A randomised phase II study of modified FOLFIRI.3 vs modified FOLFOX as second-line therapy in patients with gemcitabine-refractory advanced pancreatic cancer

Abstract

BACKGROUND: Only a few clinical trials have been conducted in patients with advanced pancreatic cancer after failure of first-line gemcitabine-based chemotherapy. Therefore, there is no current consensus on the treatment of these patients. We conducted a randomised phase II study of the modified FOLFIRI.3 (mFOLFIRI.3; a regimen combining 5-fluorouracil (5-FU), folinic acid, and irinotecan) and modified FOLFOX (mFOLFOX; a regimen combining folinic acid, 5-FU, and oxaliplatin) regimens as second-line treatments in patients with gemcitabine-refractory pancreatic cancer. METHODS: The primary end point was the 6-month overall survival rate. The mFOlFIRI.3 regimen consisted of irinotecan (70 mg m À2 ; days 1 and 3), leucovorin (400 mg m À2 ; day 1), and 5-FU (2000 mg m À2 ; days 1 and 2) every 2 weeks. The mFOLFOX regimen was composed of oxaliplatin (85 mg m À2 ; day 1), leucovorin (400 mg m À2 ; day 1), and 5-FU (2000 mg m À2 ; days 1 and 2) every 2 weeks. RESULTS: Sixty-one patients were randomised to mFOLFIRI.3 (n ¼ 31) or mFOLFOX (n ¼ 30) regimen. The six-month survival rates were 27% (95% confidence interval (CI) ¼ 13 -46%) and 30% (95% CI ¼ 15 -49%), respectively. The median overall survival periods were 16.6 and 14.9 weeks, respectively. Disease control was achieved in 23% (95% CI ¼ 10 -42%) and 17% patients (95% CI ¼ 6 -35%), respectively. The number of patients with at least one grade 3/4 toxicity was identical (11 patients, 38%) in both groups: neutropenia (7 patients under mFOLFIRI.3 regimen vs 6 patients under mFOLFOX regimen), asthaenia (1 vs 4), vomiting (3 in both), diarrhoea (2 vs 0), and mucositis (1 vs 2). CONCLUSION: Both mFOLFIRI.3 and mFOLFOX regimens were tolerated with manageable toxicity, offering modest activities as second-line treatments for patients with advanced pancreatic cancer, previously treated with gemcitabine.

The oncolytic adenovirus AdΔΔ enhances selective cancer cell killing in combination with DNA-damaging drugs in pancreatic cancer models

“…Nevertheless, antagonism with AdDD was not observed in any cell line, suggesting that the deletion of E1B19K might push the balance towards cell death. The degree of sensitization with the combination of AdDD and irinotecan, a topoisomerase I inhibitor, 34,44 was similar to that obtained in combination with gemcitabine in SUIT-2, PT45 and MIA PaCa-2 cells, with two-to fourfold reductions in EC 50 values. In contrast to gemcitabine, the enhancement of cell killing was independent of the sensitivity of each cell line to drug and might reflect the different mechanisms of action for these drugs.…”

An oncolytic adenovirus defective in pRb-binding (dl922–947) can efficiently eliminate pancreatic cancer cells and tumors in vivo in combination with 5-FU or gemcitabine

“…[2][3][4] Combining gemcitabine with 5-FU improved survival in certain patients, 5 whereas combinations with other cytotoxic drugs resulted in negligible survival benefits. [6][7][8] Improved therapies with greater efficacy and different mechanisms of action are therefore needed.…”

A phase 2 trial of personalized cytotoxic therapy based on tumor immunohistochemistry in previously treated metastatic pancreatic cancer patients

“…FOLFIRINOX is a standard first line regimen for mPC and the respective contributions of the individual therapeutic components (5FU, oxaliplatin, irinotecan) and tumor biomarkers (TOPO1, TS) to the efficacy of the regimen are not known. A number of pilot studies in mPC have suggested that FOLFIRI is active (23,24) and support for this hypothesis also comes from a recently completed study (NAPOLI-1), which established MM398 in combination with 5-FU as an effective 2nd line regimen (13). The therapeutic ratio of this combination could be enhanced if activity is increased in tumors with TOPO1 expression.…”