Oxaliplatin related multiple focal nodular hyperplasia mimicking metastasis from a gastric cancer.

INTRODUCTION: The FOLFOX6 scheme is a combination drug chemotherapy that contains calcium leucovorin (folinic acid), fluorouracil, and oxaliplatin, the chronic use of chemotherapy with oxaliplatin can progress to focal nodular hyperplasia (FNH), which is a benign hepatic lesion. CASE REPORT: We present a case of a 26- year-old female diagnosed with an ovarian mixed germ cell tumor with extension to the peritoneum, treated with 12 cycles in 9 months with neoadjuvant chemotherapy FOLFOX 6 scheme and oophorectomy. A three-year follow-up CT showed three nodular and hypervascular hepatic lesions suspicious of metastatic disease; an MRI with liver-specific contrast confirmed the diagnosis of FNH. MANAGEMENT AND OUTCOME: The patient continued her follow-up without other treatment and metastatic disease. DISCUSSION: While most multiple liver lesions in a patient with cancer will be suspicious of metastasis, a careful drug history should be obtained, as an oxaliplatin-related side effect to develop FNH has been reported. MRI with liver-specific contrast has a positive predictive value of 95% because of the biliary excretion through OATP1B3 transporter, expressed in functional hepatocytes and overexpressed in some liver tumors such as FNH, so it should be performed when FNH is suspected.

Epithelial-Mesenchymal Transition and MicroRNAs in Colorectal Cancer Chemoresistance to FOLFOX.

The FOLFOX scheme, based on the association of 5-fluorouracil and oxaliplatin, is the most frequently indicated chemotherapy scheme for patients diagnosed with metastatic colorectal cancer. Nevertheless, development of chemoresistance is one of the major challenges associated with this disease. It has been reported that epithelial-mesenchymal transition (EMT) is implicated in microRNA-driven modulation of tumor cells response to 5-fluorouracil and oxaliplatin. Moreover, from pharmacogenomic research, it is known that overexpression of genes encoding dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), the DNA repair enzymes ERCC1, ERCC2, and XRCC1, and the phase 2 enzyme GSTP1 impair the response to FOLFOX. It has been observed that EMT is associated with overexpression of DPYD, TYMS, ERCC1, and GSTP1. In this review, we investigated the role of miRNAs as EMT promotors in tumor cells, and its potential effect on the upregulation of DPYD, TYMS, MTHFR, ERCC1, ERCC2, XRCC1, and GSTP1 expression, which would lead to resistance of CRC tumor cells to 5-fluorouracil and oxaliplatin. This constitutes a potential mechanism of epigenetic regulation involved in late-onset of acquired resistance in mCRC patients under FOLFOX chemotherapy. Expression of these biomarker microRNAs could serve as tools for personalized medicine, and as potential therapeutic targets in the future.

Impact of diabetes comorbidity on the efficacy and safety of FOLFOX first-line chemotherapy among patients with metastatic colorectal cancer: a pooled analysis of two phase-III studies.

BACKGROUND: The current analysis aims to provide an evaluation of the impact of diabetes mellitus (DM) on the efficacy and safety of first-line FOLFOX chemotherapy for patients with metastatic colorectal cancer (mCRC). METHODS: This is a pooled analysis of the comparator arms of two clinical trials (NCT00272051; NCT00305188) which evaluated first-line FOLFOX chemotherapy for patients with mCRC. The overall survival and progression-free survival according to patient subsets (non-diabetic and diabetic patients) were assessed through Kaplan-Meier analysis and log-rank testing. Propensity score matching was additionally conducted to account for heterogeneity in baseline characteristics of different subsets of patients. RESULTS: A total of 756 patients were enrolled in the current analysis; of which 64 patients have pre-existing DM while 692 patients were non-diabetic. Through Kaplan-Meier analysis, no evidence for overall or progression-free survival difference was found among the two patient subsets (P = 0.501; P = 0.960, respectively). Moreover, metformin treatment does not affect overall or progression-free survival among diabetic patients (P = 0.598; P = 0.748, respectively). Repetition of overall and progression-free survival assessment following propensity score matching does not reveal any differences. Comparing diabetic to non-diabetic patients, there were no differences between the two groups in terms of acute oxaliplatin-induced neurological symptoms including cold-induced dysthesia (P = 0.600), laryngeal dysthesia (P = 0.707), jaw pain (P = 0.743) or muscle pain (P = 0.506). Moreover, no difference was seen between the two groups in terms of the incidence of long-term oxaliplatin-induced paresthesia (P = 0.107), highest grade of paresthesia (P = 0.498) or rates of recovery from paresthesia (P = 0.268). Diabetic patients have, however, a shorter time to develop oxaliplatin-induced paresthesia (P = 0.024). CONCLUSION: DM does not seem to affect overall or progression-free survival of mCRC patients treated with first-line FOLFOX chemotherapy. Moreover, DM does not influence the incidence or severity of oxaliplatin-induced paresthesia in those patients while it might lead to a shorter time to develop oxaliplatin-induced paresthesia compared to non-diabetic patients.

Personalized dosing via pharmacokinetic monitoring of 5-fluorouracil might reduce toxicity in early- or late-stage colorectal cancer patients treated with infusional 5-fluorouracil-based chemotherapy regimens.

INTRODUCTION: Therapeutic plasma 5-fluorouracil (5-FU) levels are achieved in only 20% to 30% of patients with the current practice of administering 5-FU doses based on body surface area (BSA). Alternatively, 5-FU doses can be adjusted based on 5-FU pharmacokinetic (PK) monitoring. Although benefits of PK monitoring of 5-FU in metastatic colorectal cancer (CRC) have been reported, its utility among patients with early stage disease has not been reported. PATIENTS AND METHODS: We retrospectively examined the effect of 5-FU PK monitoring in 84 CRC patients (49 stage IV and 35 stage II/III) receiving mFOLFOX6 (modifiedFOLFOX6; modified 5-fluorouracil, leucovorin, oxaliplatin protocol) or mFOLFIRI (modified 5-fluorouracil, leucovorin, irinotecan protocol). Forty-six of the 84 patients received 5-FU doses based on BSA and 38 received doses that were adjusted with PK monitoring. 5-FU plasma levels were measured using a nanoparticle immunoassay method. RESULTS: 5-fluorouracil PK monitoring significantly improved disease-free survival in stage II/III patients (P = .0429). There was also a trend towards improved progression-free survival among stage IV patients who had their 5-FU levels PK-monitored (P = .16). Moreover, 5-FU PK monitoring significantly reduced (P = .0437) and delayed (P = .0144) adverse effects in stage II/III patients. Toxicity occurred after the second 5-FU dose in the BSA group and after the sixth to seventh dose in the PK monitoring group. In stage IV patients, the onset of toxicities was also delayed with PK monitoring (P = .0605). CONCLUSION: We provide evidence that PK monitoring of 5-FU is potentially beneficial for late stage and early stage CRC. These results contribute to the growing body of evidence regarding patient benefit when treatment decisions are based on the individual patient characteristics, in this case, a patients' 5-FU levels.

Fatal pneumonitis induced by oxaliplatin: description of three cases.

We describe 3 fatal cases of interstitial pneumonitis rapidly evolving to pulmonary fibrosis and death after the administration of oxaliplatin as part of the FOLFOX regimen. Due to the widespread use of oxaliplatin in oncology, clinicians should be aware of the risk and severity of oxalipatin-induced interstitial pneumonia.