Hepatic arterial infusion of gemcitabine-oxaliplatin in a large metastasis from colon cancer

Hepatic arterial infusion (HAI) of chemotherapy can be performed in cases of liver-confined metastatic disease,resulting in increased local drug concentrations.Here we report the case of a 61-year-old man who presented with an isolated large unresectable liver metastasis of colon cancer after failure of surgery and multiple administration of systemic chemotherapy.The patient was treated with a combination of gemcitabine and oxaliplatin using HAI.The tolerance was excellent and a radiological complete response was obtained after 8 cycles of HAI.The rationale for the use of gemcitabine and oxaliplatin as well as that for the combination of the 2 drugs is discussed in this paper.HAI of gemcitabine-oxaliplatin should be evaluated in further clinical trials.

FOLFIRI plus bevacizumab as a second-line therapy for metastatic intrahepatic cholangiocarcinoma

AIM:To evaluate the efficacy and tolerance of FOLFIRI plus bevacizumab treatment outcome as second-line treatment for metastatic intrahepatic cholangiocarcinoma.METHODS:Thirteen consecutive patients with metastatic intrahepatic cholangiocarcinoma who were refractory tofirst-line therapy consisting of gemcitabine plus oxaliplatinbased first-line chemotherapy given intravenously via intra-arterial infusion were treated with FOLFIRI[irinotecan(180 mg/m2 i.v.over 90 min)concurrently with folinic acid(400 mg/m2 i.v.over 120 min)followed by fluorouracil(400 mg/m2 i.v.bolus)then fluorouracil 2400 mg/m2 intravenous infusion over 46 h]and bevacizumab(5mg/kg)every 2 wk.Tumor response was evaluated by computed tomography scan every 4 cycles.RESULTS:The best tumor responses using response evaluation criteria in solid tumor criteria were:complete response for 1 patient,partial response for 4 patients,and stable disease for 6 patients after 6 mo of follow-up.The response rate was 38.4%(95%CI:12.5-89)and the disease control rate was 84.5%(95%CI:42-100).Seven deaths occurred at the time of analysis,progression free survival was 8 mo(95%CI:7-16),and median overall survival was 20 mo(95%CI:8-48).No grade 4toxic events were observed.Four grade 3 hematological toxicities and one grade 3 digestive toxicity occurred.An adaptive reduction in chemotherapy dosage was required in 2 patients due to hematological toxicity,and a delay in chemotherapy cycles was required for 3 patients.CONCLUSION:FOLFIRI plus bevacizumab combination treatment showed promising efficacy and safety as second-line treatment for metastatic intrahepatic cholangiocarcinoma after failure of the first-line treatment of gemcitabine plus oxaliplatin chemotherapy.

Folfirinox in elderly patients with pancreatic or colorectal cancer-tolerance and efficacy

AIM To study the tolerance and the efficiency of FOLFIRINOX in elderly patients diagnosed with colorectal or pancreatic cancer.METHODS This retrospective study included elderly patients aged over 70 years of age treated at Georges-Francois Leclerc Center by FOLFIRINOX for histological proved colorectal or pancreatic cancer between January 2009 and January 2015. Chemotheapy regimen consisted of oxaliplatin(85 mg/m2 in over 120 min) followed by leucovorin(400 mg/m2 in over 120 min), with the addition, after 30 min of irinotecan(180 mg/m2 in over 90 min) then 5 fluorouracil(5FU)(400 mg/m2 administred intravenous bolus), followed by 5FU(2400 mg/m2 intraveinous infusion over 46 h) repeated every 2 wk. Geriatric parameters were recorded at the beginning. Toxicities were evaluated with the Common Terminology Criteria for Adverse Events 4.03. Tumor response was evaluated by CT scan. Treatment continued until disease progression, unacceptable toxicities or patient refusal.RESULTS Fifty-two patients aged from 70 to 87 years were treated by FOLFIRINOX, 34 had colorectal cancer and 18 had pancreatic cancer. Most of them were in good general condition, 82.7% had a 0-1 performance status and 61.5% had a Charlson Comorbidity Index < 10. The most frequent severe toxicities were neutropenia(17 patients, n = 32.7%) and diarrhea(35 patients n = 67.3%); 10 of the case of neutropenia and 5 of diarrhea registered a grade 4 toxicity. Thirty-nine patients(75%) initially received an adapted dose of chemotherapy. The dosage was adjusted for 26% of patients during the course of treatment. Tumor response evaluated by RECIST criteria showed a controlled disease for 25 patients(48.1%), a stable disease for 13 and a partial response for 12 patients. Time under treatment was higher for colorectal cancer with a median time of 2.44 mo(95%CI: 1.61-3.25). Overall survival was 43.88 mo for colorectal cancer and 12.51 mo for pancreatic cancer. In univariate or multivariate analysis, none of geriatric parameters were linked to overall survival. Only the type of tumor(pancreatic/colorectal) was linked in both analysis.CONCLUSION For people over 70 years old, FOLFIRINOX regimen seems to induce manageable toxicities but similar, even higher, median survival rates compared to younger people.

Prognostic value of chemotherapy-induced hematological toxicity in metastatic colorectal cancer patients

AIM: To establish whether chemotherapy-induced neutropenia is predictive of better outcome in patients with metastatic colorectal cancer (mCRC).

Retrospective evaluation of FOLFIRI3 alone or in combination with bevacizumab or aflibercept in metastatic colorectal cancer

BACKGROUND The treatment of metastatic colorectal cancer(mCRC) relies of chemotherapy. The efficacy of the standard FOLFIRI-therapy could be improved by a modification of the regimen by splitting the dose of irinotecan on day 1 and day 3 in the FOLFIRI3 regimen.AIM To determine safety and efficacy of FOLFIRI3 regimen.METHODS This is a monocentric retrospective study evaluating the efficacy and safety of the FOLFIRI3 regimen given alone or in combination with bevacizumab or aflibercept in patients with previously treated mCRC.RESULTS One hundred and fifty-three consecutive patients were included(18 treated with FOLFIRI3, 99 with FOLFIRI3 plus bevacizumab and 36 with FOLFIRI3 plus aflibercept). The overall response rate(ORR) and disease control rate were 51%and 62%, respectively. Similar ORRs were observed in all 3 cohorts. Median progression-free survival(PFS) and overall survival(OS) were 3.9 mo(95%CI:3.2-4.9) and 9.4 mo(95%CI: 6.6-12), respectively. Median PFS and OS values were improved in the FOLFIRI3 plus aflibercept group. The most common grade 3-4 adverse events were diarrhoea(21.6%) and neutropenia(11.8%), and these toxicities were more frequent in the FOLFIRI3 plus aflibercept group. According to the multivariate Cox proportional model, previous surgery of metastasis andaflibercept were associated with outcomes.CONCLUSION The modification of the FOLFIRI regimen impacted treatment response of mCRC patients. The addition of an antiangiogenic agent, in particular aflibercept,enhanced the clinical benefit and improved survival.

Safety and efficacy of a docetaxel-5FU-oxaliplatin regimen with or without trastuzumab in neoadjuvant treatment of localized gastric or gastroesophageal junction cancer: A retrospective study

BACKGROUND Triplet chemotherapy,with docetaxel-5FU-oxaliplatin FLOT regimen recently became the standard perioperative treatment for localized gastric cancer(GC).An adapted regimen called TeFOX was recently tested in metastatic setting and gave promising results.AIM To determine safety and efficacy of TeFOX perioperative regimen.METHODS This monocentric retrospective study aims to test efficacy and safety of the perioperative TeFOX regimen given alone or in combination with trastuzumab in patients with localized GC.TeFOX consist in docetaxel(50 mg/m^2)with oxaliplatin 85 mg/m^2 and and leucovorin(400mg/m^2^)5 FU bolus(400mg/m^2)on day 1,followed by continuous infusion of 5FU for 46h(2400mg/m^2)every 2 wk.RESULTS Thirty-three consecutive patients were included in this retrospective study.Eighteen patients have a gastroesophageal junction cancer and 11 have a GC.Median follow-up of surviving patients was 32 mo.R0 resection was obtained in 30(91)patients.Twelve patients(36)had a pathological complete response and 8(24)patients a nearly complete pathological response.Median OS and PFS were not reached at data base lock.We have observed 6 metastatic relapses and 1 localized relapse.No relapse was observed in patients with pathological complete responses.The most common grade 3-4 adverse events were peripheral neuropathy(21)and asthenia(20).CONCLUSION TeFOX regimen could be safely administrated in perioperative treatment of localized GC.TeFOX and the FLOT regimen have comparable efficacy and safety profiles.