A long-term survivor of repeated inguinal nodes recurrence of papillary serous adenocarcinoma of CUP: case report

BACKGROUND: Tumor spread beyond the peritoneal cavity in cases of papillary serous adenocarcinoma of the unknown primary (CUP) is a rare late event and carries a poor prognosis. CASE PRESENTATION: A 71-year-old female was referred to our hospital because of a large right inguinal tumor with biopsy evidence of carcinoma as well as an elevated serum CA125 (cancer antigen 125). She underwent complete resection of the right inguinal tumor and multiple pelvic tumors, which involved the rectum, ovary and uterus. Pathological examination revealed the tumors to be metastases of a papillary serous adenocarcinoma with a psammoma body of CUP. On the 28th postoperative day, newly developed asymptomatic small left inguinal node metastases in the setting of a normal CA125 level were removed. Four and a half years after the primary resection, the CA125 level increased again and newly developed asymptomatic metastases were found in the right deep inguinal nodes and extirpated at that time. All surgical resections followed the modified FAM (5FU, Adriamycin; ADM, MMC) regimen, including protracted dairy oral administration of UFT or 5'-FDUR, Cimetidine and PSK (protein-bound polysaccharide K) as an immunomodulator or biological response modifier in conjunction with intermittent one-day continuous infusion (ADM+MMC) or intermittent single bolus injection of ADM+MMC. At present, the patient has been living in good health for almost 7 years with no evidence of relapse. CONCLUSION: Aggressive resection surgery followed by effective adjuvant chemotherapy is necessary for surviving long time without relapse of poorly prognostic patients with metastases outside of the abdominal cavity from peritoneal papillary serous adenocarcinomas

Strong Association of a Common Dihydropyrimidine Dehydrogenase Gene Polymorphism with Fluoropyrimidine-Related Toxicity in Cancer Patients

variations associated with enhanced drug toxicity. = 0.001; the attributable risk was 56.9%. Comparing tumor-type matched sets of samples, correlation of c.496A>G with toxicity was particularly present in patients with gastroesophageal and breast cancer, but did not reach significance in patients with colorectal malignancies. polymorphism strongly contributes to the occurrence of fluoropyrimidine-related drug adverse effects. Carriers of this variant could benefit from individual dose adjustment of the fluoropyrimidine drug or alternate therapies

Pharmacogenetics of telatinib, a VEGFR-2 and VEGFR-3 tyrosine kinase inhibitor, used in patients with solid tumors

Purpose Telatinib is an orally active small-molecule tyrosine kinase inhibitor of kinase insert domain receptor (KDR; VEGFR-2) and fms-related tyrosine kinase 4 (FLT4; VEGFR-3). This study aims at the identification of relationships between single nucleotide polymorphisms (SNPs) in genes encoding for transporter proteins and pharmacokinetic parameters in order to clarify the significant interpatient variability in drug exposure. In addition, the potential relationship between target receptor polymorphisms and toxicity of telatinib is explored. Methods Blood samples from 33 patients enrolled in a phase I dose-escalation study of telatinib were analyzed. For correlation with dose normalized AUC(0–12), ATP-binding cassette (ABC) B1 (ABCB1), ABCC1, and ABCG2 were the genes selected. For correlation with telatinib toxicity, selected genes were the drug target genes KDR and FLT4. Results No association between dose normalized AUC(0–12) and drug transporter protein polymorphisms was observed. In addition, no association between toxicity and KDR or FLT4 genotype or haplotype was seen. Conclusions Our pharmacogenetic analysis could not reveal a correlation between relevant gene polymorphisms and clinical and pharmacokinetic observations of telatinib

Phase I/II study of oxaliplatin with oral S-1 as first-line therapy for patients with metastatic colorectal cancer

Two phase II studies of S-1 monotherapy have shown promising response rates (RR) of 35–40% with good tolerability in patients with untreated metastatic colorectal cancer. To investigate the usefulness of S-1 plus oxaliplatin (SOX) as an alternative to infusional 5-fluorouracil/leucovorin plus oxaliplatin, the recommended dose (RD) of SOX was determined, and its safety and preliminary efficacy were evaluated in a phase I/II study. Oxaliplatin was administered at a dose of 100 mg m−2 (level 1) or 130 mg m−2 (level 2) on day 1, and S-1 (80–120) was given twice daily for 2 weeks followed by a 1-week rest. This schedule was repeated every 3 weeks. Level 2 was determined to be the RD. For the 28 patients who received the RD, the median treatment course was 6.5 cycles (2–14), RR of 50% (1 CR and 13 PR: 95% CI 31–69%), with a median progression-free survival of 196 days. Survival rate (1 year) was 79%. Peripheral neuropathy was observed in all patients but with no functional disorders. Major grade 3 or 4 adverse reactions at the RD were neutropaenia (14%), thrombocytopaenia (28%), and diarrhoea (3%). SOX regimen is effective and easily manageable without central vein access

An individual patient data meta-analysis of adjuvant therapy with uracil–tegafur (UFT) in patients with curatively resected rectal cancer

Uracil–Tegafur (UFT), an oral fluorinated pyrimidine chemotherapeutic agent, has been used for adjuvant chemotherapy in curatively resected colorectal cancer patients. Past trials and meta-analyses indicate that it is somewhat effective in extending survival of patients with rectal cancer. The objective of this study was to perform a reappraisal of randomised clinical trials conducted in this field. We designed an individual patient-based meta-analysis of relevant clinical trials to examine the benefit of UFT for curatively resected rectal cancer in terms of overall survival (OS), disease-free survival (DFS), and local relapse-free survival (LRFS). We analysed individual patient data of five adjuvant therapy randomised clinical trials for rectal cancer, which met the predetermined inclusion criteria. These five trials had a combined total of 2091 patients, UFT as adjuvant chemotherapy compared to surgery-alone, 5-year follow-up, intention-to-treat-based analytic strategy, and similar endpoints (OS and DFS). In a pooled analysis, UFT had significant advantage over surgery-alone in terms of both OS (hazard ratio, 0.82; 95% confidence interval (CI), 0.70–0.97; P=0.02) and DFS (hazard ratio, 0.73; 95%CI, 0.63–0.84; P<0.0001). This individual patient-based meta-analysis demonstrated that oral UFT significantly improves both OS and DFS in patients with curatively resected rectal cancer

Razvoj selektivnih biofarmaceutika iz glikoproteina E i I iz Herpes simplex virusa tipa 1 koji blokiraju neutralizaciju onkolitskih virusa posredovanu antitijelima

Future cancer therapies will be molecular cures. They will correct, block or destroy cancer cells by targeting molecular changes that lead to carcinogenesis. Destroying cancer cells can be done using oncolytic viruses. By blocking antibody mediated neutralization of oncolytic viruses, Herpes simplex virus type 1 glycoproteins E and I could be used in the adjuvant treatment of cancer for improving the chances of oncolytic viruses to kill cancer cells in vivo.Terapija karcinoma će u budućnosti biti na molekularnoj razini. Bit će moguće promijeniti, blokirati ili uništavati stanice ciljanim utjecanjem na molekularne promjene koje vode do karcinogeneze. Uništavanje stanica karcinoma moći će se ostvariti pomoću onkolitskih virusa. U pomoćnoj terapiji karcinoma moći će se koristiti glikoproteini E i I iz Herpes simplex virusa tipa 1 koji blokiraju neutralizaciju onkolitskih virusa posredovanu antitijelima, čime se povećavaju šanse da onkolitski virusi unište stanice karcinoma in vivo

Kidney- and Site-Selective Delivery of 5-Fluorouracil Utilizing the Absorption on the Kidney Surface in Rats

The present study was undertaken to elucidate the kidney- and site-selective delivery of 5-fluorouracil (5-FU) utilizing the absorption on the kidney surface in rats. An experimental system utilizing a cylindrical diffusion cell attached to the right kidney surface was established. After intravenous administration of 5-FU, the concentration of 5-FU in the right and left kidneys was almost the same and was rapidly eliminated. After right kidney surface application of 5-FU, however, the concentration of 5-FU in the right kidney was significantly higher than in the left kidney and other tissues. The 5-FU concentration in four sites of the right kidney after intravenous administration was almost the same. In contrast, 5-FU was site selectively delivered in the kidney after kidney surface application. The blood concentration of 5-FU was low (<1.7 μg/ml) until 120 min after kidney surface application. The maximum blood concentration of 5-FU after kidney surface application was much lower than after intravenous administration