Influcence of Localization of Primary Tumor on Effectiveness of 5-Fluorouracil/Leucovorin Combined with Irinotecan and Oxaliplatin (FOLFIRINOX) in Patients with Metastatic Pancreatic Adenocarcinoma: A Retrospective Study.
ABSTRACT Metastatic pancreatic carcinoma is an incurable disease and gemcitabine remains the standard of care in first-line chemotherapy. Recently, fluorouracil/leucovorin combined with irinotecan and oxaliplatin (FOLFIRINOX) demonstrated their superiority in first-line therapy. The objective of this study was to determine the efficacy of FOLFIRINOX in either first- and second-line treatment and to compare its efficacy in regard to the location of the primary tumor.
We performed a retrospective analysis of clinical factors associated with patients' survival using a cohort of 42 patients treated by FOLFIRINOX in either first- or second-line (2006-2011) and a control cohort of 42 patients matched on sex and age without FOLFIRINOX treatment was obtained from a previous period of time (2001-2005).
The median follow-up was 10 months. The median overall survival was 10 months for the whole cohort and 10 and 12 months for patients treated at first- and second-line, respectively (p<0.05). In this cohort using a multivariate model, among classical prognosis factors, only primary location in the head was associated with poor outcome. The median overall survival was 8 months for patients with primary location in the head and 14 months for patients with primary location in the corpse or tail (p=0.02). In the gemcitabine cohort, the median follow-up was 8 months. Using a multivariate model, only performance status was associated with outcome. The median overall survival was 9 versus 6.5 months for patients with tumor, of the head versus tail or corpse tumor respectively (p<0.05).
This retrospective study suggests the same efficacy of FOLFIRINOX used either in first- or second- line therapy for pancreatic cancer. Importantly, FOLFIRINOX compared favorably to gemcitabine only for patients with tumor of the corpse or tail. Further prospective trials are warranted to evaluate the efficacy of FOLFIRINOX in patients with tumor of the head of the pancreas.
[Show abstract] [Hide abstract]
ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) can be divided into head, body and tail cancers according to the anatomy. Distinctions in tissue composition, vascularization and innervations have been clearly identified between the head and body/tail of the pancreas both in embryological development and in histopathology. To understand the postulated genotype difference, we present comprehensive information on two PDAC cell lines as typical representatives originating from pancreatic head and body/tail cancers, respectively. In the present review, we compare the difference between pancreatic head and body/tail cancers regarding clinical parameters and introducing an in vitro model. Increasing evidence has shown that tumors at different locations (head vs body/tail) display different clinical presentation (e.g. incidence, symptom), treatment efficiency (e.g. surgery, chemotherapy) and thus patient prognosis. However, the genetic or molecular diversity (e.g. mutations, microRNA) between the two subtypes of PDAC has not been elucidated so far. They present different chemo- and/or radio-resistance, extracellular matrix adhesion and invasiveness, as well as genetic profiles. Genetic and tumor biological diversity exists in PDAC according to the tumor localization.Hepatobiliary & pancreatic diseases international: HBPD INT 10/2013; 12(5):480-487. DOI:10.1016/S1499-3872(13)60076-4 · 1.17 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Background Pancreatic ductal adenocarcinoma (PDA) has a very poor prognosis. The combination of 5-fluorouracil, irinotecan and oxaliplatin (FOLFIRINOX) has been shown to improve outcomes, but can be associated with significant toxicity. Methods A retrospective review was performed of all patients with locally advanced or metastatic PDA treated with FOLFIRINOX at the Royal Marsden between November 2010 – November 2013. Efficacy, tolerability and potential prognostic factors were evaluated. Results Twenty-seven patients with metastatic PDA and 22 patients with locally advanced PDA were treated with FOLFIRINOX. Patients received a median of 9 cycles (range 1 – 26) of FOLFIRINOX. The overall response rate was 41%, and a further 35% of patients had stable disease. Thirty-five patients (71%) received FOLFIRINOX in the first-line setting, with a median progression-free survival and overall survival of 12.9 months and 18.4 months for patients with locally advanced disease; and 8.4 months and 12.2 months for patients with metastatic disease. The most frequently occurring grade 3-4 toxicities were neutropenia (29%), fatigue (18%), febrile neutropenia (14%), thromboembolism (12%) and thrombocytopenia (10%). In a univariate analysis, reduction in CA19-9 of > 50% (p < 0.001), normalisation of CA19-9 (p < 0.001), surgery post-FOLFIRINOX (p = 0.004) and use of prophylactic pegfilgrastim (p = 0.005) were prognostic for overall survival. Conclusion The efficacy and tolerability of FOLFIRINOX for PDA at our institution is similar to that reported in clinical trials. Careful selection of patients and monitoring of response (by CA19-9) and toxicities can help maximise advantage in this patient population.Clinical Colorectal Cancer 12/2014; 13(4). DOI:10.1016/j.clcc.2014.09.005 · 2.91 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: This study investigated the characteristics of oxaliplatin-related hypersensitivity reactions (HSR) and evaluated the efficacy of premedication and desensitization administration for controlling HSR in patients with gastrointestinal malignancy. This retrospective study includes oxaliplatin hypersensitivity cases reported to our in-hospital, adverse drug reaction monitoring system between May 2008 and April 2012. We analyzed administration histories of oxaliplatin and premedication treatments, chemotherapy cycle and severity of the initial HSR, and prophylactic measures and their outcomes in subsequent chemotherapy cycles. One hundred and seventy-three patients showed hypersensitivity to oxaliplatin-based chemotherapy. Oxaliplatin HSR developed after mean chemotherapy cycle 6.3 ± 0.3. Specifically, while HSR occurred at cycle 7.6 ± 0.3 in the case of patients previously unexposed to oxaliplatin-containing chemotherapy, it occurred at cycle 2.6 ± 0.3 in previously exposed patients. Of the 173 patients who exhibited HSR, premedication was administered in 134 patients and 71.6 % of them succeeded in preventing HSR. Desensitization was attempted in 38 patients, including 20 patients in whom premedication administration was unsuccessful, and 89 % of desensitized patients successfully underwent oxaliplatin chemotherapy without HSR. As severity of HSR increased, the success rate by premedication decreased and the percentage of patients that underwent desensitization increased. Attention should be paid to patients with any prior exposure to oxaliplatin, especially during early chemotherapy cycles. Given the high success rate of preventing HSR by desensitization administration and its apparent safety profile, we suggest that desensitization be considered as the first option for the treatment of grades 3 and 4 HSR cases.Cancer Chemotherapy and Pharmacology 04/2014; DOI:10.1007/s00280-014-2437-5 · 2.80 Impact Factor