TTD compared to patients treated with GN despite increased dose modifications and similar rates of treatment discontinuation due to treatment-related toxicity. GN-treated patients were older and more likely to be hospitalized while on treatment. Further study evaluating comparative effectiveness between these two regimens is warranted.     

Modified FOLFIRINOX for resected pancreatic cancer: Opportunities and challenges

Pancreatic cancer is one of the leading causes of cancer death worldwide.Adjuvant chemotherapy has been developed based on the experiences made with palliative chemotherapy, and advocated to improve long-term survival of patients with this disease. However, the optimal chemotherapeutic regimen remains controversial. Recently, Conroy et al demonstrated the impressive benefits of modified FOLFIRINOX over gemcitabine alone in the multicenter Partenariat de Recherche en Oncologie Digestive 24(PRODIGE-24) trial. The remarkable results mark a new milestone in treating resectable pancreatic cancer and have now changed the standard of care for this patient population. In this commentary, we discuss an issue of difference of tumor grade between the PRODIGE-24 trial and previous phase III trials. We also discuss potential biomarkers predicting therapeutic response to modified FOLFIRINOX. Finally,we summarize several ongoing clinical trials of replacing part of the FOLFIRINOX regimen with Xeloda/S-1/nanoliposomal irinotecan for pancreatic cancer.