Mitomycin C and capecitabine: An additional option as an advanced line therapy in patients with metastatic colorectal cancer

BACKGROUND In recent years survival of patients with metastatic colorectal cancer(mCRC),though still limited,has improved significantly;clearly,when the disease becomes refractory to standard regimens,additional treatment options are needed.Studies have shown that mitomycin C(MMC),an antitumor antibiotic,and capecitabine,a precursor of 5-fluorouracil,may act synergistically in combination.The efficacy of MMC/capecitabine has been demonstrated in the first-line setting,but only a few small studies have tested it in the advanced-line setting,with contradictory results.received a median of 2 MMC/capecitabine cycles(range 0.5-9.0).Thirty-four patients(28.6%)experienced grade≥3 toxicity,including 2(1.7%)with grade 4;there was no drug-related mortality.The objective response rate was 0.8%,and the disease control rate,24.4%.Median progression-free survival(PFS)was 2.1 mo(range 0.2-20.3),and median overall survival,4.8 mo(range 0.2-27.5).The 6-month overall survival rate was 44%;8.7%of patients remained progression-free.Factors associated with longer PFS were lower gamma-glutamyl transferase level(P=0.030)and primary tumor location in the left colon(P=0.017).Factors associated with longer overall survival were lower gamma-glutamyl transferase level(P=0.022),left-colon tumor location(P=0.044),low-to-moderate histological grade(P=0.012),Eastern Cooperative Oncology Group performance status 0-1(P=0.036),and normal bilirubin level(P=0.047).CONCLUSION MMC/capecitabine is an active,available,and relatively safe regimen for use beyond standard lines of therapy in mCRC.Several clinical and laboratory parameters can identify patients more likely to benefit.

MicroRNAs as a potential prognostic factor in gastric cancer

AIM:To compare the microRNA (miR) profiles in the primary tumor of patients with recurrent and non-recurrent gastric cancer.METHODS:The study group included 45 patients who underwent curative gastrectomies from 1995 to 2005 without adjuvant or neoadjuvant therapy and for whom adequate tumor content was available.Total RNA was extracted from formalin-fixed paraffin-embedded tumor samples,preserving the small RNA fraction.Initial profiling using miR microarrays was performed to identify potential biomarkers of recurrence after resection.The expression of the differential miRs was later verified by quantitative real-time polymerase chain reaction (qRT-PCR).Findings were compared between patients who had a recurrence within 36 mo of surgery (bad-prognosis group,n=14,31%) and those who did not (good-prognosis group,n=31,69%).RESULTS:Three miRs,miR-451,miR-199a-3p and miR-195 were found to be differentially expressed in tumors from patients with good prognosis vs patients with bad prognosis (P<0.0002,0.0027 and 0.0046 respectively).High expression of each miR was associated with poorer prognosis for both recurrence and survival.Using miR-451,the positive predictive value for non-recurrence was 100% (13/13).The expression of the differential miRs was verified by qRT-PCR,showing high correlation to the microarray data and similar separation into prognosis groups.CONCLUSION:This study identified three miRs,miR-451,miR-199a-3p and miR-195 to be predictive of recurrence of gastric cancer.Of these,miR-451 had the strongest prognostic impact.

Octogenarian patients with colorectal cancer: Characterizing an emerging clinical entity

AIM To characterize colorectal cancer(CRC) in octogenarians as compared with younger patients.METHODS A single-center, retrospective cohort study which included patients diagnosed with CRC at the age of 80 years or older between 2008-2013. A control group included consecutive patients younger than 80 years diagnosed with CRC during the same period. Clinicopathological characteristics, treatment and outcome were compared between the groups. Fisher's exact test was used for dichotomous variables and χ2 was used for variables with more than two categories. Overall survival was assessed by Kaplan-Meier survival analysis, with the log-rank test. Cancer specific survival(CSS) and disease-free survival were assessed by the Cox proportional hazards model, with the Fine and Gray correction for non-cancer death as a competing risk.RESULTS The study included 350 patients, 175 patients in each group. Median follow-up was 40.2 mo(range 1.8-97.5). Several significant differences were noted. Octogenarians had a higher proportion of Ashkenazi ethnicity(64.8% vs 47.9%, P < 0.001), a higher rate of personal history of other malignancies(22.4% vs 13.7%, P = 0.035) and lower rates of family history of any cancer(36.6% vs 64.6%, P < 0.001) and family history of CRC(14.4% vs 27.3%, P = 0.006). CRC diagnosis by screening was less frequent in octogenarians(5.7% vs 20%, P < 0.001) and presentation with performance status(PS) of 0-1 was less common in octogenarians(71% vs 93.9%, P < 0.001). Octogenarians were more likely to have tumors located in the right colon(45.7% vs 34.3%, P = 0.029) and had a lower prevalence of well differentiated histology(10.4% vs 19.3%, P = 0.025). They received less treatment and treatment was less aggressive, both in patients with metastatic and non-metastatic disease, regardless of PS. Their 5-year CSS was worse(63.4% vs 77.6%, P = 0.009), both for metastatic(21% vs 43%, P = 0.03) and for non-metastatic disease(76% vs 88%, P = 0.028).CONCLUSION Octogenarians presented with several distinct characteristics and had worse outcome. Further research is warranted to better define this growing population.

Dose-Dense Regimen of Cisplatin and Infusional Fluorouracil in Advanced Gastric Cancer—A Single Institution Experience

Chemotherapy with continuous infusion of 5-fluorouracil and cisplatin in a monthly schedule is one of the most common regimens in the treatment of advanced gastric cancer. In this study, we evaluated the efficacy and safety of a dosedense administration of this regimen in this patient population. Sixty-six consecutive patients with previously untreated histologically confirmed unresectable or metastatic gastric adenocarcinoma were treated with a 2-hour infusion of cisplatin 100 mg/m2 followed by continuous infusion of 5-fluorouracil 1000 mg/m2/day for 5 days, every 21 days. The most common grade ≥3 toxicities were fatigue (42%), nausea/vomiting (30%) and leucopenia (12%). Four patients (6%) died from treatment-related toxicity. The response rate was 35%, the median progression-free survival was 4.3 months and the median survival was 5.9 months. In light of these results, the dose-dense approach seems to offer little, if any, benefit compared with the standard regimens.