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Y-K Kang, H-M Chang,
J H Yook,
M-H Ryu,
I Park,
Y J Min,
D Y Zang,
G Y Kim,
D H Yang,
S J Jang,
Y S Park,
J-L Lee,
T W Kim,
S T Oh,
B K Park,
H-Y Jung,
B S Kim
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ABSTRACT: Background:This phase 3 study evaluated the efficacy of new adjuvant chemotherapy (MFP), which intensified the mitomycin-C (MMC) plus short-term doxifluridine (Mf) for gastric cancer.Patients and methods:A total of 855 patients (424 in Mf, 431 in MFP) with pathological stage II-IV (M0) gastric cancer after D2 gastrectomy were randomly assigned to receive either Mf (MMC 20 mg m-2, followed by oral doxifluridine 460-600 mg m-2 per day for 3 months) or MFP (MMC 20 mg m-2, followed by oral doxifluridine 460-600 mg m-2 per day for 12 months with 6 monthly infusions of 60 mg m-2 of cisplatin) chemotherapy.Results:With a median follow-up of 6.6 years, there was no difference between the two groups in recurrence-free survival (RFS) (5-year RFS 61.1% in Mf and 57.9% in MFP; hazard ratio 1.10 (95% CI 0.89-1.35); P=0.39) and overall survival (OS) (5-year OS 66.5% in Mf and 65.0% in MFP; hazard ratio 1.11 (95% CI 0.89-1.39); P=0.33).Conclusion:Intensification of Mf adjuvant chemotherapy by prolonging the duration of oral fluoropyrimidine and adding cisplatin was safe but not effective to improve the survivals in curatively resected gastric cancer patients.British Journal of Cancer advance online publication 28 February 2013; doi:10.1038/bjc.2013.86 www.bjcancer.com.
British Journal of Cancer 02/2013; · 5.04 Impact Factor
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ABSTRACT: To assess the efficacy and safety of individualised dose optimisation of irinotecan monotherapy as salvage treatment for advanced gastric cancer (AGC).
A total of 43 patients were enrolled. Intravenous irinotecan (350 mg m(-2)) was administered every 3 weeks. The dose was increased (425 mg m(-2) and 500 mg m(-2)) or decreased (250 mg m(-2)) depending on patient tolerance. UGT1A1 genotypes were determined by direct sequencing of genomic DNA extracted from peripheral blood.
A total of 183 cycles of irinotecan were administered, with a median of four cycles per patient. The overall response rate was 9.3%, and the disease control rate was 62.8%. Median time to disease progression was 2.8 months, and median overall survival was 8.0 months. Grade 3-4 neutropenia was the most common toxicity (53.5%), and febrile neutropenia was the least common toxicity (4.6%). Compared with defective allele groups, UGT1A1 *1/*1 was associated with a lower incidence of grade 3-4 neutropenia during the first cycle (P=0.018).
Individualised irinotecan dose escalation based on patient tolerance was not associated with increased toxicity and shows modest activity as salvage chemotherapy for AGC. The role of UGT1A1 genotype in clinical toxicity requires further evaluation.
British Journal of Cancer 04/2012; 106(10):1591-7. · 5.04 Impact Factor
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ABSTRACT: To evaluate the activity and safety of everolimus and identify potential biomarkers for efficacy of everolimus in patients with advanced gastric cancer (AGC), who failed both fluoropyrimidine and platinum.
Fifty-four patients received everolimus (10 mg day(-1)). The primary objective was to determine the 4-month progression-free survival (PFS) rate, assumed to be 30%. We additionally investigated the potential biomarkers for everolimus as an exploratory endpoint in those who underwent tumour biopsies.
Two patients (3.7%) achieved partial response and the disease control rate (DCR) was 38.9%. At a median follow-up duration of 8.7 months, the 4-month PFS rate was 18.4%, not fulfilling the primary hypothesis, with a median PFS of 1.7 months and a median overall survival of 8.3 months. The high expression of pS6(Ser240/4) at baseline was significantly associated with higher DCR (P=0.043) and prolonged PFS (P=0.001). Grade 1/2 asthenia (96.3%) recorded as the leading toxicity and hyperglycaemia (20.4%) was the most common non-hematological grade 3/4 toxicity. Three patients experienced grade 3/4 pneumonitis. Notably, two experienced treatment-related deaths.
Everolimus is active against a limited number of patients with AGC. pS6(Ser240/4) may be a potential predictive biomarker for everolimus, which requires validation. Careful monitoring is necessary despite generally favourable toxicity profile.
British Journal of Cancer 02/2012; 106(6):1039-44. · 5.04 Impact Factor
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K-p Kim,
G Jang,
Y S Hong,
H-S Lim,
K-s Bae,
H-S Kim,
S S Lee,
J-G Shin,
J-L Lee,
M-H Ryu, H-M Chang,
Y-K Kang,
T W Kim
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ABSTRACT: Advanced biliary cancer is often treated with fluoropyrimidine-based chemotherapy. In this study, we evaluated the efficacy and tolerability of a combination of S-1, an oral fluoropyrimidine prodrug, and oxaliplatin in patients with metastatic biliary cancer.
Patients with histologically confirmed metastatic biliary cancer and no history of radiotherapy or chemotherapy were enrolled. Oxaliplatin was administered intravenously (130 mg m(-2)), followed by 14-day administration of oral S-1 (40 mg m(-2) twice daily) with a subsequent 7-day rest period every 21 days. Pharmacokinetic analysis of S-1 was performed at cycle 1. Patients were genotyped for CYP2A6 polymorphisms ((*)1, (*)4, (*)7, (*)9 or (*)10), and pharmacokinetic and clinical parameters compared according to the CYP2A6 genotype.
In total, 49 patients were evaluated, who received a median of four cycles. The overall response rate was 24.5%. Median progression-free and overall survival was 3.7 and 8.7 months, respectively. The most common haematological grade 3 out of 4 toxicity was neutropenia (14%), while non-hematological grade 3 out of 4 toxicities included anorexia (14%), nausea (12%), asthenia (10%), vomiting (10%), and diarrhoea (4%). Biotransformation of S-1 (AUC(0-24 h) of 5-fluorouracil/AUC(0-24 h) of tegafur) was 1.85-fold higher for the *1/*1 group than for the other groups (90% confidence interval 1.37-2.49). Diarrhoea (P=0.0740), neutropenia (P=0.396), and clinical efficacy (response rate, P=0.583; PFS, P=0.916) were not significantly associated with CYP2A6 genotype, despite differences in 5-FU exposure.
The combination of S-1 and oxaliplatin appears to be active and well tolerated in patients with metastatic biliary cancer, and thus is feasible as a therapeutic modality. CYP2A6 genotypes are associated with differences in the biotransformation of S-1. However, the impact of the CYP2A6 polymorphism on variations in clinical efficacy or toxicity requires further evaluation.
British Journal of Cancer 02/2011; 104(4):605-12. · 5.04 Impact Factor
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ABSTRACT: Background Epidermal growth factor receptor (EGFR) critically regulates tumour cell division, survival and metastasis. Agents that inhibit EGFR have been used in the treatment of advanced-stage malignancies, but cause variable cutaneous side-effects, most often papulopustular eruptions and xerosis.Objectives We assayed expression of inflammatory cytokines [interleukin (IL)-1α, tumour necrosis factor (TNF)-α, interferon (IFN)-γ, human leucocyte antigen (HLA)-DR and intercellular adhesion molecule (ICAM)-1], differentiation markers (filaggrin, involucrin and loricrin) and phosphorylated EGFRs (pEGFRs) in papulopustular eruptions to determine the association between these markers and the eruptions caused by cetuximab.Patients/methods Twelve papulopustular lesion biopsies were selected from patients with colon cancer who had received cetuximab treatment. Immunohistochemistry and immunofluorescence with a confocal laser scanning microscopy were performed.Results Filaggrin expression decreased and expression of involucrin, various inflammatory markers (IL-1α, TNF-α, ICAM-1 and HLA-DR) increased and the expression of pEGFR was markedly downregulated in papulopustular eruptions. In perilesions, decreased pEGFR expression was noted in hair follicles compared with interfollicular epidermis. The increase of IL-1α and TNF-α was observed in perilesions as in the lesions.Conclusions The early inflammatory events (IL-1α and TNF-α expression) seen, and the lack of pEGFR in perilesional follicles, indicate that inflammatory events induced by EGFR inhibition may initiate papulopustular eruptions along with the altered differentiations. The decrease of filaggrin may contribute to the pathogenesis of the xerosis caused by cetuximab.
British Journal of Dermatology 11/2009; 162(2):371 - 379. · 3.67 Impact Factor
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ABSTRACT: Epidermal growth factor receptor (EGFR) critically regulates tumour cell division, survival and metastasis. Agents that inhibit EGFR have been used in the treatment of advanced-stage malignancies, but cause variable cutaneous side-effects, most often papulopustular eruptions and xerosis.
We assayed expression of inflammatory cytokines [interleukin (IL)-1alpha, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, human leucocyte antigen (HLA)-DR and intercellular adhesion molecule (ICAM)-1], differentiation markers (filaggrin, involucrin and loricrin) and phosphorylated EGFRs (pEGFRs) in papulopustular eruptions to determine the association between these markers and the eruptions caused by cetuximab.
Twelve papulopustular lesion biopsies were selected from patients with colon cancer who had received cetuximab treatment. Immunohistochemistry and immunofluorescence with a confocal laser scanning microscopy were performed.
Filaggrin expression decreased and expression of involucrin, various inflammatory markers (IL-1alpha, TNF-alpha, ICAM-1 and HLA-DR) increased and the expression of pEGFR was markedly downregulated in papulopustular eruptions. In perilesions, decreased pEGFR expression was noted in hair follicles compared with interfollicular epidermis. The increase of IL-1alpha and TNF-alpha was observed in perilesions as in the lesions.
The early inflammatory events (IL-1alpha and TNF-alpha expression) seen, and the lack of pEGFR in perilesional follicles, indicate that inflammatory events induced by EGFR inhibition may initiate papulopustular eruptions along with the altered differentiations. The decrease of filaggrin may contribute to the pathogenesis of the xerosis caused by cetuximab.
British Journal of Dermatology 11/2009; 162(2):371-9. · 3.67 Impact Factor
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J-L Lee,
Y-K Kang,
H J Kang,
K-H Lee,
D Y Zang,
B-Y Ryoo,
J G Kim,
S R Park,
W K Kang,
D B Shin,
M-H Ryu, H M Chang,
T-W Kim,
J H Baek,
Y J Min
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ABSTRACT: This randomised multicentre phase II study was conducted to investigate the activity and safety of two oral fluoropyrimidines, capecitabine or S-1, in elderly patients with advanced gastric cancer (AGC). Elderly (>or=65 years) chemo-naive patients with AGC were randomly assigned to receive capecitabine 1250 mg m(-2) two times daily on days 1-14 every 3 weeks or S-1 40-60 mg two times daily according to body surface area on days 1-28 every 6 weeks. Ninety-six patients were enrolled and 91 patients were randomised to capecitabine (N=46) or S-1 (N=45). Overall response rate, the primary end point, was 27.2% (95% CI, 14.1-40.4, 12 of 44 assessable patients) with capecitabine and 28.9% (95% CI, 15.6-42.1, 13 of 45) with S-1. Median times to progression and overall survival in the capecitabine arm (4.7 and 9.5 months, respectively) were similar to those in the S-1 arm (4.2 and 8.2 months, respectively). The incidence of grade 3-4 granulocytopenia was 6.8% with capecitabine and 4.8% with S-1. Grade 3-4 nonhaematologic toxicities were: asthenia (9.1% with capecitabine vs 7.1% with S-1), anorexia (6.8 vs 9.5%), diarrhoea (2.3 vs 0%), and hand-foot syndrome (6.8 vs 0%). Both capecitabine and S-1 monotherapies were active and tolerable as first-line treatment for elderly patients with AGC.
British Journal of Cancer 09/2008; 99(4):584-90. · 5.04 Impact Factor
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ABSTRACT: Paclitaxel and capecitabine, which have distinct mechanisms of action and toxicity profiles, have each shown high activity as single agents in gastric cancer. Synergistic interaction between these two drugs was suggested by taxane-induced upregulation of thymidine phosphorylase. We, therefore, evaluated the antitumour activity and toxicities of paclitaxel and capecitabine as first-line therapy in patients with advanced gastric cancer (AGC). Patients with histologically confirmed unresectable or metastatic AGC were treated with capecitabine 825 mg m(-2) p.o. twice daily on days 1-14 and paclitaxel 175 mg m(-2) i.v. on day 1 every 3 weeks until disease progression or unacceptable toxicities. Between June 2002 and May 2004, 45 patients, of median age 57 years (range=38-73 years), were treated with the combination of capecitabine and paclitaxel. After a median 6 cycles (range=1-9 cycles) of chemotherapy, 43 were evaluable for toxicity and response. A total of 2 patients showed complete response and 20 showed partial response making the overall response rate 48.9% (95% CI=30.3-63.5%). After a median follow-up of 42.2 months (range=31.2-54.3 months), median time to progression was 5.6 months (95% CI=3.9-7.2 months) and median overall survival was 11.3 months (95% CI=8.1-14.4 months). Grade 3 or 4 adverse events include neutropaenia (46.5% of patients), hand-foot syndrome (9.3%), arthralgia (9.3%), and asthenia (4.7%). There was no neutropaenic fever or treatment-related deaths. Paclitaxel and capecitabine combination chemotherapy was active and highly tolerable as a first-line therapy for AGC.
British Journal of Cancer 02/2008; 98(2):316-22. · 5.04 Impact Factor
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ABSTRACT: ZnO epitaxial layers were successfully grown on nitridated Si(1 0 0) substrate with high-temperature (HT) GaN and low-temperature ZnO double buffer layers by molecular beam epitaxy. It was found that the HT-GaN buffer was crystalline with both hexagonal and cubic phases. It was also found that numerous cone-shaped nano-islands were formed on the ZnO epitaxial layers with density, average diameter and average height of 1.25 Â 10 9 cm À2 , 300 nm and 150 nm, respectively. X-ray diffraction and photoluminescence results both indicate that quality of our ZnO epitaxial layers was good.
Journal of Crystal Growth05.Dz. 01/2008; 31015(81).
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ABSTRACT: This study aimed to evaluate the efficacy and safety of 5-fluorouracil (5-FU), doxorubicin and mitomycin-C (FAM) adjuvant chemotherapy in patients who had undergone curative resection of gastric carcinoma.
From Nov 1999 to Jan 2002, 291 consecutive patients with stage IB-IIIB gastric adenocarcinoma were given FAM adjuvant chemotherapy. Chemotherapy comprised intravenous 5-FU 600 mg/m(2) (days 1, 8, 29 and 36), doxorubicin 30 mg/m(2) (days 1 and 29) and mitomycin-C 10 mg/m(2) (day 1), every 8 weeks for 6 months.
The median follow-up time was 60.6 months, 92 patients died, and 93 patients had recurrent disease. The 5-year overall survival (OS) rates were 85.9% for stage IB, 72.1% for stage II, 58.0% for stage IIIA, and 48.2% for stage IIIB (p=0.002). The 5-year relapse-free survival (RFS) rates were 85.2% for stage IB, 71.2% for stage II, 53.3% for stage IIIA, and 39.2% for stage IIIB (p<0.001). A total of 769 cycles of chemotherapy were delivered, and 15 patients experienced grade 3 or higher leukopenia. The most common grade 3 or higher non-hematologic toxicity was nausea/vomiting (11 patients), followed by stomatitis (3 patients).
Adjuvant chemotherapy with FAM for 6 months for gastric carcinoma indicated comparable RFS and OS with an acceptable toxicity profile.
European Journal of Surgical Oncology 10/2007; 33(7):843-8. · 2.50 Impact Factor
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M H Ryu,
Y K Kang,
S J Jang,
T W Kim,
H Lee,
J S Kim,
Y H Park,
S S Lee,
B Y Ryoo, H M Chang,
J L Lee,
J H Yook,
B S Kim,
J S Lee
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ABSTRACT: Mutation of c-kit is a relatively early event in the tumorigenesis of gastrointestinal stromal tumours (GISTs). The aim was to determine the prognostic significance of p53 alterations as an additional genetic change in GISTs.
We reviewed 125 patients with localized GISTs subjected to complete resection between 1990 and 2002. Mutational analyses of c-kit exons 9, 11, 13 and 17, p53 exons 4-8 and immunohistochemistry for p53 protein were conducted using paraffin-embedded tissues. Alterations of p53 were observed in 50 patients (40.0%). Based on the National Institutes of Health's risk category, p53 alterations were noted more frequently in the higher risk categories (P = 0.041). With a median follow-up of 56.5 months (range: 2.3-126.8), 5-year relapse-free survival (RFS) rates were 61.7% without p53 alterations, compared with only 40.2% with p53 alterations (P = 0.009). Multivariate analysis indicated that p53 alterations comprised an independent, poor prognostic factor for RFS, in addition to c-kit mutations, large size, a high mitotic count and non-gastric primary sites.
Alterations in p53 were more commonly observed in localized GISTs at higher risk of relapse. This suggests that they are significant as an independent, poor prognostic factor.
Histopathology 10/2007; 51(3):379-89. · 3.08 Impact Factor
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D H Koo, H M Chang,
J Y Jung,
J H Song,
J L Lee,
M H Ryu,
T W Kim,
J H Yook,
J S Song,
J S Lee,
Y K Kang
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ABSTRACT: The most common metastatic sites from gastric cancer are the liver, intra-abdominal lymph nodes, ovary and peritoneal cavity. Cutaneous metastasis of gastric cancer is rare, and most cutaneous metastases are typically solitary, nodular, have a firm consistency, and are red or hyperpigmented. Thus, cutaneous metastasis is easily distinguished from other skin disease. We report a case of a 60-year-old woman with cutaneous metastasis of gastric cancer, whose facial skin showed painless pruritic eczema, resembling acute dermatitis. She had earlier undergone a total gastrectomy for advanced gastric cancer in our hospital. After 14 months, she developed eczematous facial lesions; the presumptive diagnosis was acute dermatitis. However, skin biopsy unexpectedly revealed cutaneous metastasis of gastric cancer. After 6 months of systemic chemotherapy with capecitabine and cisplatin, the cutaneous metastasis was markedly improved and a clinically complete remission was accomplished.
Clinical and Experimental Dermatology 06/2007; 32(3):284-6. · 1.20 Impact Factor
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ABSTRACT: This study was performed to assess in the accurate evaluation of primary colorectal carcinoma using PET/CT.
One hundred patients with primary colorectal carcinoma were evaluated during 2004. All patients underwent PET/CT when their preoperative serum carcinoembryonic antigen was >or=10 ng/mL or when CT showed equivocal findings. The appropriateness of PET/CT-induced changes was noted by subsequent operative findings and follow-up.
PET/CT more detected 15 intra-abdominal metastatic lesions than abdomino-pelvic CT scan. PET/CT showed true negative findings in 13 patients and false positive or negative findings in 10. Due to PET/CT results, management plans were altered in 27 patients; 9 had inter-modality changes, 10 received more extensive surgery, and 8 avoided unnecessary procedures.
PET/CT altered management plan in 24% of patients with primary colorectal carcinoma in correct direction. These findings suggest that PET/CT should be considered a part of standard work up for preoperative evaluation in a subset of patients with colorectal carcinoma.
European Journal of Surgical Oncology 11/2006; 32(9):941-7. · 2.50 Impact Factor
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ABSTRACT: To evaluate the efficacy and safety of capecitabine and cisplatin in patients with recurrent gastric cancer after fluoropyrimidine-based adjuvant therapy. Patients with histologically confirmed and measurable advanced gastric cancer that had relapsed after fluoropyrimidine-based adjuvant chemotherapy received oral capecitabine (1250 mg m(-2) twice daily, days 1-14) and intravenous cisplatin (60 mg m(-2) over 1 h, day 1) every 3 weeks. In total, 32 patients were enrolled, of whom 30 were evaluable for efficacy and 32 for safety. A median of 5 cycles (range 1-10) was administered. One patient achieved a complete response and eight had partial responses, giving an overall response rate of 28% (95% CI, 13-44%). The median time to progression and median overall survival were 5.8 months (95% CI, 4.1-7.5 months) and 11.2 months (95% CI, 5.5-16.9 months), respectively. Grade 3 neutropenia and thrombocytopenia were observed in 38 and 6% of patients, respectively. Grade 2/3 nonhaematological toxicities included diarrhoea (19%), stomatitis (19%) and hand-foot syndrome (31%). No grade 4 toxicity, neutropenic fever or treatment-related deaths occurred. Capecitabine in combination with cisplatin was effective and well tolerated as first-line treatment in patients with recurrent gastric cancer after fluoropyrimidine-based adjuvant chemotherapy.
British Journal of Cancer 02/2005; 92(2):246-51. · 5.04 Impact Factor
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Y Hwu,
W L Tsai, H M Chang,
H I Yeh,
P C Hsu,
Y C Yang,
Y T Su,
H L Tsai,
G M Chow,
P C Ho,
S C Li,
H O Moser,
P Yang,
S K Seol,
C C Kim,
J H Je,
E Stefanekova,
A Groso,
G Margaritondo
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ABSTRACT: Can individual cells, including live cells, be imaged using hard x rays? Common wisdom until now required sophisticated staining techniques for this task. We show instead that individual cells and cell details can be detected in culture solution and tissues with no staining and no other contrast-enhancing preparation. The sample examined can be much thicker than for many other microscopy techniques without sacrificing the capability to resolve cells. The key factor in our approach is the use of a coherent synchrotron source and of contrast mechanisms based on the refractive index. The first successful tests were conducted on a variety of cell systems including skin and internal leaf cells, mouse neurons, rabbit fibroblast cells, and human tumor cells.
Biophysical Journal 01/2005; 87(6):4180-7. · 3.65 Impact Factor
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ABSTRACT: There are few studies reporting survival or recurrence patterns in colorectal cancer patients with inferior mesenteric lymph node metastasis (IMLN+). The present study evaluated the prognostic significance of patients being IMLN+ or IMLN- in colorectal cancer.
Survival, recurrence pattern and treatment protocols were compared between 63 IMLN+ patients and 108 IMLN- patients with stage III and IV rectal and sigmoid cancer undergoing curative surgery. Lymph node sampling was routinely performed prior to inferior mesenteric artery ligation and excision flush with aorta. Limited principal node dissection including IMLN was performed in cases of identified node metastasis.
The 5-year disease-free survival rates were 50% in IMLN- and 31% in IMLN+ patients (P=0.004). The 5-year disease-free survival rate was greater in the N1 group than the N2 group (P=0.038). Cox regression analysis showed IMLN+, lymphovascular tumour invasion, T4, M1, and pre-operative serum CEA level over 6 ng/ml were independently associated with unfavorable disease-free survival. The prognostic significance of M category was greater when the IMLN+ was included in the M1 as opposed to the N category. In patients undergoing absolute curative surgery, post-operative recurrence rates were 34% for IMLN- and 57% for IMLN+ patients (P=0.009; OR, 2.611; 95% CI, 1.313-5.194). For IMLN+ patients, post-operative adjuvant treatment independently correlated with disease-free survival (P=0.029).
IMLN+ is an independent survival factor enhancing the prognostic significance of the M category in the AJCC staging. Curative radical surgery and post-operative chemoradiotherapy appears to be warranted for IMLN+ colorectal cancer patients as it resulted in 5-year disease-free survival rates of up to 31% compared to 50% in IMLN- patients.
European Journal of Surgical Oncology 05/2004; 30(3):271-9. · 2.50 Impact Factor
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ABSTRACT: A phase II study was conducted to assess the efficacy and tolerability of substituting capecitabine for 5-fluorouracil in combination with cisplatin in patients with advanced biliary cancer.
Patients with previously untreated metastatic or unresectable measurable biliary adenocarcinoma received oral capecitabine 1250 mg/m(2) twice daily on days 1-14, and intravenous cisplatin 60 mg/m(2) on day 1. This cycle was repeated every 21 days.
Forty-two patients were enrolled in this study. Of these, 38 were assessable for efficacy and 41 were assessable for safety. A median of three cycles of treatment (range one to eight) were administered. One patient achieved a complete response, and eight had partial responses, giving an overall response rate of 21.4% in the intention-to-treat population (95% confidence interval 9.1% to 33.9%). The median response duration was 5.1 months. The median time to progression and median overall survival were 3.7 and 9.1 months, respectively. The most common grade 3/4 adverse events were neutropenia (20% of patients), vomiting (12%), diarrhea (7%) and stomatitis (5%). There were no treatment-related deaths.
The combination of capecitabine and cisplatin has promising antitumor activity and is well tolerated in patients with advanced biliary cancer.
Annals of Oncology 08/2003; 14(7):1115-20. · 6.43 Impact Factor
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ABSTRACT: A phase II study was conducted to assess the efficacy and tolerability of combination therapy with capecitabine and cisplatin in patients with advanced gastric cancer.
Patients with previously untreated metastatic or unresectable measurable gastric adenocarcinoma received oral capecitabine 1250 mg/m(2) twice daily, days 1-14, and i.v. cisplatin 60 mg/m(2) on day 1. This cycle was repeated every 3 weeks.
Forty-two patients were enrolled in this study. Of these, 38 patients were assessable for efficacy and 40 were assessable for toxicity. One patient achieved a complete response and 22 patients had partial responses, giving an overall response rate of 54.8% in the intention-to-treat population (95% confidence interval 39.8% to 69.8%). The median time to progression was 6.3 months and the median overall survival was 10.1 months. The principal adverse events were neutropenia and hand-foot syndrome. Grade 3/4 adverse events were neutropenia (32.5% of patients), thrombocytopenia (10%), stomatitis (2.5%) and diarrhea (5%). Grade 2 and 3 hand-foot syndrome occurred in 20% and 7.5% of patients, respectively. There were no treatment-related deaths.
The combination of capecitabine and cisplatin is active and well tolerated in patients with advanced gastric cancer.
Annals of Oncology 01/2003; 13(12):1893-8. · 6.43 Impact Factor
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ABSTRACT: A phase III single-center randomized trial was performed in order to determine whether the addition of mitomycin C (MMC) and/or doxorubicin to 5-fluorouracil (5-FU) as adjuvant chemotherapy could influence survival in patients with curatively resected gastric cancer.
A total of 416 patients who had undergone curative resection for stage IB-IIIB gastric adenocarcinoma were stratified according to the stage and type of surgery, and then randomized to receive one of the three chemotherapy regimens, 5-FU alone (F) or 5-FU and MMC (FM) or 5-FU, doxorubicin and MMC (FAM) within 5 weeks after surgery.
Of 416 patients registered, 395 (133 in F, 131 in FM and 131 in FAM) were assessable. Median follow-up duration was 91 months. Five-year overall survival rates were 67.2% for F, 67.0% for FM and 66.7% for FAM (P = 0.97). Five-year disease-free survival rates were 62.1% for F, 63.3% for FM and 62.5% for FAM (P = 0.83). Hematological toxicities were more frequent in the FM and FAM groups, whereas stomatitis was more common in the F group.
Compared with adjuvant 5-FU alone, the addition of MMC and/or doxorubicin to 5-FU did not influence survival in patients with resected gastric cancer.
Annals of Oncology 12/2002; 13(11):1779-85. · 6.43 Impact Factor
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ABSTRACT: From January 1990 to December 1997, 53 Korean patients with chronic myeloid leukemia (CML) receiving bone marrow transplantation (BMT) from human leucocyte antigen (HLA)-identical sibling donors conditioned with either busulfan and cyclophosphamide (BU/CY regimen) or total body irradiation and cyclophosphamide (TBI/CY regimen) were compared retrospectively. Transplantation-related mortality was 19% in BU/CY and 12% in TBI/CY, and early death (<100 d) occurred in 3 patients conditioned with BU/CY. Grade II-IV acute graft-versus-host disease (GVHD) was 9% of BU/CY and 52% of TBI/CY patients. Overall incidence of chronic GVHD was 50% of BU/CY and 52% of TBI/CY patients. In patients with chronic phase, 5-yr overall survival was 73% in the BU/CY group compared with 87% in the TBI/CY group (p=NS), and overall disease-free survival was 75% in the BU/CY group and 59% in the TBI/CY group (p=NS). So far, with a median follow-up of 45 months, 11 patients have relapsed; three relapses occurred after BU/CY and 8 after TBI/CY. The actuarial 5-yr relapse rate was 15% after BU/CY, 34% after TBI/CY (p=0.46). For patients transplanted in chronic phase within 1 yr after diagnosis, there was a clear trend for a lower relapse rate in the BU/CY group (5-yr relapse rate 0%) compared with the TBI/CY group (5-yr relapse rate 30%). The BU/CY group had similar BMT-related toxicity and similar overall survival and showed a clear trend of low relapse compared with the TBI/CY group. Therefore, BU/CY is an acceptable alternative for patients with CML during HLA-identical sibling allogeneic BMT.
Clinical Transplantation 06/2001; 15(3):167-72. · 1.67 Impact Factor
