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
BACKGROUND: 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. OBJECTIVE: 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/m(2)) on days 1 and 15 followed by leucovorin (20 mg/m(2)) and 5-fluorouracil (500 mg/m(2)) on days 1, 8, and 15. The cycle was repeated every 3 weeks. RESULTS: 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 %. CONCLUSION: This regimen is feasible and active with an acceptable toxicity; however, further investigation in phase III trial is needed.
- [Show abstract] [Hide abstract]
ABSTRACT: This study evaluates the maximum tolerated dose (MTD) and activity of mitomycin, docetaxel, and irinotecan (MDI) regimen on metastatic pancreatic adenocarcinoma, previously treated with gemcitabine-containing chemotherapy. Patients with less than 76 years, Karnofsky performance status > or = 60, and adequate bone marrow, kidney, and liver function were eligible for this trial. Treatment consisted of mitomycin 6 mg/m2 day 1, docetaxel and irinotecan on days 2 and 8 with escalating doses, every 4 weeks. Dose levels were level 1:30 and 70 mg/m2; level 2:30 and 100 mg/m2; level 3:30 and 85 mg/m2; and level 4:35 and 85 mg/m2. Dose-limiting toxicity (DLT) was defined as grade 4 neutropenia > 7 days, febrile neutropenia, grade 4 thrombocytopenia, nausea and vomiting, or diarrhea, grade > or = 3 nonhematological toxicity, or failure to recover to grade < or = 1 toxicity by day 43, occurring during the first cycle of chemotherapy. Between September 2001 and October 2002, 15 eligible patients, three of whom had been previously treated with two lines of chemotherapy, received 33 cycles of MDI. Toxicity consisted of grade 3 to 4 neutropenia in 23% of cycles, fatigue, diarrhea, and vomiting in 10% of cycles, and one toxic death. DLT was observed in 2 of 6 level 2 patients (one toxic death and one grade 3 fatigue), and 2 of 3 level 4 patients (one neutropenic fever and one grade 3 fatigue). Thirteen patients were assessable for response. No objective response was observed among patients treated with MTD or higher doses. Three patients had stable disease; all other patients had progressive disease. The median time to tumor progression and median survival was 1.7 and 6.1 months, respectively. The MTD was mitomycin 6 mg/m2 day one, and docetaxel 30 and irinotecan 85 mg/m2 days 2 and 8. This regimen is inactive in metastatic pancreatic cancer.Cancer Investigation 02/2004; 22(5):688-96. DOI:10.1081/CNV-200032929 · 2.22 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: This study evaluated the clinical activity and toxicity of combination chemotherapy with irinotecan and oxaliplatin in patients with advanced pancreatic cancer that had progressed despite > or =1 course of a gemcitabine-containing regimen. Thirty patients with metastatic pancreatic cancer and Karnofsky performance status > or =70 received oxaliplatin 60 mg/m2 on days 1 + 15 and irinotecan 60 mg/m2 on days 1 + 8 + 15 every 4 weeks. Patients were assessed on the basis of clinical benefit response, changes in serum tumour marker CA 19-9, objective tumour response, time to progressive disease (TTP), and survival. Six patients (20%) had clinical benefit response (median duration of 7.2 months). CA 19-9 levels were reduced > or =50% from baseline in 8 patients (26%) and remained stable in 8 patients. CT scans revealed that 3 patients (10%) had a partial response and 7 (23%) had stable disease. Two patients (7%) were down-staged and underwent surgery. Median TTP was 4.1 months, median survival was 5.9 months and the 1-year survival rate was 23.3%. The most serious adverse events were grade 3-4 leukopenia in 2 patients (6%), grade 3 neuropathy in 2 (6%) and grade 3 diarrhoea in 1 (3%). Chemotherapy with irinotecan and oxaliplatin is an active and well-tolerated combination in patients with advanced pre-treated pancreatic cancer.Oncology 10/2004; 67(2):93-7. DOI:10.1159/000080993 · 2.42 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: To investigate second-line chemotherapy in gemcitabine-pretreated patients with advanced or metastatic pancreatic cancer [(frequency, response, outcome, course of carbohydrate antigen 19-9 (CA 19-9)]. This retrospective study included all patients with advanced or metastatic pancreatic cancer (adenocarcinoma or carcinoma) treated with second-line chemotherapy in our center between 2000 and 2008. All patients received first-line chemotherapy with gemcitabine, and prior surgery or radiotherapy was permitted. We analyzed each chemotherapy protocol for second-line treatment, the number of cycles and the type of combination used. The primary endpoint was overall survival. Secondary endpoints included progression-free survival, response rate, grade 3-4 toxicity, dosage modifications and CA 19-9 course. A total of eighty patients (38%) underwent a second-line therapy among 206 patients who had initially received first-line treatment with a gemcitabine-based regimen. Median number of cycles was 4 (range: 1-12) and the median duration of treatment was 2.6 mo (range: 0.3-7.4). The overall disease control rate was 40.0%. The median overall survival and progression-free survival from the start of second-line therapy were 5.8 (95% CI: 4.1-6.6) and 3.4 mo (95% CI: 2.4-4.2), respectively. Toxicity was generally acceptable. Median overall survival of patients with a CA 19-9 level declining by more than 20% was 10.3 mo (95% CI: 4.5-11.6) vs 5.2 mo (95% CI: 4.0-6.4) for others (P = 0.008). A large proportion of patients could benefit from second-line therapy, and CA 19-9 allows efficient treatment monitoring both in first and second-line chemotherapy.World Journal of Gastroenterology 03/2012; 18(12):1357-64. DOI:10.3748/wjg.v18.i12.1357 · 2.37 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.
Hend A El-Hadaad