Search

Human telomerase reverse transcriptase (hTERT) expression level may not always correlate with telomerase activity. The present study analyzed hTERT splicing patterns with respect to hTERT and telomerase activity in colorectal cancer. Telomerase activity was determined by telomeric repeat amplification protocol assay, and spliced variants of hTERT were identified by reverse transcription-polymerase chain reaction in 40 colorectal cancer tissue samples. In the lower range of telomerase activity (0-100 units), the percentage of the β variant decreased with the increment in telomerase activity, whereas in the higher range of telomerase activity (>100 units), total hTERT expression level revealed a trend toward increment. There was a positive correlation between the full-length variant level and β variant level. Conversely, there was a negative correlation between the percentage of the full-length variant and β variant. Tumor-node-metastasis stage was the strongest prognostic factor in multivariate analysis and the percentage of the full-length variant was an independent prognostic factor for survival. Telomerase activity was primarily altered with changes in alternative splicing of the full-length and β variants of hTERT in colorectal cancer. [ABSTRACT FROM AUTHOR]

The symposium on "Oncology Leadership in Asia" was held as part of the official program of the 42nd Annual Meeting of the Korean Cancer Association with International Cancer Conference. Given the increasing incidence of cancer in all countries and regions of Asia, regardless of developmental stage, and also in light of the recognized need for Asian countries to enhance collaboration in cancer prevention, research, treatment and follow-up, the symposium was held with the aim of bringing together oncology specialists from eight countries and regions in Asia to present the status in their own national context and discuss the key challenges and requirements in order to establish a greater Asian presence in the area of cancer control and research. The task of bringing together diverse countries and regions is made all the more urgent in that while Asia now accounts for more than half of all new cancer cases globally, clinical guidelines are based predominantly on practices adopted in Western countries, which may not be optimized for unique ethnic, pharmacogenomic and cultural characteristics in Asia. Recognizing the need for Asia to better gather information and data for the compilation of Asia-specific clinical guidelines, the participants discussed the current status in Asia in the national and regional contexts and identified future steps towards integrated and collaborative initiatives in Asia. A key outcome of the symposium was a proposal to combine and integrate the activities of existing pan-Asian societies, including the Asian Pacific Federation of Organizations for Cancer Research and Control (APFOCC) and Asian Clinical Oncology Society (ACOS). Further proposals included the expansion of pan-Asian society membership to include individuals and the essential need to encourage the participation of young researchers in order to ensure self-sustainability of cancer control efforts in the future. [ABSTRACT FROM AUTHOR]

Purpose Hypermethylation of the CpG island of p16INK4a occurs in a significant proportion of colorectal cancer (CRC). We aimed to investigate its predictive role in CRC patients treated with 5-fluorouracil, leucovorin, irinotecan (FOLFIRI), and cetuximab. Materials and Methods Pyrosequencing was used to identify KRASmutation and hypermethylation of 6 CpG island loci (p16, p14, MINT1, MINT2, MINT31, and hMLH1) in DNA extracted from formalin-fixed paraffin-embedded specimens. Logistic regression and Cox regression were performed for analysis of the relation between methylation status of CpG island methylator phenotype (CIMP) markers including p16 and clinical outcome. Results Hypermethylation of the p16 gene was detected in 14 of 49 patients (28.6%) and showed significant association with KRASmutation (Fisher exact, p=0.01) and CIMP positivity (Fisher exact, p=0.002). Patients with p16-unmethylated tumors had significantly longer time to progression (TTP; median, 9.0 months vs. 3.5 months; log-rank, p=0.001) and overall survival (median, 44.9 months vs. 16.4 months; log-rank, p=0.008) than those with p16-methylated tumors. Patients with both KRAS and p16 aberrancy (n=6) had markedly shortened TTP (median, 2.8 months) compared to those with either KRAS or p16 aberrancy (n=11; median, 8.6 months; p=0.021) or those with neither (n=32; median, 9.0 months; p < 0.0001). In multivariate analysis, KRAS mutation and p16 methylation showed independent association with shorter TTP (KRAS mutation: hazard ratio [HR], 3.21; p=0.017; p16 methylation: HR, 2.97; p=0.027). Conclusion Hypermethylation of p16 was predictive of clinical outcome in metastatic CRC patients treated with cetuximab and FOLFIRI, irrespective of KRAS mutation. [ABSTRACT FROM AUTHOR]

Purpose Colorectal cancer patients with liver-confined metastases are classified as stage IV, but their prognoses can differ from metastases at other sites. In this study, we suggest a novel method for risk stratification using clinically effective factors. Materials and Methods Data on 566 consecutive patients with colorectal liver metastasis (CLM) between 1989 and 2010 were analyzed. This analysis was based on principal component analysis (PCA). Results The survival rate was affected by carcinoembryonic antigen (CEA) level (p < 0.001; risk ratio, 1.90), distribution of liver metastasis (p=0.014; risk ratio, 1.46), and disease-free interval (DFI; p < 0.001; risk ratio, 1.98). When patients were divided into three groups according to PCA score using significantly affected factors, they showed significantly different survival patterns (p < 0.001). Conclusion The PCA scoring system based on CEA level, distribution of liver metastasis, and DFI may be useful for preoperatively determining prognoses in order to assist in clinical decisionmaking and designing future clinical trials for CLM treatment. [ABSTRACT FROM AUTHOR]

Background We investigated the diagnostic and prognostic usefulness of anaplastic lymphoma kinase (ALK) expression in Asian rhabdomyosarcoma (RMS) patients. Patients and methods A total of 38 RMS tissue samples were collected over a 14-year period (1998- 2012). ALK protein expression and gene copy number were analysed by immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH). Results Ten of the 38 RMS patients (26.3%) showed positive ALK protein expression. ALK protein expression was predominantly positive in alveolar RMS (ARMS) compared with embryonal RMS (ERMS) (80% vs 20%, p=0.03). ALK protein expression was statistically associated with ARMS histology, metastatic disease at diagnosis, and primary trunk site. In FISH analysis, no translocations were detected and ALK gene copy number gain was observed more frequently in ARMS than in ERMS (40% vs 17%). The ALK-positive group showed inferior overall survival (OS) compared with ALK-negative group (p=0.014) for both alveolar and embryonal RMS patients. In multivariate analysis, positive ALK expression was an independent prognostic factor for OS (p=0.02; HR, 3.1; 95% CI 1.2 to 8.3). There was a significant strong positive correlation between ALK gene copy number and protein expression (Spearman's r<0.001, r=0.77). Conclusions We demonstrated that ALK protein expression is statistically associated with ARMS histology, metastatic disease at diagnosis and primary trunk site. Additionally, ALK expression was an independent prognostic factor for worse survival. There was a strong correlation between IHC and FISH. Further studies are needed to evaluate the potential diagnostic and therapeutic role of ALK expression in RMS. [ABSTRACT FROM AUTHOR]

Purpose: The combination of gemcitabine and docetaxel (GD) is used to effectively treat patients with soft tissue sarcoma (STS). It is widely considered that the conventional doses used are too high for long term use and many patients must discontinue GD treatment due to its toxicity. Therefore, to determine the appropriate dose meeting acceptable efficacy results, while minimizing toxic side effects, we treated patients with a weekly infusion of GD (weekly GD). Materials and Methods: A total of 22 patients presenting a variety of STSs were treated at Yonsei Cancer Center. All patients had metastatic or recurrent cancer and had previously received doxorubicin and ifosfamide combination chemotherapy. In all cases, gemcitabine (1,000 mg/m2) and docetaxel (35 mg/m2) were administered intravenously on days 1 and 8 of a 21-day cycle. We retrospectively reviewed the medical records of these patients. Results: The response rate was 4.5%, with one patient diagnosed with leiomyosarcoma having a partial response, and the disease control rate was 40.9%. The median progression-free survival (PFS) duration was 2.7 months and the PFS was correlated with the treatment response to a weekly GD. The median overall survival (OS) duration was 7.8 months and the OS was correlated with histology. There was no significant difference in OS between patients who received weekly GD as a 2nd line chemotherapy and those who received 3rd line or more. Treatment was generally well tolerated. Conclusion Weekly GD was well tolerated and showed moderate efficacy, indicating that this could be a reasonable option as a salvage treatment for metastatic STS. [ABSTRACT FROM AUTHOR]

The article compares two weekly docetaxel-based regimens as first-line treatments for advanced gastric cancer and investigates the expression of secreted protein acidic and rich in cysteine (SPARC) and its abilities to protect treatment-related clinical outcomes. The results indicate that split-dose weekly docetaxel alleviates hematological toxicity. Researchers also conclude that SPARC expression may help individualize therapy in advanced gastric cancer.

We analyzed the natural history of advanced gastric cancer with sequential salvage chemotherapy following first-line treatment. We studied 532 patients with unresectable gastric adenocarcinoma who were treated at Yonsei Cancer Center (2000–2008). The patients were managed with multiple sequential salvage chemotherapy as allowed by performance status and toxicity profiles. The tumor response was assessed every two cycles. Four hundred sixty patients received palliative chemotherapy and 72 received supportive care only. The median overall survival was 12.0 months for all patients, 12.1 months for the chemotherapy group, and 2.5 months for the supportive care group ( P < 0.001). In the chemotherapy group, 87% received first-line chemotherapy, 47% second-line, 23% third-line, 9% fourth-line, and 3% fifth-line. Response rates were 24.8, 12.6, 10.9, 2.6, and 0% and disease control rates were 76.3, 60.1, 54.2, 54.2, and 53.3% for first- to fifth-line treatment, respectively. The median progression-free survival was 5.5, 3.4, 2.5, 1.9, and 2.0 months and overall survival was 12.1, 7.9, 5.5, 5.0, and 6.8 months. Performance status and metastatic pattern were consistent prognostic factors throughout salvage treatment. Clinical trials may be feasible in second- or third-line salvage chemotherapy for gastric cancer. Future clinical trials in these settings should take into account the low response rate, short progression-free survival, and the prognostic factors for optimal trial design. [ABSTRACT FROM AUTHOR]

We evaluated the efficacy and tolerability of combined paclitaxel and ifosfamide in anthracycline- and docetaxel-pretreated metastatic breast cancer (MBC). Patients received paclitaxel (175 mg/m2 i.v. in a 3-h infusion) on day 1 and ifosfamide (1.5 g/m2 i.v. in a 15-min infusion) on days 1–3, every 3 weeks for a maximum of nine cycles. The tumor response was assessed every two cycles. We enrolled 34 patients with a median age of 50 years. Thirty patients had visceral metastases. Anthracycline- and docetaxel-based chemotherapy had previously been administered to 18/13 and 13/21 patients, respectively, in (neo)adjuvant/metastatic settings. Three patients had not previously received anthracycline due to abnormal cardiac functions. A total of 174 cycles of chemotherapy were delivered with a median of six cycles. The response rate under the intent-to-treat analysis was 23.5% (all partial responses) with a median response duration of 14 months. The disease control rate was 70.6%. The median progression-free and overall survival were 5.9 and 8.5 months, respectively. There was no apparent relationship between activity and prior docetaxel resistance. The incidence of grade III/IV neutropenia was 46.6% (81 of 174 cycles) with febrile neutropenia of only 1.7%. Major grade III/IV non-hematological toxicities included peripheral neuropathy (6 of 34 patients) and infection (4 of 34 patients). There were no treatment-related deaths. Paclitaxel combined with ifosfamide was effective and tolerable in anthracycline-/docetaxel-pretreated MBC. Overcoming docetaxel resistance by using paclitaxel in combination with ifosfamide needs to be addressed through further investigation. [ABSTRACT FROM AUTHOR]

Small bowel adenocarcinoma (SBA) is a rare malignancy with a poor outcome. We evaluated the natural history of SBA at a single Korean institute. Medical records of 100 patients with SBA were reviewed for clinical characteristics, treatment patterns, outcomes, and prognostic factors. The most common primary tumor site was the duodenum (82%). Seventy-four patients were diagnosed with stage III/IV disease (28/46 patients, respectively). Sixty-six patients had surgery (R0/R1/R2 in 32/2/32) without operation-related mortality. Of 34 R0/R1-resected patients, 16 received adjuvant chemotherapy. The dominant pattern of recurrence following R0/R1 resection was distant metastasis (29%; 10 of 34 patients). Thirty-four patients with advanced SBA received palliative chemotherapy, showing a response rate of 27.6% and a median progression-free survival of 3.8 months. The median overall survival for all patients and R0/R1-resected patients was 10.5 and 42.1 months, respectively. In multivariate analysis, lower stage, nonduodenal location, and R0/R1 resection were good independent prognostic factors. Early diagnosis is crucial to improve outcomes of SBA with respect to increasing resectability. Distant metastasis as a dominant pattern of recurrence suggests a potential role for adjuvant chemotherapy. Newer antitumor agents in advanced SBA should be evaluated considering the poor efficacy of current palliative chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the efficacy and safety of weekly paclitaxel monotherapy in previously treated patients with advanced gastric cancer (AGC) and poor performance status (PS) according to the Eastern Cooperative Oncology Group (ECOG). Patients and Methods: Patients with evaluable disease who failed at least one previous chemotherapy and had a PS of 2–3, received paclitaxel 70 mg/m2 on days 1, 8 and 15 every 4 weeks. Results: The median overall survival (OS) was 5.5 months (95% confidence interval, CI, 3.3–7.8) and progression-free survival was 2.1 months (95% CI, 1.2–3.0). The overall response rate was 3.8% and the disease control rate was 25.0%. Treatment-related toxicities were tolerable. OS was 7.1 (95% CI, 5.4–9.5) and 3.7 months (95% CI, 2.1–5.3) for patients with PS-ECOG 2 and 3, respectively (p < 0.001). When evaluated according to the previous treatment, OS was 5.1 (95% CI, 3.3–7.0) and 6.5 months (95% CI, 3.8–9.3) for patients receiving two and three or more lines of treatment, respectively (p = 0.815). With multivariate analysis, PS was a significant factor for OS. Conclusion: Survival in patients treated with weekly paclitaxel monotherapy was comparable to other second- or third-line chemotherapies for AGC, with acceptable toxicities in previously treated patients with poor PS. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: This prospective, multicenter, phase 2 study evaluated the efficacy and safety of imatinib mesylate and assessed KIT and PDGFRA gene mutation status in Korean patients with gastrointestinal stromal tumors (GISTs). Methods: Forty-seven patients with pathologically proven KIT-positive metastatic or unresectable GISTs were accrued from eight institutions in Korea. Imatinib was administered orally at 400 mg once daily. In case of disease progression, the dose was escalated to 600 mg once daily, then 400 mg twice daily. KIT and PDGFRA mutations were analyzed in 29 of the 47 patients. Results: Imatinib produced partial responses in 30 patients (63.8%; 95% confidence interval, 50.1–77.6%) and stable disease in 13 patients (27.7%). The median time to response was 2.6 months (range, 1.0–6.2 months). With a median follow-up of 62 months (range, 32–67 months), 4-year progression-free survival and overall survival rates were 50 and 65%, respectively. The most common adverse events were anemia, neutropenia, edema, and skin rash (predominantly of grade 1–2). There were no treatment-related deaths. In the subset evaluated for mutational status, 24 patients (82.8%) had KIT exon 11 mutations and 1 (3.4%) had a KIT exon 9 mutation. Conclusions: Imatinib is effective and safe in Korean patients with metastatic or unresectable GIST. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The aim of this study was to scrutinize the evidence of adjuvant chemotherapy of gastric cancer by assessing the quality of the medical literature of randomized controlled trials (RCTs). A quality assessment (QA) scoring system was devised with the three parameters—control of bias, quality of report, and quality of design—which consisted 19 items. We searched for all the publications of the RCTs, from 1969 to 2007, with surgery-only arm, and their associated meta-analyses to score. Among the 26 RCTs, quality of three articles were graded as (2+), 10 articles as (1+), and 13 articles as (−). Recently published studies had overall better quality of report, but not necessarily better quality of design. Three studies demonstrating a positive survival benefit of adjuvant chemotherapy had a grade (1+). Hierarchical clustering revealed that the 26 articles were grouped into three major branches associated with study quality and a multi-institutional setting. We also obtained a statistically significant set of ten items ( P < 0.001) that could differentiate articles of good (1–2+) and low quality (−) through supervised two-way hierarchical clustering. Finally, the level of recommendation for adjuvant chemotherapy in gastric cancer was to be a “B” according to the Scottish Intercollegiate Guidelines Network (SIGN) System. QA of medical literature should be an essential consideration for medical-related decision-making and the formation of evidence-based guidelines. Multidisciplinary discussion to develop and refine trial design is important for procuring better quality of RCTs of adjuvant chemotherapy of gastric cancer. [ABSTRACT FROM AUTHOR]

The purpose of this study is to investigate prognostic factors affecting oncologic outcomes in patients with locally recurrent rectal cancer and determine whether recurrence patterns influence curative resection of recurrent tumor. We examined 62 patients with isolated local recurrence following total mesorectal excision (TME) of the primary rectal cancer. Recurrence patterns were classified as central, anterior, posterior, lateral, and perineal with respect to the intra-pelvic tumor location. Prognostic factors affecting oncologic outcomes were analyzed, and the rate of curative resection was analyzed according to recurrence patterns. The mean follow-up period was 49.0 ± 29.0 months, and the mean time to recurrence after TME was 27.9 ± 23.3 months. Twenty-three patients underwent curative resection, and the remaining 39 patients received palliative treatment. Patients with a central recurrence had the highest rate of curative resection ( p = 0.006). The overall 5-year survival rate was 13.9% and significantly higher in those treated with curative resection (35.1%; p = 0.0002). Multivariate analysis demonstrated that disease-free survival less than 1 year and curative resection of local recurrence were independent prognostic factors influencing 5-year survival. Patients with central recurrences have a high probability of curative resection. Disease-free survival less than 1 year and curative resection of local recurrence were independent prognostic factors affecting oncologic outcomes in patients with locally recurrent rectal cancer. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the efficacy and safety of the combination chemotherapy of paclitaxel, infusional 5-fluorouracil (5-FU) and leucovorin (FLT regimen) in advanced gastric cancer. The primary end point was the time to progression (TTP). Patients with evaluable disease with or without measurable lesions received 175 mg/m2 paclitaxel on day 1 followed by 20 mg/m2 leucovorin and 24-h infusion of 5-FU 1,000 mg/m2 (day 1-3) repeated every 3 weeks. Sixty patients were enrolled. The median TTP and overall survival duration were 13 and 60 weeks, respectively. One-year survival rate was 53.3%. Of the 50 patients with measurable lesion, the overall response rate was 31.7%. The most common grade 3–4 adverse event was neutropenia (61.7%). The FLT regimen showed an efficacy comparable to other regimens of cisplatin or anthracycline combinations with the advantage of remarkably low non-hematological toxicity. These data about the efficacy of this regimen need confirmation in a phase III trial. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the activity and the safety of a combination regimen of capecitabine and doxorubicin as salvage chemotherapy in advanced gastric cancer patients who had undergone one or two prior chemotherapy regimens. Patients received capecitabine, 2,500 mg/m2/day PO for 14 days (D1–14) and doxorubicin, 30 mg/m2 IV on day 1 every 3 weeks until disease progression. The response was evaluated according to RECIST criteria, and the toxicity was evaluated by NCI-CTC (version 2.0). Forty-five patients were enrolled. Twenty-six patients were treated as second-line chemotherapy and the remaining patients as third-line chemotherapy. A total of 152 cycles of chemotherapy (median 2, range 1–12) were administered. Median dose intensities of capecitabine and doxorubicin were 11,326 and 9.6 mg/m2/week, respectively. The overall response rate was 6.7% (95% CI, 4.1–12.5%) and the disease control rate was 46.7% (95% CI, 28.6–87.1%) according to an intent-to-treat analysis. The median progression-free survival was 11.3 weeks (95% CI, 5.6–16.7 weeks). The median overall survival was 29.1 weeks (95% CI, 18.3–39.9 weeks) with one-year survival rate of 24%. Severe (grade III/IV) hematologic and non-hematologic toxicity was uncommon and included nausea/vomiting in five (11.1%), neutropenia in two (4.4%), anemia in one (2.2%), and hand-foot syndrome in one patient (2.2%). The combination of capecitabine and doxorubicin is a feasible salvage regimen in advanced pre-treated gastric cancer. [ABSTRACT FROM AUTHOR]

Since the combination of capecitabine and irinotecan has successfully been used as a first-line treatment in metastatic colorectal cancer (MCRC), we expected promising results when given as a second-line treatment to metastatic colorectal patients who had been pretreated with 5-Fluorouracil and Oxaliplatin. Thirty-three MCRC patients participated in this study and received an oral dose of 1,000 mg/m2 capecitabine twice daily on days 1–14 and a dose of 100 mg/m2 irinotecan infused over 90 min on days 1 and 8, every 3 weeks. The overall response rate in intent-to-treat was 33.3% (95% CI, 21.5–58.3%), including one complete response (3.0%) and ten partial responses (30.3%); 12 patients (36.4%) had disease stabilization and only 9 (27.3%) progressed. The median time to progression was 6.7 months (95% CI, 4.8–8.6 months). After a median follow-up time of 12 months, nine patients (27.3%) were still alive with metastatic disease. The median response duration for all patients was 6.7 months (95% CI, 3.9–9.5 months) and the median overall survival was 13.4 months (95% CI, 11.0–15.8 months) with a 1-year survival rate of 55.4%. Myelosuppression was commonly observed; NCI-CTC (v 2.0) grade 3/4 neutropenia, however, occurred in eight (24%) patients and grade 3 anemia was seen in one patient (3%). The most common (grade 3/4) non-hematological toxicity was diarrhea (15%) and the other severe grade 3/4 toxicities included nausea/vomiting in one patient (3%), stomatitis in one patient (3%), hand-foot syndrome in one patient (3%). The combination of capecitabine and irinotecan is an effective and well-tolerated regimen for second-line treatment of metastatic colorectal cancer. However, further phase III trials are required to clarify its use in the treatment of metastastic colorectal cancer patients who have been pretreated with 5-fluorouracil and oxaliplatin. [ABSTRACT FROM AUTHOR]

Background: The objectives of this study were to evaluate long-term results of concurrent chemoradiotherapy (CRT) with 5-fluorouracil and cisplatin and the potential benefit of consolidation chemotherapy in patients with anal squamous cell carcinoma (ASCC). Methods: Between January 1995 and February 2006, 31 patients with ASCC were treated with CRT. Radiotherapy was administered at 45 Gy over 5 weeks, followed by a boost of 9 Gy to complete or partial responders. Chemotherapy consisted of 5-fluorouracil (750 or 1,000 mg/m²) daily on days 1 to 5 and days 29 to 33; and, cisplatin (75 or 100 mg/m²) on day 2 and day 30. Twelve patients had T3-4 disease, whereas 18 patients presented with lymphadenopathy. Twenty-one (67.7%) received consolidation chemotherapy with the same doses of 5-fluorouracil and cisplatin, repeated every 4 weeks for maximum 4 cycles. Results: Nineteen patients (90.5%) completed all four courses of consolidation chemotherapy. After CRT, 28 patients showed complete responses, while 3 showed partial responses. After a median follow-up period of 72 months, the 5-year overall, disease-free, and colostomy-free survival rates were 84.7%, 82.9% and 96.6%, demonstrating that CRT with 5-fluorouracil and cisplatin yields a good outcome in terms of survival and sphincter preservation. No differences in 5-year OS and DFS rates between patients treated with CRT alone and CRT with consolidation chemotherapy was observed. Conclusion: our study shows that CRT with 5-FU and cisplatin, with or without consolidation chemotherapy, was well tolerated and proved highly encouraging in terms of long-term survival and the preservation of anal function in ASCC. Further trials with a larger patient population are warranted in order to evaluate the potential role of consolidation chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose. We examined the pattern of single-nucleotide polymorphisms (SNPs) of gemcitabine metabolism-related and target genes in breast cancer patients and evaluated their association with drug response or toxicity. Patients and Methods. SNPs in deoxycytidine kinase (dCK), deoxycytidine monophosphate deaminase (DCTD), and ribonucleotide reductase M1 polypeptide (RRM1) were analyzed with genomic DNA of 10 breast cancer cell lines, 74 peripheral blood mononuclear cell (PBMC) samples from advanced breast cancer patients treated with gemcitabine, and 56 PBMC samples from healthy volunteers. Results. The incidences of SNPs of breast cancer patients were 1.4% in dCK (626 A>G), 10.8% in DCTD (315 T>C), 40.5% in the first RRM1 (1082 C>A), 44.6% in the second RRM1 (2455 A>G), 44.6% in the third RRM1 (2464 G>A), and 23% in two RRM1 sites (2455A>Gand 2464G>A) that were similar to those of the normal control group. We found a double SNP of RRM1 (2455 A>G and 2464 G>A) to be the novel haplotype that was associated with a lower frequency of chemotherapy-induced toxicity, such as neutropenia (p < .01) and G-CSF requirement (p < .005). Conclusion. RRM1 haplotype showed an association with susceptibility to gemcitabine monotherapy in breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: The standard chemotherapy regimen for advanced gastric cancer has not yet been established. We investigated the efficacy and the safety of the combination of docetaxel with infusional 5-fluorouracil (5-FU) and leucovorin (FLT) in advanced gastric cancer. Methods: Patients received docetaxel 75 mg/m2 (1-hour infusion) followed by a leucovorin bolus 20 mg/m2 and a 24-hour infusion of 5-FU 1,000 mg/m2 (day 1–3) every 3 weeks. The response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and the toxicity was evaluated by National Cancer Institute common toxicity criteria (NCI-CTC). Results: Sixty-six patients were enrolled. Median relative dose intensity was 86%. Of 57 evaluable patients, the overall response rate was 25.7%. The response rate was 34.2% in chemonaïve patients and 14.2% in the patients who had previously received treatment. Median time to progression and overall survival duration were 5.2 and 9.7 months, respectively. The most frequent grade 3–4 toxicity was neutropenia, which was the major cause of treatment delay. Other hematological and nonhematological toxicities were rare. Conclusions: The FLT regimen showed a comparable efficacy with other second-generation regimens. Because of the low nonhematological toxicity, this could be a potential alternative to the cisplatin-containing regimens in gastric cancer. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Thirty patients with nasal natural killer (NK)/T-cell lymphoma, who underwent systemic chemotherapy with or without involved-field radiotherapy between 1993 and 1998, were retrospectively reviewed to determine the clinical significance of P-glycoprotein immunohistochemically identified in tumor specimens. Eighty percent of previously untreated patients expressed P-glycoprotein. According to P-glycoprotein immunoreactivity, all patients with nasal NK/T-cell lymphoma were divided into 2 groups; (a) P-glycoprotein-negative group ( N  = 6) and (b) P-glycoprotein-positive group ( N  = 24). There was no significant difference in clinical profiles between both groups. Regardless of the P-glycoprotein expressions, Epstein-Barr virus genomes were almost identically detected in patients of the 2 groups. Contrary to our expectations, however, P-glycoprotein expressions were not found to be a strong predictor of chemotherapy resistance. Although 2 (33%) of 6 P-glycoprotein-negative patients and 10 (42%) of the 24 P-glycoprotein-positive patients showed a favorable response to systemic chemotherapy, 4 (67%) of 6 P-glycoprotein-negative patients did not achieve complete response (CR) to chemotherapy, which led to an early death, whereas 4 (17%) of the 24 P-glycoprotein-positive patients achieved CR to chemotherapy despite positive P-glycoprotein immunoreactivity. Overall, there were no significant differences in either CR rate or the response rate of patients in the two groups. Overall 5-year actuarial survival and disease-free survival for all patients were 44% and 47%, respectively, but no differences in survival rates were observed between 2 groups. (5-year actuarial survival rate: 33% for the P-glycoprotein-negative, 50% for the P-glycoprotein-positive) ( P  = 0.7093, log-rank). On univariate and multivariate analyses, P-glycoprotein expressions by immunohistochemical study were not found to be an important prognostic factor. Given these observations, we conclude that the molecular mechanisms of resistance to chemotherapy in nasal NK/T-cell lymphoma patients are not entirely dependent on P-glycoprotein, and that other complex mechanisms of drug action and resistance may be likely to be involved. [ABSTRACT FROM AUTHOR]

Evaluates intravenous 5-fluorouracil against oral doxifluoridine as preoperative concurrent chemoradiation for locally advanced rectal cancer, with respect to tumor response, toxicity and quality of life of patients. Treatment efficacy.

Discusses whether adding neoadjuvant chemotherapy (CT) to conventional radiation therapy (RT) makes an effective contribution to laryngeal preservation in patients with locally advanced laryngeal cancer. Study of two groups of patients at the Severance Hospital in Seoul, South Korea; Five-year survival rate of patients; Investigation of differences in organ preservation rate and treatment results.

A letter to the editor is presented about the effectiveness of cetuximab in preventing rapid progression of non-small cell lung cancer.

The article reports on the results of research which was conducted in an effort to compare chemotherapy plus cetuximab with chemotherapy alone in patients with advanced EGFR-positive non-small-cell lung cancer. Researchers used a multinational, multicentre, open-label, phase III trial to evaluate cancer patients. They found that the patients who were given chemotherapy plus cetuximab survived longer than those in the chemotherapy-alone group, and that the addition of cetuximab to platinum-based chemotherapy represents a new treatment option for patients with advanced non-small-cell lung cancer.