• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1845-1849
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• 2014

Background: There is no standard treatment for patients with colorectal cancer (CRC) progressing after irinotecan and oxaliplatin treatment. Here we aimed to retrospectively evaluate the efficacy and tolerability of raltitrexed in combination with oral 5-fluoropyrimidine (uracil tegafur-UFT) or mitomycin C as salvage therapy in mCRC patients. Materials and Methods: A total of 62 patients who had received raltitrexed combined with UFT or mitomycin C were identified between December 2008 and June 2013. They were given raltitrexed 2.6 $mg/m^2$ (max 5 mg) i.v. on day 1 in combination with either oral UFT 500 mg/day on days 1-14 every 3 weeks (group A) or mitomycin C 6 $mg/m^2$ i.v. on day every 3 weeks (group B). Results: Forty-two patients (67.7%) were in group A and 20 (32.2%) in group B. In 15 patients (24%) grade 3/4 toxicity was observed, resulting in dose reduction, and in 13 patients (20.9%) dose delay was necessary. The median progression free survival (PFS) was 3 months (95%CI 2.65-3.34) and median overall survival (OS) was 6 months (95%CI 2.09-9.90) in the whole group. Median PFS was 3 months (95%CI 2.60-3.39) in group A vs 3 months (95%CI 1.64-4.35) in group B (p=0.90). Median OS was 6 months (95%CI 2.47-9.53) in group A vs 12 months (95%CI 2.83-21.1) in group B (p=0.46). Conclusions: The combination of raltitrexed with UFT or mitomycin C seem to be a salvage therapy option due to safety profile and moderate clinical activity in heavily-pretreated mCRC patients.

• Journal of Pharmaceutical Investigation
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• v.34 no.3
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• pp.161-168
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• 2004

5-Fluorouracil (5-FU) is an antimetabolite anticancer agent active against many types of solid tumors. Tegafur (TF), a prodrug of 5-FU, is frequently used in combination with uracil as dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine. We studied the stability of 5-FU and TF in biological fluids of rats and determined their bioavailability (BA) and excretion into bile, and urine. The drug concentrations were analyzed by an HPLC method. At room temperature, there was a 14-30% decrease in the concentration of 5-FU and TF in bile, urine, and plasma specimen at 10 and $100\;{\mu}g/ml$ over 240 min. No significant difference was noted among the sample types or between two different concentrations of 10 and $100{\mu}g/ml$. The decrease in drug concentration was significantly less in samples kept on ice (6-12%) for both drugs. These data indicate that biological fluid samples containing 5-FU or TF in plasma, urine, or bile should be placed on ice during the sample collection. Following these storage guidelines, samples were collected after administration 50 mg/kg of each drug via i.v. or oral route. BA was 1.5 folds greater for TF (60%) than that of 5-FU (42%). Approximately 0.52 and 3.3% of the i.v. doses of 5-FU and TF was excreted into bile, respectively. Renal clearance of 5-FU was about 16% of its total body clearance. These results suggest that instability of 5-FU and TF in biological fluids should be considered in pharmacokinetic or pharmacogenomic studies.

• Korean Journal of Head & Neck Oncology
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• v.10 no.1
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• pp.74-79
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• 1994

A Phase II study of UFT which is a mixture of Tegafur and Uracil was conducted in two institutions during past two years. Ninty-four patients of head and neck squamous cell carcinoma entered this trial, of which sixty-eight were evaluated. Among those, thirty-six cases were previously untreated and thirty-two cases were recurrent UFT was administrated orally at a daily dose of $400mg/m^2$ for eight weeks. The results were as following: 1) Overall response was 30.88%, but for 38.36% for 36 cases of the untreated cases, 21.88% for 32 cases of recurrent cases. 2) UFT was more effective in early stage and well differentiated squamous cell carcinoma and UFT tended to reduce the tumor size maximally at fourth or fifth week 3) There was no serious side effects except mild gastrointestinal disturbances such as nausea and vomiting, which were recovered immediately after stop or reducing a daily dose. Therefore, UFT therapy is clinically effective for head and neck squamous cell carcinoma and also may be useful for combination or palliative chemotherapy because of mild side effects.

• Radiation Oncology Journal
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• v.30 no.3
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• pp.99-107
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• 2012

Purpose: The aim of this study was to identify clinical predictive factors for tumor response after preoperative chemoradiotherapy (CRT) in rectal cancer. Materials and Methods: The study involved 51 patients who underwent preoperative CRT followed by surgery between January 2005 and February 2012. Radiotherapy was delivered to the whole pelvis at a dose of 45 Gy in 25 fractions, followed by a boost of 5.4 Gy in 3 fractions to the primary tumor with 5 fractions per week. Three different chemotherapy regimens were used (5-fluorouracil and leucovorin, capecitabine, or tegafur/uracil). Tumor responses to preoperative CRT were assessed in terms of tumor downstaging and pathologic complete response (ypCR). Statistical analyses were performed to identify clinical factors associated with pathologic tumor response. Results: Tumor downstaging was observed in 28 patients (54.9%), whereas ypCR was observed in 6 patients (11.8%). Multivariate analysis found that predictors of downstaging was pretreatment relative lymphocyte count (p = 0.023) and that none of clinical factors was significantly associated with ypCR. Conclusion: Pretreatment relative lymphocyte count (%) has a significant impact on the pathologic tumor response (tumor downstaging) after preoperative CRT for locally advanced rectal cancer. Enhancement of lymphocyte-mediated immune reactions may improve the effect of preoperative CRT for rectal cancer.

• Journal of Gastric Cancer
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• v.16 no.2
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• pp.115-119
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• 2016

We report the case of a patient with gastric adenocarcinoma with multiple liver metastases. This patient showed complete remission for more than 68 months after S-1/cisplatin combination chemotherapy and radical total gastrectomy. The patient, a 63-year-old man, presented with dyspepsia and difficulty in swallowing. Endoscopic findings showed a huge ulcero-infiltrative mass at the lesser curvature of the mid-body, extending to the distal esophagus. Biopsy revealed a poorly differentiated tubular adenocarcinoma. An abdominal computed tomography scan demonstrated multiple hepatic metastases. S-1/cisplatin combination chemotherapy was initiated, and following completion of six cycles of chemotherapy, the gastric masses and hepatic metastatic lesions had disappeared on abdominal computed tomography. Radical total gastrectomy and D2 lymphadenectomy combined with splenectomy were performed. The patient underwent three cycles of S-1/cisplatin combination chemotherapy followed by tegafur-uracil therapy for 1 year. He remained in complete remission for more than 68 months after surgery.

• Radiation Oncology Journal
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• v.24 no.3
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• pp.157-163
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• 2006

[ $\underline{Purpose}$ ]: To evaluate the role of postoperative adjuvant chemoradiotherapy in rectal cancer, we retrospectively analyzed the treatment outcome of patients with rectal cancer taken curative surgical resection and postoperative adjuvant chemoradiotherapy. $\underline{Materials\;and\;Methods}$: A total 46 patients with AJCC stage II and III carcinoma of rectum were treated with curative surgical resection and postoperative adjuvant chemoradiotherapy. T3 and T4 stage were 38 and 8 patients, respectively. N0, N1, and N2 stage were 12, 16, 18 patients, respectively. Forty patients received bolus infusions of 5-fluorouracil ($500\;mg/m^2/day$) with leucovorin ($20\;mg/m^2/day$), every 4 weeks interval for 6 cycles. Oral Uracil/Tegafur on a daily basis for $6{\sim}12$ months was given in 6 patients. Radiotherapy with 45 Gy was delivered to the surgical bed and regional pelvic lymph node area, followed by $5.4{\sim}9\;Gy$ boost to the surgical bed. The follow up period ranged from 8 to 75 months with a median 35 months. $\underline{Results}$: Treatment failure occurred in 17 patients (37%). Locoregional failure occurred in 4 patients (8.7%) and distant failure in 16 patients (34.8%). There was no local failure only. Five year actuarial overall survival (OS) was 51.5% and relapse free survival (RFS) was 58.7%. The OS and RFS were 100%, 100% in stage N0 patients, 53.7%, 47.6% in N1 patients, and 0%, 41.2% in N2 patients (p=0.012, p=0.009). The RFS was 55%, 78.5%, and 31.2% in upper, middle, and lower rectal cancer patients, respectively (p=0.006). Multivariate analysis showed that N stage (p=0.012) was significant prognostic factor for OS and that N stage (p=0.001) and location of tumor (p=0.006) were for RFS. Bowel complications requiring surgery occurred in 3 patients. $\underline{Conclusion}$: Postoperative adjuvant chemoradiotherapy was an effective modality for locoregional control of rectal cancer. But further investigations for reducing the distant failure rate are necessary because distant failure rate is still high.

• Journal of Gastric Cancer
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• v.1 no.4
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• pp.221-227
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• 2001

Purpose: We have carried out prospective randomized clinical trial to compare survival benefit and side effect among three postoperative adjuvant chemotherapeutic regimens in serosa-negative gastric cancer patients. Materials and Methods: Total 317 cases were recognized as serosa negative and randomized into three groups at operating room. Out of them, 172 cases were excluded because of various reasons and 135 cases were analyzed finally; Group A 36 cases, Group B 49 cases, Group C 50 cases. Group A were treated with intravenous FP combination therapy, group B with MF combination therapy and group C with oral $UFT^{(R)}$ (mixture of Tegafur and Uracil) for one year. The median follow-up period was 30 months. Results: $88.9\%$ of Group A, $83.7\%$ of Group B and $90.4\%$ of Group C received adequate chemotherapy. The complication rates of Group A ($44.4\%$) was significantly higher than group B ($20.4\%$) and group C ($24.0\%$)(P<0.05). Most frequent complications were nausea and vomiting. The 3-year survival rates and disease-free survival rates were $92.2\%$ and $89.9\%$ respectively (Group A: $96.6\%,\;87.8\%$, B: $90.3\%,\;87.7\%$, C: $95.7\%,\;93.8\%$). There were no significant differences in survival rate and disease-free survival rate among the three groups (P>0.05). Conclusion: This study might suggest that the survival benefit of postoperative adjuvant chemotherapy for gastric Pseudomonas aeruginosa, and therefore it may be a useful adjunct tool for detection of Pseudomonas aeruginosa infection in combination with other conventional techniques.