Oxaliplatin Plus 5-Fluorouracil and Folinic Acid (OFF) in Gemcitabine-Pretreated Advanced Pancreatic Cancer: A Phase II Study
Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Mansoura University, Mansoura, Egypt, . Journal of Gastrointestinal Cancer
(Impact Factor: 0.38).
04/2013; 44(3). DOI: 10.1007/s12029-013-9495-5
Despite median survival of less than 6 months, there is a significant proportion of advanced pancreatic cancer patients who progress on gemcitabine that remains fit, and these patients are candidates for second-line treatment.
The objective of this study is to evaluate the efficacy and safety of oxaliplatin plus 5-fluorouracil and folinic acid in patients with gemcitabine-pretreated advanced pancreatic cancer.
Patients and Methods
Thirty patients with advanced pancreatic cancer who were pretreated with gemcitabine received oxaliplatin (85 mg/m2) on days 1 and 15 followed by leucovorin (20 mg/m2) and 5-fluorouracil (500 mg/m2) on days 1, 8, and 15. The cycle was repeated every 3 weeks.
The majority of patients (80 %) had locally advanced disease. Median age was 63 years, and 60 % were males. The liver was the most common site of metastasis. Partial response was observed in 2 patients (6.7 %) and stable disease in 6 patients (20 %), while 12 patients progressed (40 %). Improved performance status was reported in 10 patients (33.3 %). The median duration of response was 13 weeks, and median overall survival was 22 weeks. There was no grade 4 toxicity apart from grade 4 neutropenia in 6.6 % of patients. Neutropenia (46.5 %) and neuropathy (43.2 %) were the most common toxicities, while hand–foot syndrome was the least frequent one (20 %). There were no treatment-related deaths. The 6-month survival rate was 30 %.
This regimen is feasible and active with an acceptable toxicity; however, further investigation in phase III trial is needed.
Available from: Volker Kaechele
- "Single agent docetaxel achieves response rates of up to 15 % as first line therapy of advanced PDAC[12,13], and has moderate activity as second line treatment of PDAC in retrospective analyses[14,15]. Oxaliplatin-based combination regimen show similar response rates as docetaxel161718. Several phase I/II studies confirmed the efficacy and safety of the combination of docetaxel plus oxaliplatin for different tumor entities192021. "
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The current study was conducted to examine the activity of a docetaxel/oxaliplatin (DocOx) combination as second line treatment for advanced pancreatic ductal adenocarcinoma (Trial registration: NCT00690300. Registered June 2, 2008) METHODS: DocOx is a prospective, multi-center, single arm, phase II trial using docetaxel (75 mg/m(2), 60 min, d 1) and oxaliplatin (80 mg/m(2), 120 min, d 2) in 21-day cycles. The treatment period was scheduled for up to 8 cycles. Primary endpoint was tumor response according to RECIST 1.0. Secondary endpoints were progression free survival, overall survival, safety/toxicity, quality of life and clinical benefit.
Data represent the intention to treat analysis of 44 patients with chemorefractory pancreatic cancer enrolled between 2008 and 2012 at five institutions in Germany. The primary endpoint of tumor response was achieved in 15.9 % of the patients (7 partial remissions, no complete remission), with a disease control rate of 48 % after the first two treatment cycles. Median progression free survival (PFS) was 1.82 months (CI 95 % 1.5-3.96 months) and median overall survival (OS) was 10.1 months (CI 95 % 5.1-14.1 months).
This single-arm trial demonstrates that the combination of docetaxel and oxaliplatin yields promising results for the treatment of advanced pancreatic ductal adenocarcinoma patients. Selected patients had particular benefit from this treatment as indicated by long PFS and OS times. Even after 8 cycles of treatment with DocOx a partial response was observed in 2 patients and stable disease was observed in another 6 patients. The data obtained with the DocOx protocol compare well with other second line protocols such as OFF (oxaliplatin, 5-FU, leucovorin). The DocOx regimen could be an interesting option for patients who received gemcitabine as first line treatment for metastatic pancreatic cancer.
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ABSTRACT: There remains uncertainty regarding the optimal second-line chemotherapy in advanced pancreatic ductal adenocarcinoma (PDAC). The current recommendation of 5-fluorouracil and oxaliplatin may not be relevant in current practice, as FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan and oxaliplatin) has become a more popular first line therapy in fit patients. The majority of studies in this setting are single-arm Phase II trials with significant heterogeneity of patient populations, treatments and outcomes. In this review, we sought to systematically review and synthesise all prospective data available for the second-line treatment of advanced PDAC.
Available from: Altaf Mohammed
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ABSTRACT: Pancreatic cancer (PC) remains one of the worst cancers, with almost uniform lethality. PC risk is associated with westernized diet, tobacco, alcohol, obesity, chronic pancreatitis, and family history of pancreatic cancer. New targeted agents and the use of various therapeutic combinations have yet to provide adequate treatments for patients with advanced cancer. To design better preventive and/or treatment strategies against PC, knowledge of PC pathogenesis at the molecular level is vital. With the advent of genetically modified animals, significant advances have been made in understanding the molecular biology and pathogenesis of PC. Currently, several clinical trials and preclinical evaluations are underway to investigate novel agents that target signaling defects in PC. An important consideration in evaluating novel drugs is determining whether an agent can reach the target in concentrations effective to treat the disease. Recently, we have reported evidence for chemoprevention of PC. Here, we provide a comprehensive review of current updates on molecularly targeted interventions, as well as dietary, phytochemical, immunoregulatory, and microenvironment-based approaches for the development of novel therapeutic and preventive regimens. Special attention is given to prevention and treatment in preclinical genetically engineered mouse studies and human clinical studies.
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