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Jin Won Kim,
Seock-Ah Im,
Miso Kim, Yongjun Cha,
Kyung-Hun Lee,
Bhumsuk Keam,
Min A Kim,
Sae-Won Han,
Do-Youn Oh,
Tae-You Kim,
Woo Ho Kim,
Yung-Jue Bang
[show abstract]
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ABSTRACT: We aimed to clarify the prognostic significance of HER2 positivity in advanced gastric cancer.
The cohort included patients with initially metastatic or recurrent gastric cancer treated with first-line modified FOLFOX-6. The HER2 status was analyzed according to modified scoring criteria specific for gastric cancer.
HER2 positivity was shown in 10 out of 114 patients (9.0%). The median time-to-progression (TTP) (4.3 months, 95% confidence interval (CI)=3.6-4.9) and the overall survival (OS) (7.5 months, 95% CI=6.1-8.8) of patients with HER2-positive gastric cancer tended to be shorter than the median TTP (5.9 months, 95% CI=4.5-7.2) and OS (10.8 months, 95% CI=9.2-12.3) of those with HER2-negative gastric cancer (TTP, p=0.177; OS, p=0.068). Particularly in the subgroup of patients without diffuse-type histology, HER2-positive gastric cancer had a worse TTP than those with HER2-negative gastric cancer (p=0.024). In multivariate analysis of this subgroup, HER2 positivity and ECOG performance status of 2 were associated with shorter TTP (hazard ratio (HR)=2.926, p=0.014; HR=2.489, p=0.035, respectively).
HER2-positive gastric cancer seems to confer poorer prognosis, particularly in patients without diffuse-type tumor, treated with modified FOLFOX-6.
Anticancer research 04/2012; 32(4):1547-53. · 1.73 Impact Factor
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Sae-Won Han, Yongjun Cha,
Agnes Paquet,
Weidong Huang,
Jodi Weidler,
Yolanda Lie,
Thomas Sherwood,
Michael Bates,
Mojgan Haddad,
In Hae Park,
Do-Youn Oh,
Keun Seok Lee,
Seock-Ah Im,
Yung-Jue Bang,
Jungsil Ro,
Tae-You Kim
[show abstract]
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ABSTRACT: Lapatinib plus capecitabine is an effective treatment option for trastuzumab-refractory HER2-positive metastatic breast cancer. We have investigated the correlation between quantitative measures of HER2, p95HER2, and HER3 and treatment outcomes using lapatinib and capecitabine.
Total HER2 (H2T), p95HER2 (p95), and total HER3 (H3T) expression were quantified in formalin-fixed paraffin-embedded samples using the VeraTag assays. Patients received lapatinib and capecitabine treatment following trastuzumab failure according to the Lapatinib Expanded Access Program. The association between the protein expression levels and clinical outcomes was analyzed.
A total of 52 patients were evaluable. H2T level was significantly higher in responders (median 93.49 in partial response, 47.66 in stable disease, and 17.27 in progressive disease; p = 0.020). Longer time-to-progression (TTP) was observed in patients with high H2T [p = 0.018, median 5.2 months in high (>14.95) vs. 1.8 in low (<14.95)] and high H3T [p = 0.017, median 5.0 months in high (>0.605) vs. 2.2 in low (<0.605)]. Patients having both high H2T and high H3T had significantly longer TTP [adjusted hazard ratio (HR) 0.38 (95% CI 0.20-0.73), p = 0.004] and overall survival [adjusted HR 0.46 (95% CI 0.24-0.89), p = 0.020]. No significant association between p95 and response or survival was observed.
These data suggest a correlation between high HER2 and high HER3 expression and treatment outcome, while no significant difference was observed between clinical outcome and p95 expression level in this cohort of HER2-positive, trastuzumab-refractory metastatic breast cancer patients treated with lapatinib and capecitabine.
PLoS ONE 01/2012; 7(7):e39943. · 4.09 Impact Factor
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Jin Won Kim, Yongjun Cha,
Su-Jung Kim,
Sae-Won Han,
Do-Youn Oh,
Se-Hoon Lee,
Dong-Wan Kim,
Seock-Ah Im,
Tae-You Kim,
Dae Seog Heo,
Yung-Jue Bang
[show abstract]
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ABSTRACT: The study aims to determine whether or not oral mucositis (OM) during active chemotherapy in patients with solid tumors is representative of the patient's quality of life (QOL) and the suffering from adverse effects.
From October 2007 to September 2008, we prospectively enrolled 344 consecutive patients with solid tumors who initiated a new chemotherapy regimen. OM, other adverse effects, and the QOL were surveyed by face-to-face interviews and patient diaries.
OM developed during 175 of 633 cycles (27.7%). Forty-five percent of the patients experienced OM during two cycles of chemotherapy. The QOL in patients with OM was significantly lower than patients without OM, as evaluated by the Functional Assessment of Cancer Therapy-General (70.26 ± 15.36 and 75.09 ± 13.12, respectively; p < 0.001). Specifically, the physical and emotional well-being was lower in patients with OM compared with patients without OM. Moreover, other adverse effects were more frequent in chemotherapy cycles with OM compared with chemotherapy cycles without OM (amount of food intake, activity, nausea, vomiting, fever, myalgias, and sensory neuropathy; p < 0.001, p = 0.008, p < 0.001, p = 0.001, p = 0.002, p < 0.001, and p < 0.001, respectively).
OM represents poor QOL and is a basic symptom of symptom clusters in patients with solid tumors receiving active chemotherapy.
Supportive Care in Cancer 03/2011; 20(2):395-403. · 2.09 Impact Factor
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Jiyoung Rhee,
Sae-Won Han, Yongjun Cha,
Hye Seon Ham,
Hwang-phill Kim,
Do-Youn Oh,
Seock-Ah Im,
Jong-Wan Park,
Jungsil Ro,
Keun Seok Lee,
In Hae Park,
Young-Hyuck Im,
Yung-Jue Bang,
Tae-You Kim
[show abstract]
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ABSTRACT: Lapatinib and capecitabine combination therapy is effective in trastuzumab-resistant human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We investigated the biomarkers from serum of patients receiving lapatinib and capecitabine Patients received lapatinib 1,250 mg once daily and capecitabine 2,000 mg/m(2)/day, day 1-14, every 3 weeks. Serum samples were obtained before treatment initiation. Levels of transforming growth factor-α (TGF-α), epidermal growth factor (EGF), extracellular domains of EGFR and HER2 were measured by enzyme-linked immunosorbent assay. The effect of TGF-α on in vitro sensitivity of SK-BR-3 cells to lapatinib was investigated. Sixty-four patients were included. Response rate was significantly higher in patients with low serum TGF-α (≤ 3.75 pg/ml) compared to high TGF-α (>3.75 pg/ml) [61.1% (11/18) vs. 17.4% (8/46), respectively; P = 0.001]. Low serum TGF-α was independently associated with better response in multivariate analysis [adjusted odds ratio, 8.96; 95% confidence interval (CI) 2.4-34.2]. Time-to-progression tended to be shorter in patients with high serum TGF-α compared to low TGF-α [median 3.8 months (95% CI 2.3-5.4) vs. 6.5 (95% CI 6.1-6.8), respectively; P = 0.067]. We confirmed that TGF-α diminished the sensitivity of SK-BR3-cells to lapatinib in vitro. The in vitro antiproliferative effect of cetuximab in combination with lapatinib was higher than that of lapatinib alone in SK-BR3-cells exposed to TGF-α. These data suggest that TGF-α plays a role in resistance to lapatinib and capecitabine therapy among HER2-positive breast cancer.
Breast Cancer Research and Treatment 10/2010; 125(1):107-14. · 4.43 Impact Factor
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Do-Youn Oh, Yongjun Cha,
In-Sil Choi,
So-Young Yoon,
In Keun Choi,
Jee Hyun Kim,
Sang Cheul Oh,
Chang Duck Kim,
Jae Sun Kim,
Yung-Jue Bang,
Yeul Hong Kim
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ABSTRACT: To confirm the efficacy and toxicity of gemcitabine and S-1 combination chemotherapy when used as a first-line therapy in patients with unresectable pancreatic cancer.
Patients with locally advanced or metastatic or recurrent pancreatic adenocarcinoma, which was histologically or cytologically proven, with at least one measurable lesion were eligible for the study. Gemcitabine at a dose of 1,000 mg/m2 was intravenously given over 30 min on days 1 and 8, while S-1 at a dose of 40 mg/m2 was orally given twice daily from day 1 to 14, and the cycle was repeated every 3 weeks. The objective response rate, which was assessed according to RECIST criteria, was the primary end point.
A total of 38 patients were enrolled between June 2006 and June 2007. The median number of treatment courses was 5.5 (range 1-22). Thirty-four patients were evaluable for response. Although no complete response was seen, partial responses were achieved in 11 patients, resulting in an overall response rate of 32% [95% confidence interval (CI) 17-48%]. The median response duration was 6.0 months (95% CI 4.6-8.3 months), the median time-to-progression was 5.4 months (95% CI 2.9-8.0 months), and the median overall survival was 8.4 months (95% CI 5.7-11.1 months). The major grade 3/4 hematologic toxicities were neutropenia (39.5%), leukopenia (15.8%), thrombocytopenia (2.6%), and anemia (7.9%). The major grade 3/4 non-hematologic toxicities included anorexia (10.5%), stomatitis (2.6%), rash (7.9%), fatigue (7.9%) and hyperbilirubinemia (5.3%).
Gemcitabine and S-1 combination chemotherapy was effective and tolerable in patients with unresectable pancreatic cancer.
Cancer Chemotherapy and Pharmacology 08/2009; 65(3):527-36. · 2.83 Impact Factor
