Clinical benefits of cetuximab retreatment in patients with metastatic colorectal (mCRC) have been reported. In the present study, the effect of cetuximab retreatment on predictive markers was investigated by evaluating the clinical benefit of initial cetuximab treatment prior to cetuximab retreatment. Between November 2012 and March 2017, 14 patients with KRAS proto-oncogene GTPase exon 2 wild-type mCRC who exhibited a clinical benefit (confirmed stable disease for at least 6 months or a clinical response) to an initial cetuximab-based regimen, who received multiple lines of chemotherapy following disease progression and ultimately received a second cetuximab and irinotecan regimen, were retrospectively analyzed. For retreatment, patients received bi-weekly irinotecan (120–150 mg/m2) combined with cetuximab (400 mg/m2 as an initial dose, followed by 250 mg/m2, weekly). The median age of the 14 patients (11 males, 3 females) was 68 years (32–77). The median progression-free survival (PFS) following prior cetuximab-based therapy was 6.6 months (range, 4.1–18.4). Initial cetuximab treatment was administered as a first-line treatment in 11 patients, a second-line treatment in 1 patient and a third-line treatment in 2 patients. The median interval time between the last cycle of initial cetuximab-based therapy and the first cycle of cetuximab retreatment was 13.1 months (range, 6.0–37.1). The objective response rate of cetuximab retreatment was 21.4% and the median PFS was 4.4 months (95% confidence interval, 1.4–5.6). The Spearman's correlation coefficient for the PFS following retreatment and duration of initial cetuximab-based regimens demonstrated a more marked correlation compared with that between the PFS following retreatment and the interval time between the two regimens (r=0.45, P=0.11 vs. r=0.08, P=0.79). Cetuximab retreatment may provide clinical benefit to patients with mCRC who were good responders with longer periods of initial cetuximab-based therapy.
A patient with an Edmondson type I-II hepatocellular carcinoma had, at celiac angiography, a poor arterial supply but a rich portal supply as observed at percutaneous transhepatic portography, an observation not previously reported in this disease. The importance of demonstrating the vascular supply of the tumor previous to planned intravascular treatment is obvious.
Predictive factors of cetuximab efficacy for metastatic colorectal cancer (mCRC) have not been sufficiently revealed. The present study aimed to explore new predictors. A total of 30 patients with KRAS exon 2 wild-type unresectable mCRC, who had been treated with cetuximab-based regimen as first-line therapy, were retrospectively analyzed. We assessed whether gender, age, primary tumor site, RAS genotype, the Eastern Cooperative Oncology Group Performance Status (ECOG PS), metastatic status, histological grade, carcinoembryonic antigen (CEA), treatment regimen, and oxaliplatin-based adjuvant chemotherapy at baseline were associated with cetuximab efficacy. Progression-free survival (PFS) and objective response rate (ORR) were evaluated and statistically analyzed. Analysis of PFS revealed that left-sided tumor and good PS had relevance to good results. PFS among patients with left-sided CRC was longer than that among those with right-sided CRC (median, 10.6 and 3.5 months, respectively). Patients with a PS of 0 -1 experienced significantly longer PFS than those with a PS of 2 -3 (median, 8.6 versus 1.3 months, respectively). In analysis of ORR, high histological grade and serum CEA level showed interaction with good effect. Patients with histological grade I/II cancer experienced better ORR than those with histological grade III/IV cancer (76% versus 20%, respectively). ORR among patients with serum CEA level higher than 5.0 ng/ml was significantly higher than that among those with lower serum levels (88% versus 38%, respectively). ECOG PS, tumor location, histological grade, and serum CEA level at baseline might be useful predictors of cetuximab efficacy in the first-line treatment of mCRC.
578 Background: BV is widely used for treatment of metastatic colorectal cancer (mCRC) patients. Although BV was often administrated to mCRC patients in combination with oxaliplatin, optimal schedule remains unclear. Many mCRC patients cannot continue to use oxalipatin because of cumulative neurotoxity, which decreases patient's QOL and motivation.We postulated that modification of oxaliplatin schedule would improve TTF in intermittent oxaliplatin usage. Therefore, we planned to use BV with original OPTIMOX1 adiministration schedule; modified oxaliplatin dose (85 mg/m3). Methods: Patients were enrolled with the criteria excluding neuropathy, PS ≥ 1, or no previous usage of oxaliplatin and BV, and then were received modified FOLFOX6 regimen (L-OHP 85 mg/m2, l-LV 200 mg/m2, 5-FU 400 mg/m2 bolus, 5-FU 2,400 mg/m2 46h continuous infusion) plus BV (5 mg/kg) q2wks x 6 cycles, followed sLV5FU2 (omit L-OHP) plus BV x 12 cycles regimen. After that, oxaliplatin reintroduction was done and mFOLFOX6 plus BV regimen was continued until PD. The evaluation of antitumor effect was done according to RECIST Criteria. Results: 40 patients accrued this trial. Median age was 65 years old. PS0: 89.5%, male: 75%, female: 25%, colon: 65.8%, rectal: 31.6%,colon + rectal: 2.6%. During initial 6 cycles of chemotherapy, 90% patients could continue chemotherapy. Response rate was 50%, and clinical benefit (including SD) was 92.1%. During Intial 6 cycles, G3 neuropathy occurred 2.6%, and G2 were 5%. Most frequent toxicity (≥G3) was neutropenia (30.8%) and anorexia (5.3%). One patient could complete the scheduled regimen. This patient continued mFOLFOX6+BV for 12 cycles after reintroduction keeping with PS 0, and was received FOLFIRI+BV regimen as second-line chemotherapy. Further information are under examination. Conclusions: This administration schedule was well tolerated and could continue chemotherapy longer than usual method. sLV5FU2+BV regimen was not affected reintroduction rate and progression free survival. BV with mOPTIMOX1 regimen can be expected to become a good treatment options for mCRC patients. No significant financial relationships to disclose.
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