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Mark H Lee

Publications and source records attributed to Mark H Lee.

At least 19 recordsLinked to original sources
PubMed2007

Adhesion of MC3T3-E1 cells to RGD peptides of different flanking residues: detachment strength and correlation with long-term cellular function.

We synthesized a series of RGD peptides and immobilized them to an amine-functional self-assembled monolayer using a modified maleimide-based conjugate technique that minimizes nonspecific interactions. Using a spinning disc apparatus, a trend in the detachment strength (tau(50)) of RGD peptides of different flanking residues was found: RGDSPK > RGDSVVYGLR approximately RGDS > RGES. Using blocking monoclonal antibodies, cellular adhesion to the peptides was shown to be primarily alpha(v)-integrin-mediated. In contrast, the tau(50) value of the cells on fibronectin (Fn)-coated substrates of similar surface density was 6-7 times higher and involved both alpha(5)beta(1) and alpha(v)beta(3) integrins. Cellular spreading was enhanced on RGD peptides after 1 h when compared to RGE and unmodified substrates. However, no significant differences were observed between the different RGD peptides. Long-term function of MC3T3-E1 cells was also evaluated by measuring alkaline phosphatase (ALP) activity and mineral deposition. Among the four peptides, RGDSPK exhibited the highest level of ALP activity after 11 days and mineralization after 15 days and reached comparable levels as Fn substrates after 15 and 24 days, respectively. These findings collectively illustrate both the advantages and limitations of enhancing cellular adhesion and function by the design of RGD peptides.

Amino Acid Sequence↗
PubMed2005

Effect of biomaterial surface properties on fibronectin-alpha5beta1 integrin interaction and cellular attachment.

The ability of fibronectin (Fn) to mediate cell adhesion through binding to alpha(5)beta(1) integrins is dependent on the conditions of its adsorption to the surface. Using a model system of alkylsilane SAMs with different functional groups (X=OH, COOH, NH(2) and CH(3)) and an erythroleukemia cell line expressing a single integrin (alpha(5)beta(1)), the effect of surface properties on the cellular adhesion with adsorbed Fn layers was investigated. (125)I-labeled Fn, a modified biochemical cross-linking/extraction technique and a spinning disc apparatus were combined to quantify the Fn adsorption, integrin binding and adhesion strength, respectively. This methodology allows for a binding equilibrium analysis that more closely reflects cellular adhesion found in stable tissue constructs in vivo. Differences in detachment strength and integrin binding were explained in terms of changes in the adhesion constant (psi, related to affinity) and binding efficiency of the adsorbed Fn for the alpha(5)beta(1) integrins (CH(3) approximately NH(2)<COOH approximately OH) and the resulting average bond strength. Fn interacted more strongly with alpha(5)beta(1) integrins when adsorbed on COOH vs. OH surfaces suggesting that negative charge may be a critical component of inducing efficient cellular adhesion. As evident by the low psi values, Fn adsorbed on NH(2) and CH(3) surfaces interacted inefficiently with alpha(5)beta(1) integrins and also possessed significant non-specific components to adhesion. Lastly, comparison of cellular adhesion to Fn adsorbed onto smooth and rough surfaces showed that nano-scale roughness altered cellular adhesion by increasing the surface density of adsorbed Fn.

Biocompatible Materials↗
PubMed2005

Infused CD34+ cell dose predicts long-term survival in acute myelogenous leukemia patients who received allogeneic bone marrow transplantation from matched sibling donors in first complete remission.

Allogeneic stem cell transplantation (ASCT) has improved the outcome of acute myelogenous leukemia (AML). To further improve the treatment outcome of ASCT in AML, finding a modifiable prognostic factor is mandatory. We evaluated the effect of CD34(+) cell dose on survival in allogeneic bone marrow transplantation (BMT) from HLA-matched sibling donors for AML patients in first complete remission (CR1). The 99 patients included in our analysis were classified into high CD34(+) cell dose group (CD34(+) cells > or = 2.5 x 10(6)/kg) and low CD34(+) cell dose group (CD34(+) cells < 2.5 x 10(6)/kg). The high CD34(+) cell dose patients had better overall survival (5-year overall survival rate, 75% +/- 6% vs 52% +/- 9%; P = .01) and leukemia-free survival (5-year leukemia-free survival rate, 70% +/- 6% vs 44% +/- 9%; P = .04). CD34(+) cell dose was the only independent prognostic factor in overall survival and leukemia-free survival. The high CD34(+) cell dose group had a lower relapse incidence with a borderline statistical significance (5-year relapse rate, 27% +/- 6% vs 50% +/- 10%; P = .09). There were no differences in the engraftment of neutrophil and platelet, grade II-IV acute graft-versus-host disease (GVHD), extensive-stage chronic GVHD, and transplant-related mortality between the high and low CD34(+) cell dose groups. We confirmed that high CD34(+) cell dose favorably affects the outcomes in allogeneic BMT for AML. The effort to attain a high CD34(+) cell dose should be pursued during bone marrow harvest in allogeneic BMT for AML in CR1.

Adolescent↗
PubMed2005

The effect of non-specific interactions on cellular adhesion using model surfaces.

The contribution of non-specific interactions between cells and model functional surfaces was measured using a spinning disc apparatus. These model functional surfaces were created using self-assembled monolayers (SAM) of alkylsilanes terminated with epoxide, carboxyl (COOH), amine (NH(2)), and methyl (CH(3)) groups. These SAMs were characterized using ellipsometry, atomic force microscopy, contact angle goniometry, and X-ray photoelectron spectroscopy to confirm the presence of well-formed monolayers of expected physicochemical characteristics. All substrates also demonstrated excellent stability under prolonged exposure (up to 18 h) to aqueous conditions. The adhesion strength of K100 erythroleukemia cells to the functional substrates followed the trend: CH(3) < COOH approximately epoxide << NH(2). The NH(2) SAM surface exhibited nearly an order of magnitude greater adhesion strength than the other SAMs and this non-specific effect exceeded the adhesion measured when RGD tri-peptides were also immobilized on the surface. These findings illustrate the importance of substrate selection in quantitative studies of peptide-mediated cellular adhesion.

Adsorption↗
PubMed2005

Extranodal nasal type NK/T-cell lymphoma: elucidating clinical prognostic factors for risk-based stratification of therapy.

The purpose of this study was to define distinctive clinical features of "nasal" and "nasal-type" NK/T cell lymphomas by assessing prognostic factors. The anatomic definition of extranasal NK/T cell lymphoma has been vague resulting in variable definitions of extranasal sites by different groups. We analysed the clinical behavior of 90 NK/T cell lymphoma patients and attempted to elucidate the prognostic factors for risk-based stratification of therapy. We observed no significant difference between "nasal" and "nasal-type" NK/T cell lymphomas in regards to clinical features and survival using the conventional anatomic classification. We suggest the categorisation of the two subtypes of NK/T cell lymphoma as follows: UNKTL (upper aerodigestive tract NK/T cell lymphoma) including all lymphomas confined to nasal cavity, nasopharynx, and the upper aerodigestive tract and EUNKTL (extra-upper aerodigestive tract NK/T cell lymphoma) group to include all sites other than the UNKTL group. The EUNKTL group in this study had advanced stage at diagnosis, higher LDH, higher IPI score, poorer performance and inferior response to the anthracycline-based chemotherapy with statistical significance. There was a significant difference in survival rate between EUNKTL and UNKTL group (20.0%, 54.0%, respectively, P = 0.0068). More aggressive treatment should be sought for this particular group of patients for EUNKTL patients.

Adult↗
PubMed2005

Influential factors for the collection of peripheral blood stem cells and engraftment in acute myeloid leukemia patients in first complete remission.

Although several studies have investigated factors influencing peripheral blood stem cell (PBSC) mobilization in patients with nonmyeloid malignancies in an effort to increase the efficiency of autologous PBSC transplantation (APBSCT), there are very few reports on the efficiency of PBSC mobilization in patients with leukemia. We analyzed the effects of influential variables on successful mobilization and the correlation between infused cell doses and engraftment in acute myeloid leukemia (AML) patients in first complete remission (CR1) who received APBSCT. Between May 1998 and May 2003, 34 patients with AML underwent APBSC collections at our institution. All patients were in CR1 at the time of transplantation. Except for 1 patient, all patients successfully achieved the target CD34(+) cell yield of > or = 2 x 10(6)/kg. Among progenitor cells, the CD34(+) cell dose and the colony-forming unit-granulocyte-macrophage count showed significant correlations with neutrophil and platelet engraftments. The time to neutrophil engraftment was inversely correlated to the number of infused CD34(+) cells (r = -0.67; P < .001), whereas the time to neutrophil engraftment was not significantly correlated with the number of monocytes (r = 0.20; P = .701) or the number of nucleated cells (r = 0.35; P = .062). The time to platelet engraftment was significantly correlated with the dose of infused CD34(+) cells (r = -0.47; P = .012). The univariate analysis showed that more CD34(+) cells per kilogram and more CD34(+) cells per kilogram per day were collected from patients who had a shorter interval (less than 2 months) between diagnosis and PBSC harvest (P = .0111). In conclusion, this study showed that the CD34(+) cell dose was most strongly correlated with a successful engraftment in AML CR1 patients who underwent APBSCT. The proper timing of PBSC collections should be explored to optimize the outcome of APBSCT in AML CR1 patients.

Adolescent↗
PubMed2004

L-ascorbic acid represses constitutive activation of NF-kappaB and COX-2 expression in human acute myeloid leukemia, HL-60.

There is increasing evidence that L-ascorbic acid (LAA) is selectively toxic to some types of cancer cells at pharmacological concentrations, functioning as a pro-oxidant rather than as an anti-oxidant. However, the molecular mechanisms by which LAA initiates cellular signaling leading to cell death are still unclear. In an effort to gain insight into these mechanisms, the effects of LAA on eukaryotic transcription nuclear factor NF-kappaB and cyclooxygenase-2 (COX-2) expression were investigated. In the present study, LAA suppressed DNA binding activity of NF-kappaB, composed of a p65/p50 heterodimer, through inhibition of degradation of inhibitory kappaB-alpha (IkappaB-alpha) and prevention of nuclear translocation of p65. The inhibitory effect of LAA on NF-kappaB activity was dependent upon glutathione levels in HL-60 cells, as well as generation of H2O2 but not superoxide anion. LAA also downregulated the expression of COX-2, which has a NF-kappaB binding site on its promoter, through repressing NF-kappaB DNA binding activity. Moreover, cotreatment of 1 microM arsenic trioxide (As2O3) with various concentrations of LAA enhanced an LAA-induced repression of NF-kappaB activity and COX-2 expression. In conclusion, our data suggest that LAA exerts its anti-tumor activity through downregulation of NF-kappaB activity and COX-2 expression, and these inhibitory effects can be enhanced by co-treatment with As2O3.

Apoptosis↗
PubMed2004

Phase II study of doxorubicin and cisplatin in patients with metastatic hepatocellular carcinoma.

OBJECTIVE: The outcome of systemic chemotherapy in metastatic hepatocellular carcinoma (HCC) patients had been disappointing. Based on the demonstrated antitumor activities and different mechanisms of action and toxicity profiles, we designed a phase II trial of combination therapy with doxorubicin and cisplatin in metastatic HCC patients anticipating a synergistic interaction of the combination. METHODS: From January 1998 to January 2003, 42 consecutive patients with metastatic HCC were accrued. The regimen consisted of doxorubicin 60 mg/m2 delivered as an intravenous infusion over 30 min on day 1, followed by cisplatin 60 mg/m2 infused over 1 h on day 1. The cycle was repeated every 28 days. The objective tumor response was evaluated after two or three courses of chemotherapy. The serum alpha-fetoprotein level was measured at the start of every cycle. RESULTS: In total, 122 cycles of the regimen were administered, with a median of three cycles per patient (range one to eight cycles). The median age of the patients was 45 years (range 19-61 years), and 37 were evaluable for treatment response. The objective response rate was 18.9% (95% CI 8.0-35%) with one complete response and six partial responses. Six patients (16.2%) had stable disease and 24 patients (64.9%) had progression. Median overall survival of 37 patients was 7.3 months (95% CI 5.9-8.6 months). The median time to progression of all evaluable patients was 6.6 months (95% CI 5.4-7.8 months). Of 37 evaluable patients, 12 32.4%, 95% CI 18.0-49.8%) showed more than 50% decrease in AFP level from their baseline AFP and the median time to decrease in AFP by more than 50% was 1.8 months with a range of 0.7-4.7 months. The chemotherapy was well tolerated and the most common grade 3/4 side effects were neutropenia (14.3%), thrombocytopenia (11.9%), and diarrhea (9.5%). CONCLUSION: Combination chemotherapy with doxorubicin and cisplatin in metastatic HCC patients showed modest antitumor activity with relatively tolerable adverse effects. The objective response rate of the regimen was comparable to those found in other phase II trials, but the search for the optimal chemotherapy should be continued.

Adult↗
PubMed2004

Gefitinib (ZD1839) monotherapy as a salvage regimen for previously treated advanced non-small cell lung cancer.

PURPOSE: A worldwide compassionate-use program has enabled >42,000 patients with advanced non-small cell lung cancer (NSCLC) to receive gefitinib treatment. Here we report the outcome of gefitinib therapy in patients who enrolled in the "Iressa" Expanded Access Program at the Samsung Medical Center. EXPERIMENTAL DESIGN: Patients with advanced or metastatic NSCLC who had progressed after prior systemic chemotherapy and for whom no other treatment option was available were eligible to receive gefitinib treatment as part of the Expanded Access Program. A post hoc assessment of potential prognostic factors for response and survival was performed by multivariate analysis. RESULTS: All 111 evaluable patients had stage IV disease; most patients had a baseline performance status of 2 [n = 52 (47%)] or 3 [n = 18 (16%)] and had received >/=2 prior chemotherapy regimens (56%). The objective response rate was 26%, the disease control rate (measured over >/=8 weeks) was 40%, and the 1-year survival rate was 44%. Adenocarcinoma histology was associated with better response and disease control rates, and a performance status of 0-2 was also associated with a better disease control rate. Both of these factors, as well as female gender, were significantly associated with longer survival. Gefitinib was well tolerated; the most common adverse event was grade 1 skin rash. CONCLUSIONS: Gefitinib demonstrated significant antitumor activity and a favorable tolerability profile in this series of NSCLC patients with poor prognosis.

Adult↗
PubMed2004

Intestinal lymphoma: exploration of the prognostic factors and the optimal treatment.

Primary gastrointestinal (GI) lymphoma accounts for 4% to 20% of all non-Hodgkin's lymphomas (NHL), being the most common extranodal site of presentation. However, the optimal management of intestinal lymphoma has not yet been established. During the period of 1994 to 2001, we retrospectively analyzed the clinical features of 67 intestinal lymphoma patients diagnosed according to the Lewin's definitions. The most frequently involved location was ileocecal (35.8%) followed by small bowel (31.3%), large bowel (19.4%), and multiple GI involvement (13.4%). The estimated 5-year overall survival rate was 53%. Out of all treated patients, 49.2% achieved complete response. The advanced stage, poor performance and T-cell phenotype had an adverse prognostic influence on overall survival. In localized diseases (stage 1 and 2), the primary surgical treatment had the most favorable influence on failure-free survival (P < 0.05). The resection of localized intestinal lymphoma may be appropriate as the primary treatment.

Aged↗
PubMed2004

Extrapulmonary small-cell carcinoma: a single-institution experience.

BACKGROUND: Extrapulmonary small-cell carcinoma (EPSCC) has been recognized as a clinicopathological entity distinct from small-cell carcinoma (SCC) of the lung. This study aimed to review the clinical features, therapy and natural course of patients with EPSCC in Oriental single-institution series. METHODS: We retrospectively reviewed the medical records of patients with SCC between September 1995 and December 2002. Study eligibility required that patients had pathologically proven SCC in sites other than lung and normal radiological findings of the chest and normal sputum cytology or negative bronchoscopic findings. RESULTS: Twenty-four patients with EPSCC were identified and primary sites were various: uterine cervix in seven (29%), urinary bladder in five, colon or rectum in three, kidney in two and stomach, esophagus, pancreas, common bile duct, larynx, parotid gland, thymus in one each. Sixteen patients (66.7%) had limited disease (LD) and eight had extensive disease (ED). Patients with ED received mostly platinum-based chemotherapy, for which the response rate was 57%, but showed an aggressive natural history, with median overall survival (OS) of 9.2 months. Patients with LD were treated with a variety of therapeutic modalities. LD SCC of the cervix showed a favorable clinical course, with five patients being disease-free with a median follow-up of 28.4 months. Patients with LD SCC of sites other than cervix had an aggressive course with a median OS of 9.6 months. CONCLUSION: EPSCC was identified in various sites, with the most common primary site being the uterine cervix. Regardless of the primary site or disease stage, EPSCC of sites other than cervix was usually a fatal disease with a discouraging outcome for various treatment modalities.

Adult↗
PubMed2004

Primary pulmonary non-Hodgkin's lymphoma.

BACKGROUND: Primary pulmonary non-Hodgkin's lymphoma is a very rare neoplasm. It is represented most commonly by marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. Although there have been a few reviews of this lymphoma, clinical features, diagnostic procedure, optimal management and prognostic factors have not been well defined. METHODS: We reviewed the medical records of 24 patients who were pathologically and clinically diagnosed as primary pulmonary lymphoma between September 1995 and June 2003. RESULTS: There were 13 patients with MALT lymphoma and two with MALT lymphoma accompanied by large B-cell lymphoma, seven with diffuse large B-cell lymphoma and two with anaplastic large cell lymphoma. Half the patients were asymptomatic at presentation; 46% had respiratory symptoms and 16.7% had B-symptoms. Initial radiological findings were variable including nodules, masses, infiltrates or consolidation. The majority of patients (66.7%) needed surgical approaches (open thoracotomy or video-assisted thoracoscopy) for definite diagnosis. Bronchoscopy was performed in 83%, but only 30% showed a diagnostic yield. The 13 patients with MALT lymphoma were treated with a variety of modalities such as observation, surgery and single or combination chemotherapy, and combination chemotherapy was administered to 11 patients with non-MALT lymphoma regardless of surgery. The overall survival rate at 3 years for all 24 patients was 86% with a median follow-up of 32 months. CONCLUSION: Although this entity of lymphoma appears to have a good prognosis, further clinical experience and long-term follow-up are needed to identify prognostic factors.

Bronchoscopy↗
PubMed2004

Docetaxel plus cisplatin as second-line therapy in metastatic or recurrent advanced gastric cancer progressing on 5-fluorouracil-based regimen.

The purpose of this study was to determine the activity and safety of docetaxel plus cisplatin as second-line chemotherapy for advanced gastric cancer. This trial included patients who had failed first-line chemotherapy with a 5-fluorouracil regimen within 1 year before their enrollment. After registration, patients were treated with docetaxel intravenously at a dose of 60 mg/m2 given over 1 hour followed by cisplatin 60 mg/m2 given over 2 hours. The treatment was continued every 3 weeks until disease progression or unacceptable toxicity was detected. Forty-three patients were registered and 41 were assessable for response. Seven partial responses were observed (17.1% of the "evaluable" patients; 95% confidence interval [CI], 0-29) with a median response duration of 3.9 months. Stable disease was documented in 2 cases (4.9%). The median survival was 5.8 months (95% CI, 3.4-8.3), resulting in a 1-year survival rate of 23%. Tolerance was acceptable, with the main toxicity being neutropenia. The authors conclude that second-line chemotherapy with docetaxel plus cisplatin for advanced gastric cancer is feasible with an acceptable toxicity level.

Adenocarcinoma↗
PubMed2004

Phase II study of gemcitabine combined with uracil-tegafur in metastatic pancreatic cancer.

OBJECTIVE: The single agent gemcitabine is the standard first-line treatment for advanced pancreatic cancer. Recent studies of a combination of gemcitabine and 5-fluorouracil (5-FU) revealed that survival data were superior to those with gemcitabine or 5-FU alone. The administration of oral uracil-tegafur (UFT) is more convenient and simulates the effect of a continuous or protracted infusion of 5-FU. Therefore, we conducted a phase II study of gemcitabine combined with UFT in metastatic pancreatic cancer patients and assessed the efficacy and the toxicity of the regimen. METHODS: Twenty-two pancreatic adenocarcinoma patients (18 males, 4 females) were enrolled from December 2000 to September 2002. The regimen consisted of gemcitabine 1,000 mg/m(2) once weekly for 3 consecutive weeks, and oral UFT 390 mg/m(2)/day (in 3 divided doses) on days 1-14. The cycle was repeated every 28 days. The objective tumor response was evaluated after 2 courses of chemotherapy. RESULTS: 82 cycles were administered in total, with a median of 3 cycles per patient (range 1-6 cycles). The median age was 52 years (range 28-69 years). Response to treatment could be assessed in all patients. The objective response rate was 22.7% (95% CI, 7.8-45.4) with no complete response and 5 partial responses. Four patients (18.2%) had stable disease and 13 patients (59.1%) had a progression. The median time to progression was 4.2 months (range 0.9-13.6). The median overall survival was 5.8 months (range 0.5-13.6). Of 10 patients eligible for the assessment of clinical benefit response, 4 (40%, 95% CI 12.2-73.8) showed clinical benefit. Among 21 patients with baseline CA 19-9 levels, CA 19-9 was reduced by 50% or more in 12 patients (57.1%). The chemotherapy was generally well tolerated and the most common grade 3-4 toxic side effects were neutropenia (18.2%), anemia (4.5%), and diarrhea (4.5%). CONCLUSIONS: The combination chemotherapy with gemcitabine and UFT in metastatic pancreatic cancer was tolerable for most patients but showed modest response rates and clinical benefit. However, a randomized phase III study should be conducted in order to further test the efficacy of the regimen.

Adenocarcinoma↗
PubMed2004

Tuberculosis in hematopoietic stem cell transplant recipients in Korea.

Hematopoietic stem cell transplantation (HSCT) results in impaired cell-mediated immunity, which subsequently increases the risk of infection from bacterial, fungal, and viral pathogens. Mycobacterial infections are commonly seen in immunodeficient patients, especially in endemic areas. Several series that have reviewed mycobacterial infections in HSCT patients reported incidences varying from less than 0.1% to 5.5%. From February 1996 to July 2003, we retrospectively reviewed records of 295 adult patients who underwent HSCT at Samsung Medical Center, Korea. Mycobacterial infections were diagnosed in 9 (3.1%) of the 295 transplant recipients. The time from HSCT to tuberculosis (TB) infection ranged from 45 days to 165 days posttransplantation. Analysis at the univariate level indicated that a conditioning regimen with total body irradiation (TBI), chronic graft-versus-host disease, and a previous history of TB infection were significant risk factors for the development of TB infection after HSCT. Multivariate analysis revealed that only a previous history of TB infection and TBI increased the risk of TB infection in HSCT patients (relative risk, 4.8 and 12.5, respectively). Isoniazid prophylaxis in HSCT recipients with only radiologic findings suggestive of past inactive TB infection did not significantly alter the incidence of TB infections (P = .236). In conclusion, a previous history of active TB infection and TBI were significant risk factors of TB infection following HSCT, and isoniazid prophylaxis may benefit HSCT recipients with a previous history of active TB infection.

Adult↗
PubMed2003

Arsenic trioxide inhibits the growth of A498 renal cell carcinoma cells via cell cycle arrest or apoptosis.

Previously, we showed that arsenic trioxide potently inhibited the growth of myeloma cells and head and neck cancer cells. Here, we demonstrate that arsenic trioxide inhibited the proliferation of all the renal cell carcinoma cell lines (ACHN, A498, Caki-2, Cos-7, and Renca) except only one cell line (Caki-1) with IC(50) of about 2.5-10 microM. Arsenic trioxide induced a G(1) or a G(2)-M phase arrest in these cells. When we examined the effects of this drug on A498 cells, arsenic trioxide (2.5 microM) decreased the levels of CDK2, CDK6, cyclin D1, cyclin E, and cyclin A proteins. Although p21 protein was not increased by arsenic trioxide, this drug markedly enhanced the binding of p21 with CDK2. In addition, the activities of CDK2- and CDK6-associated kinase were reduced in association with hypophosphorylation of Rb protein. Arsenic trioxide (10 microM) also induced apoptosis in A498 cells. Apoptotic process of A498 cells was associated with the changes of Bcl-(XL), caspase-9, caspase-3, and caspase-7 proteins as well as mitochondria transmembrane potential (Deltapsi(m)) loss. Taken together, these results demonstrate that arsenic trioxide inhibits the growth of renal cell carcinoma cells via cell cycle arrest or apoptosis.

Animals↗
PubMed2003

A phase II trial of concurrent chemoradiation therapy followed by consolidation chemotherapy with oral etoposide and cisplatin for locally advanced inoperable non-small cell lung cancers.

We report a phase II study to evaluate the survival rate, response rate and toxicity of concurrent chemoradiation therapy (CCRT) followed by consolidation chemotherapy (CT) with oral etoposide and cisplatin for patients with locally advanced inoperable non-small cell lung cancer (NSCLC). Fifty-four patients with locally advanced inoperable NSCLC who had received no prior therapy were enrolled into this trial between May 1995 and December 2000. Treatment consisted of two cycles of concurrent CT and four cycles of consolidation CT with oral etoposide (50 mg/m2) on days 1-14 during the CCRT courses and on days 1-21 during the consolidation CT courses, plus cisplatin (75 mg/m2 i.v.) on day 1 of a 28-day cycle. Conventional radiotherapy (1.8 Gy/fraction, 63 Gy over 7 weeks) was delivered from day 1 of the CT. Fifty-two patients were evaluable for response. Twelve patients (22%) achieved complete responses, and 32 patients (60%) achieved partial responses, for an overall response rate of 82% with a median duration of response of 9.1 months. Forty-three per cent developed grade 4 haematological toxicity, 11% grade 3 or 4 oesophagitis and 7% grade 3 or 4 lung toxicity. There were two treatment-related deaths, one from radiation pneumonitis and the other from sepsis. After a median follow-up duration of 50 months (range 20-85), the median overall survival time was 15.3 months (95% CI, 9.7-20.8), and the 1-, 2-, 3-, and 5 year overall survival rates were 62, 40, 30 and 16%, respectively. The duration of median progression-free survival was 12.3 months (95% CI, 7.4-17.3), and the 1-, 2-, 3-, and 5-year progression-free survival rates were 47, 40, 29 and 23%, respectively. Thus, concurrent conventional chest radiotherapy with oral etoposide plus cisplatin followed by consolidation CT led to an encouraging survival rate and prolongation of the time to progression, with moderate toxicity in patients with locally advanced inoperable NSCLC.

Administration, Oral↗
PubMed2003

Early concurrent chemoradiotherapy with prolonged oral etoposide and cisplatin for limited-stage small-cell lung cancer.

BACKGROUND: Combined chemoradiotherapy (CRT) is the standard treatment modality for limited-stage small-cell lung cancer (LSCLC), but the optimal timing of radiation is controversial. Prolonged oral etoposide has the advantage of prolonged exposure, which possibly leads to improved clinical outcome. We conducted a phase II trial of early concurrent CRT, starting from the very beginning of the first cycle of chemotherapy for previously untreated LSCLC. METHODS: Chemotherapy was given for six cycles, each consisting of oral etoposide (50 mg/m(2) daily from day 1 to 14) and intravenous cisplatin (75 mg/m(2) on day 1), every 3 weeks. Thoracic radiation therapy was given from day 1 of the first cycle of chemotherapy, administered at 2.0 Gy in 22 daily fractions to a total dose of 44 Gy. RESULTS: Forty-four patients were enrolled. The median age was 60 years (range, 42-77 years), including 15 patients (34%) over 65 years-of-age. We observed a complete response rate of 52% (95% CI, 37-67%), and an overall response rate of 88% in an intent-to-treat (ITT) analysis. Median overall survival was 14.9 months (95% CI, 11.4-18.3 months) and the median time to progression was 10.8 months (95% CI, 9.3-12.4 months) for the ITT population. In 220 cycles, grade 3-4 neutropenia was observed in 48% of cycles and grade 3-4 thrombocytopenia in 30% of cycles. Neutropenic fever was observed in 18 patients (41%). CONCLUSIONS: Early concurrent CRT, starting from the very beginning of the first cycle of chemotherapy with prolonged oral etoposide and cisplatin failed to show any improvement in survival compared with other CRT regimens.

Administration, Oral↗