Modified FOLFIRINOX compared to Gemcitabine & nab-Paclitaxel in advanced pancreatic ductal adenocarcinoma - results of a match-pair analysis

Background & objectives: FOLFIRINOX and gemcitabine plus nab-paclitaxel (GN) are the most commonly used regimens in advanced pancreatic ductal adenocarcinomas (PDACs). As there is limited data on comparison of these two regimens, the present study was aimed to compare survivals and tolerance for both regimens through a match-pair analysis. Methods: The data of 350 patients with metastatic and locally advanced PDAC, treated between January 2013 and December 2019, were retrieved. A 1:1 matching, using age and performance status, without replacement was performed by using nearest neighbour matching method. Results: A total of 260 patients (130 modified FOLFIRINOX and 130 GN) were matched. The median overall survival (OS) was 12.98 months [95% confidence interval (CI) 7.257-8.776 months] in modifications of FOLFIRINOX (mFOLFIRINOX) cohort and 12.06 months (95% CI 6.690-8.88 months) in GN group (P=0.080). The incidence of grade 3 and 4 infections, diarrhoea, oral mucositis, and fatigue was higher with mFOLFIRINOX. Patients who received second line therapy had improved OS as compared to those who did not (14.06 vs. 9.07 months, P<0.001). Interpretation & conclusions: GN and mFOLFIRINOX appear to have similar survival outcomes in an unselected match paired patient population with advanced PDAC. A markedly increased incidence of non-myelosuppressive grade 3 and grade 4 side-effects and lack of survival improvements suggest a need for nuanced use of the mFOLFIRINOX regimen. Administration of second-line chemotherapy improves OS in patients with advanced PDAC.

Folfirinox Neoadjuvant Therapy for Locally Advanced and Borderline Resectable Pancreatic Cancer - A Retrospective Study

Introduction: The management of borderline resectablepancreatic cancer has been heterogeneous and based onretrospective series. Historically, chemoradiotherapy had beenused to reduce the risk of a positive margin, local recurrence,and metastatic progression. Study was aimed to assess clinicaland pathologic efficacy of neoadjuvant FOLFIRINOX forlocally advanced (LAPC) and borderline resectable pancreaticcancer (BRPC).Material and Methods: In this retrospective study, patientsreceived neoadjuvant FOLFIRINOX for LAPC and BRPCwere included. Post-treatment patients achieving resectabilitywere referred for surgery, whereas unresectable patientscontinued chemotherapy. Clinical and pathological data wereretrospectively recorded.Results: The neoadjuvant group consisted of 29 PDACpatients, 16 with LAPC and 13 with BRPC who receivedneoadjuvant FOLFIRINOX. Reasons for non-resectabilityfollowing treatment included disease progression (10 patients),locally non-resectable disease (3 patients), and deteriorationof patient performance status (1 patient). Tumors size was1.87cm, the rate of lymphovascular invasion was 17.4%,the peripancreatic fat invasion was 52.2%, 22% of patientshad lymph node metastases. R0 resection was achieved inall patients. Evaluation of treatment response grading (TRG)demonstrated complete response (TRG 0) in 2 (15%) patients,and marked response (TRG 1) in 2 (15%) patients.Conclusion: Neoadjuvant FOLFIRINOX is aneffective, well-tolerated regimen for patientswith locally advanced and borderline resectable pancreaticcancer

Adjuvant Therapy of Pancreatic Cancer / 대한소화기암학회지

Pancreatic cancer is a lethal disease since curative resection is available in only 20% of patients at the initial diagnosis. Even after radical resection of the cancer, most patients experience recurrence. Therefore, many clinical trials have been attempted to prevent recurrence of pancreatic cancer. The key clinical studies about adjuvant therapy of pancreatic cancer and currently available regimens in Korea will be reviewed concisely according to the chemotherapy, radiation therapy, or both.

Neurotoxicidad orofacial en FOLFIRINOX: ¿Oxaliplatino o Irinotecán? / Oropharyngeal neurotoxicity in FOLFIRINOX: Oxaliplatin or Irinotecan?

El cáncer de páncreas resulta una de las patologías oncológicas con mayor índice de mortalidad en Argentina. Dadala importancia y prevalencia de esta afección, en los últimos años se han desarrollado varias alternativas de tratamiento que incluyen cirugía, radioterapia y quimioterapia endovenosa. El FOLFIRINOX es uno de los esquemas dequimioterapia de primera línea en los casos de neoadyuvancia y tumores avanzados. El esquema incluye dos drogasneurotóxicas: Oxaliplatino e Irinotecán. Se presentan dos casos de neurotoxicidad orofaríngea durante la infusiónde quimioterapia: un paciente masculino de 38 años y una femenina de 54. En ambos casos la neurotoxicidad fuereversible espontáneamente. Se plantea la disminución de la velocidad de infusión de oxaliplatino y la separación dela administración de ambas drogas como estrategia para la disminución de los efectos adversos(AU)

Pancreatic cancer is one of the oncological pathologies with the highest mortality rate in Argentina. Given the prevalenceof this condition, several treatments have been developed, including surgery, radiotherapy and intravenous chemotherapy.FOLFIRINOX is one of the first-line chemotherapy schemes in cases of neoadjuvant and advanced tumors. The schemeincludes two highly neurotoxic drugs: Oxaliplatin and Irinotecan. We present two cases of oropharyngeal neurotoxicityduring the chemotherapy infusion. A 38 years old male patient and 54 years old female patient. In both cases theoropharyngeal neurotoxicity was spontaneously reversible. The decrease in the rate of infusion of oxaliplatin and theseparation of the administration of both drugs was the strategy for the reduction of adverse effects(AU)

FOLFIRINOX as a first line therapy in locally advanced pancreatic cancer and borderline resectable pancreatic cancer: a Meta-analysis / 中华肝胆外科杂志

Objective To evaluate the efficacyof the first line chemotherapy FOLFIRINOX (5-Fu,Leucovorin calcium,Irinotecan,Oxaliplatin) as the treatment of pancreatic cancer.Methods Pertinent studies were identified from the PubMed,Cochrane Library and EMBASE.The outcomes were resection rate and radical (R0) resection rate were analyzed.Data were expressed as weighted pooled proportions with 95％ confidence intervals (95％ CI).Results There were thirteen studies with 408 patients with LAPC and BRPC included.After the treatment,42.0％ (95％ CI:28.0％ ～56.0％) tumorswere resected and 41.0％ (95％ CI:37.0％ ～45.0％) were underwentR0 resection,and median overall survival ranged from 15.5 to 34.5 months,median progression-free survival ranged from 10.0 to 17.8 months.Conclusion The meta-analysis shows that down-staging after first line FOLFIRINOX-based therapy is noticeable in patients with borderline resectable/unresectable PC,and the adverse events were in control.

Clinical efficacy of modified FOLFIRINOX as neoadjuvant chemotherapy for borderline resectable pancreatic cancer / 中华消化外科杂志

Objective To investigate the clinical efficacy of modified FOLFIRINOX as neoadjuvant chemotherapy for borderline resectable pancreatic cancer.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 28 patients diagnosed as borderline resectable pancreatic cancer who were admitted to the Tianjin Medical University Cancer Institute and Hospital between April 2013 and October 2015 were collected.Twenty-eight patients were treated with modified FOLFIRINOX (irinotecan 135 mg/m2,oxaliplatin 64 mg/m2,leucovorin 400 mg/m2,5-FU 2 400 mg/m2,repeat the regimen every 2 weeks) as neoadjuvant chemotherapy.After the completion of neoadjuvant chemotherapy,patients were evaluated operation feasibility and developed surgical planning in 3 weeks.Observation indicators:(1) Efficacy of neoadjuvant chemotherapy;(2) adverse events of neoadjuvant chemotherapy;(3) surgical and postoperative situations;(4)follow-up situations.Follow-up using outpatient examination,telephone interview and we-chat was performed to detect survival of patients up to January 2017.Measurement data with skewed distribution were described as median (range).The survival curve was drawn by Kaplan-Meier method and the survival analysis was done by Log-rank test.Results (1) Efficacy of neoadjuvant chemotherapy:28 patients received chemotherapy with a median cycle of 6 cycles (range,3-12 cycles).Chemotherapy reaction of 28 patients:14 had partial remission,10 had stable disease and 4 had progressive disease.(2) Adverse events of neoadjuvant chemotherapy:there were 22 adverse events of 28 patients during chemotherapy,including 15 with grade1-2 and 7 with grade 3-4.(3)Surgical and postoperative situations:of 28 patients,18 received radical resection for pancreatic cancer including 11 receiving pancreaticoduodenectomy,7 receiving distal pancreatectomy with splenectomy.Surgeries included 6 with portal vein and superior mesenteric vein resection and reconstruction,1 with coeliac trunk resection.Ten patients received R0 resection and 8 received R1 resection.Of 18 patients,8 with postoperative complications were improved by conservative treatment,including 2 with pancreatic fistula,1 with biliary fistula,3 with delayed gastric empty,1 with anastomotic hemorrhage,1 with lympha fistula.No patient received re-operation or died within 30 days postoperatively.Pathological TNM staging:2 patients were detected in stage Ⅰ-Ⅱ,14 in stage Ⅲ and 2 in stage Ⅳ.All the 18 patients received chemotherapy after operation.Ten patients without operation continued chemotherapy.(4) Following up:28 patients were followed up for 5-21 months with a median time of 13 months.Of the 15 died patients,5 received operation and 10 received no operation.The median progressionfree survival time and median overall survival time were 14 months and 19 months in the 18 operative patients,7 months and 11 months in the 10 non-operative patients,respectively,with statistically significant differences (x2=7.335,9.950,P＜0.05).Conclusions Modified FOLFIRINOX as neoadjuvant chemotherapy for borderline resectable pancreatic cancer is safe and effective,and patients can tolerate mild adverse reactions.Operable patients undergo surgeries after chemotherapy have relatively good outcome.

Clinical efficacy of modified FOLFIRINOX as neoadjuvant chemotherapy for borderline resectable pancreatic cancer / 中华消化外科杂志

Objective To investigate the clinical efficacy of modified FOLFIRINOX as neoadjuvant chemotherapy for borderline resectable pancreatic cancer.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 28 patients diagnosed as borderline resectable pancreatic cancer who were admitted to the Tianjin Medical University Cancer Institute and Hospital between April 2013 and October 2015 were collected.Twenty-eight patients were treated with modified FOLFIRINOX (irinotecan 135 mg/m2,oxaliplatin 64 mg/m2,leucovorin 400 mg/m2,5-FU 2 400 mg/m2,repeat the regimen every 2 weeks) as neoadjuvant chemotherapy.After the completion of neoadjuvant chemotherapy,patients were evaluated operation feasibility and developed surgical planning in 3 weeks.Observation indicators:(1) Efficacy of neoadjuvant chemotherapy;(2) adverse events of neoadjuvant chemotherapy;(3) surgical and postoperative situations;(4)follow-up situations.Follow-up using outpatient examination,telephone interview and we-chat was performed to detect survival of patients up to January 2017.Measurement data with skewed distribution were described as median (range).The survival curve was drawn by Kaplan-Meier method and the survival analysis was done by Log-rank test.Results (1) Efficacy of neoadjuvant chemotherapy:28 patients received chemotherapy with a median cycle of 6 cycles (range,3-12 cycles).Chemotherapy reaction of 28 patients:14 had partial remission,10 had stable disease and 4 had progressive disease.(2) Adverse events of neoadjuvant chemotherapy:there were 22 adverse events of 28 patients during chemotherapy,including 15 with grade1-2 and 7 with grade 3-4.(3)Surgical and postoperative situations:of 28 patients,18 received radical resection for pancreatic cancer including 11 receiving pancreaticoduodenectomy,7 receiving distal pancreatectomy with splenectomy.Surgeries included 6 with portal vein and superior mesenteric vein resection and reconstruction,1 with coeliac trunk resection.Ten patients received R0 resection and 8 received R1 resection.Of 18 patients,8 with postoperative complications were improved by conservative treatment,including 2 with pancreatic fistula,1 with biliary fistula,3 with delayed gastric empty,1 with anastomotic hemorrhage,1 with lympha fistula.No patient received re-operation or died within 30 days postoperatively.Pathological TNM staging:2 patients were detected in stage Ⅰ-Ⅱ,14 in stage Ⅲ and 2 in stage Ⅳ.All the 18 patients received chemotherapy after operation.Ten patients without operation continued chemotherapy.(4) Following up:28 patients were followed up for 5-21 months with a median time of 13 months.Of the 15 died patients,5 received operation and 10 received no operation.The median progressionfree survival time and median overall survival time were 14 months and 19 months in the 18 operative patients,7 months and 11 months in the 10 non-operative patients,respectively,with statistically significant differences (x2=7.335,9.950,P＜0.05).Conclusions Modified FOLFIRINOX as neoadjuvant chemotherapy for borderline resectable pancreatic cancer is safe and effective,and patients can tolerate mild adverse reactions.Operable patients undergo surgeries after chemotherapy have relatively good outcome.

Clinical application of FOLFIRINOX regimen for pancreatic cancer / 国际肿瘤学杂志

Clinical studies have confirmed the FOLFIRINOX regimen (oxaliplatin + irinotecan + fluorouracil + leucovorin) is an effective regimen for advanced pancreatic cancer patients with good performance status.Current clinical studies on FOLFIRINOX regimen mainly include neoadjuvant therapy for unresectable and borderline resectable pancreatic cancer and first-line therapy for locally advanced pancreatic cancer and metastatic pancreatic cancer,which improved patient's surgical resection opportunities and survival.In addition,the toxicity,safety of FOLFIRINOX regimen and effective population selection for FOLFIRINOX regimen are also the problems concerned by researchers.

Chemotherapy and Targeted Therapy with Management of Related Complications in Pancreatic Cancer / 대한췌담도학회지

Prognosis of pancreatic ductal adenocarcinoma is exceptionally poor because timely diagnosis in resectable stages is rare and there is no curative treatment for unresectable cases. Numerous researches to overcome these obstacles resulted in statistically significant but small progress. Recently two randomized controlled trial reported combination chemotherapy with 5-FU, irinotecan, leucovorin and oxaliplatin or Nab-paclitaxel plus gemcitabine was better survival than gemcitabine monotherapy. Many novel biological agents targeting the pancreatic cancer itself and surrounding micro-environment has been reported to be promising in preclinical investigations and phase 1/2 clinical studies. However, only erlotinib - a small molecular inhibitor of the epidermal growth factor receptor pathway - was approved for the targeted therapy for metastatic pancreatic cancer. In this review, we discuss briefly about recent advances in the combination chemotherapy and the targeted therapy including several complications related with these drugs.