-
[show abstract]
[hide abstract]
ABSTRACT: A retrospective analysis of treatment outcomes in patients with nasopharyngeal carcinoma (NPC) was performed in which the newly revised 1997 American Joint Committee on Cancer (AJCC) stage classification was applied and compared with the 1988 AJCC and Ho stage classifications, with emphasis on the predictive value of different staging systems in determining failure patterns in NPC.
Three hundred and twenty-four patients with newly diagnosed NPC treated between September 1989 and August 1991 and originally staged according to Ho stage classification were re-staged according to the 1988 and 1997 AJCC stage classifications. In addition to stage grouping, patients were also classified into the following prognostic categories to study the failure patterns: early disease group (T1-2N0-1), advanced local disease group (T3-4N0-1), advanced nodal disease group (T1-2N2-3), and advanced locoregional disease group (T3-4N2-3). The overall survival (OAS), relapse-free survival (RFS), local relapse-free survival, nodal relapse-free survival, and distant metastases-free survival were compared among different stage groups and prognostic categories in the three staging systems.
In the new AJCC system, the percentages of patients with Stage I, II, III, and IV disease were 15.1%, 31.5%, 28.1%, and 25.3%, respectively, whereas most patients were classified as having Stage IV disease (65.7%) in the old AJCC system and Stage II or III disease (74.1%) in the Ho system. The 5 year OAS rates in the 1997 AJCC Stage I, II, III, and IV disease were 97.7%, 78.7%, 79.5%, and 61.4%, respectively. The corresponding 5 year RFS rates were 95.7%, 64.7%, 54.5%, and 41.1%. Using the 1997 AJCC system to define the four prognostic categories, the early disease group had the lowest incidence of relapse (27.6%) and death (18.4%), whereas the advanced locoregional disease group had the highest incidence of relapse (61.4%) and death (43.2%). Both the advanced local disease group and the advanced nodal disease group had similar rates of relapse (46.7% vs. 47.2%), but local relapse was the major cause of failure in the former group (61.8%), whereas distant metastases was the major cause in the latter group (44%).
Using the 1997 AJCC staging system, the authors observed a better distribution of patient numbers as well as segregation of survival curves among different stage groups. Moreover, prognostic categories with distinct prognosis and failure patterns were definable by the new system, which has important implications in selecting appropriate patient treatment strategies.
Cancer 01/2002; 92(11):2845-55. · 4.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the efficacy of afterloading brachytherapy following radical neck dissection (RND) in the management of extensive cervical lymph node disease in nasopharyngeal carcinoma after radiotherapy; and to examine prospectively prognostic factors and the pathologic behavior of neck disease.
Twenty-seven patients with nasopharyngeal carcinoma who had extensive cervical lymph node metastasis following external radiotherapy were treated with RND. Thirteen of them also underwent afterloading brachytherapy with iridium wire (Ir 192). The RND specimens of the 27 patients were also examined with step serial whole-specimen sectioning.
All patients survived and their wounds healed primarily. Pathologic examination revealed 183 tumor-bearing lymph nodes that contained tumors in the neck: level I, 4% (8/183); level II, 53% (96/183); level III, 34% (62/183); level IV, 5% (9/183); and level V, 4% (8/183). Extracapsular tumor extension was seen in 84% of patients. Multivariate analysis identified the number of tumor-bearing lymph nodes detected in the specimens to be the only significant factor that affected control of disease. Although the neck disease in the group of patients who had afterloading brachytherapy was more extensive, the 3-year actuarial tumor control for the groups with and without brachytherapy were 60% and 61%, respectively.
Recurrent cervical lymph nodes after radiotherapy in nasopharyngeal carcinoma are extensive and RND is mandatory for a successful salvage. When the nodal metastasis infiltrate or adhere to surrounding tissue, afterloading brachytherapy with iridium wire can provide satisfactory local tumor control.
Archives of Otolaryngology - Head and Neck Surgery 01/2002; 127(12):1457-62. · 1.63 Impact Factor
-
D Chua,
J Huang,
B Zheng,
S Y Lau,
W Luk,
D L Kwong, J S Sham,
D Moss,
K Y Yuen,
S W Im,
M H Ng
[show abstract]
[hide abstract]
ABSTRACT: Tumor cells from NPC patients are regularly and latently infected with EBV. To examine whether the virus serves as target for immune intervention of the cancer, we determined levels of EBV-specific CTLp in peripheral blood from NPC patients, long-term survivors of the cancer and healthy subjects. CTLp levels of test subjects varied between 3- 3,000/10(6) PBMCs. The plasma EBV burden increased when the CTLp level fell below 150, whereas the EBV burden of PBMCs was not correlated with CTLp level. Compared with healthy carriers, CTLp levels of patients were lower and varied over a wider range, between 3-1,500/10(6) PBMCs. The quantitative immune deficit was probably attributed to the tumor because, first, CTLp in survivors was restored to levels similar to those in healthy carriers after the tumor had been successfully treated. Second, the CTLp level changed as disease progressed, being lower in local disease, increased in locoregional disease and decreased again when the tumor metastasized. Based on these findings, 4 patients with advanced disease were infused with 5 x 10(7)-3 x 10(8) autologous EBV CTLs. The treatment was safe and unaccompanied by inflammatory or other complications, but whether it improved tumor control could not be discerned from the large tumor bulk. Nevertheless, the treatment regularly increased CTLp levels of patients, maintained it at higher levels for protracted periods and, in 3 patients, restored host surveillance of EBV replication, reducing the plasma EBV burden. Taken together, these results provided a rationale to further explore EBV as a target of immune intervention of NPC.
International Journal of Cancer 11/2001; 94(1):73-80. · 5.44 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To study the efficacy of stereotactic radiosurgery in salvaging early-stage persistent and recurrent nasopharyngeal carcinoma (NPC) after primary radiotherapy.
A prospective single-arm study evaluating the response and outcome of patients with rT1-2 NPC treated by stereotactic radiosurgery. Eleven patients with rT1-2 were treated by radiosurgery between March 1998 and March 2000. Four patients were treated for persistent disease occurring within 4 months after primary radiotherapy, six were treated for first recurrence, and one for third recurrence. Six patients had rT1 disease and five had rT2 disease. Most patients had disease not amenable to brachytherapy, surgery, or external re-irradiation. The median target volume was 5.8 cc (range, 3.3-16.9). Radiosurgery was performed with multiple noncoplanar arcs of photon, with a median dose of 12.5 Gy delivered to the 80% isodose line (range, 12-14 Gy). Median follow-up time after radiosurgery was 18 months (range, 9-30).
Nine patients had complete regression of tumor as assessed by imaging, nasopharyngoscopy, and biopsy; one patient had partial regression of tumor; whereas one patient had static disease. The overall response rate was 91% (10 of 11) and the complete response rate was 82% (9 of 11). Two patients with complete response subsequently had local relapse develop, with one recurrence outside the treated volume 8 months after radiosurgery, and the other within the treated volume 6 months after radiosurgery. One patient with a partial response had neck node recurrence develop. Temporal lobe necrosis occurred in one patient but probably represents sequelae of primary radiation after reviewing the dosimetry. Ten patients are still alive, whereas one patient with local relapse had distant metastases develop and died. The estimated 1-year local control rate after radiosurgery was 82%.
Our preliminary results indicate that stereotactic radiosurgery is an effective treatment modality for persistent and recurrent T1-T2 NPC, and early control rate seems to be comparable to other salvage treatments. More clinical experiences and longer follow-up are still needed to validate our results and to address fully the role of radiosurgery in salvaging local failures of NPC.
Head & Neck 10/2001; 23(9):791-8. · 2.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Nasopharyngeal carcinoma (NPC) is highly prevalent in southern China. Prominent acute side effects of radiotherapy create problems in daily living and working that can generate considerable financial difficulties. A better adjustment to a diagnosis of NPC appears to be associated with an improved rate of recovery, a better quality of life (QoL), a quicker return to work, and normal functioning. Patient satisfaction with physician consultation and the way information is provided in particular may have significant bearing on QoL. The current study reports on short-term QoL after radiotherapy in NPC patients as a function of satisfaction with the information provided.
Newly referred Hong Kong Chinese NPC patients (n = 211) completed interview measures at baseline before the initiation of radiotherapy, at 4 months after baseline (immediate posttreatment consultation) (FU 1), and again at 8 months (short-term postradiation period) after baseline (FU 2). Satisfaction with the information provided was measured by five items selected from the cognitive subscale of the Medical Interview Satisfaction Scale (MISS). QoL was measured by the Chinese version of the Functional Assessment of Cancer Therapy-General Scale (FACT-G (Ch)).
After adjustment for overall patient satisfaction (the PSQ-9), optimism, worry about family, anger, eating ability, subjective health, family income, and occupation at FU 1, treatment between baseline and FU 1, and disease recurrence after baseline, the 5-item MISS at FU 1 (beta = 0.21, P < 0.01) was found to significantly predict patient QoL at FU 2. Adjustment for baseline QoL and disease stage did not appear to alter this relation (beta = 0.20, P < 0.01).
To the authors' knowledge, there is very little research concerning NPC. The results of the current study reinforced the need to improve physicians' information provision during consultations with Chinese NPC patients shortly after the end of treatment.
Cancer 10/2001; 92(8):2126-35. · 4.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Contemporary imaging with endoscopic examination determines tumor extent and this is reflected in the revised staging system. Radiotherapy remains the primary treatment modality. The use of intensity-modulated radiotherapy aims at enhanced tumor control while reducing adverse effects. Concurrent chemotherapy has shown to improve survival, although its efficacy in endemic regions requires confirmation. Determination of circulating cell-free Epstein-Barr virus DNA might detect early recurrence. For patients who developed recurrence in the neck, surgery provides good salvage. For small tumor in the nasopharynx, good results can be obtained with reirradiation therapy, brachytherapy or surgery. The salvage option depends on the size and location of the tumor as well as the expertise available. The long-term effects of these treatment modalities might be significant.
Expert Review of Anti-infective Therapy 07/2001; 1(1):134-41. · 2.65 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Amplification of 3q25-q26 was one of the most frequent chromosomal alterations in human ovarian carcinoma. A chromosome microdissection-hybrid selection method was applied to isolate transcribed sequences from a primary ovarian cancer containing high-copy-number amplification of 3q26 using 3q26 band-specific DNAs generated by chromosome microdissection. Using this method, we have isolated a novel candidate oncogene eIF-5A2 (eukaryotic initiation factor 5A2). eIF-5A2 shares 82% identity of amino acid sequence with eIF-5A including the minimum domain needed for eIF-5A maturation by hypusine modification at lysine-50 residue. Amplification and overexpression of eIF-5A2 was frequently detected in primary ovarian cancers and ovarian cancer cell lines. The proliferation-related function of eIF-5A supports that eIF-5A2 is a candidate oncogene related to the development of ovarian cancer.
Cancer Research 06/2001; 61(9):3806-9. · 7.86 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Peripheral gammadelta T cells derived from healthy donors were found to exhibit cytotoxicity against a variety of tumor cell lines in vitro, including CNE2, which was established from nasopharyngeal carcinoma (NPC). The anti-tumor effects were further studied in a mouse model. Control nude mice inoculated s.c. with 5 x 10(6) CNE2 cells regularly developed hypodermal tumors, which progressively increased in size, and animals had a mean survival of 35 +/- 3.4 days. Tumor growth was arrested and tumor size was reduced after animals were infused with 5 x 10(7) gammadelta T cells derived from a healthy donor. The anti-tumor effects were temporary, however, and tumor growth was resumed after about 1 week in a group of the animals that had been given a single dose of gammadelta T cells. In another group of animals given 2 doses of gammadelta cells 1 week apart, resumption of tumor growth was delayed for a further week. Mean survival of the 2 groups was increased to 61 +/- 15.7 and 74 +/- 12.9 days, respectively. Immunohistology revealed an accumulation of infused cells in tumors attended by focal tumor necrosis in specimens taken 2 days after infusion. Infiltrative cells virtually disappeared from tumor tissues 6 days after infusion, accompanied by increased mitotic indices of tumor cells. These temporal relationships suggested that the accumulation of infused gammadelta T cells in hypodermal tumors was responsible for the observed anti-tumor effects.
International Journal of Cancer 06/2001; 92(3):421-5. · 5.44 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Our center contributed 183 patients to the Asian-Oceanian Clinical Oncology Association (AOCOA) multicenter randomized trial comparing induction chemotherapy (CT) followed by radiotherapy (RT) vs. RT alone in patients with locoregionally advanced undifferentiated nasopharyngeal carcinoma (NPC). In a preliminary report no difference in terms of overall survival or relapse-free survival was found between the 2 treatment arms. To study the long-term outcome and patterns of failure after CT for NPC, we analyzed our own center data for which a uniform radiation treatment protocol was adopted and a longer follow-up time was available.
Between September 1989 and August 1993, a total of 183 patients were recruited into the AOCOA randomized study from our center. Patients with newly diagnosed NPC of Ho's T3 disease, N2-N3 disease, or with neck node size of at least 3 cm were eligible. Stratification was made according to the nodal size (< or = 3 cm, >3- 6 cm, > 6 cm). Patients were randomized to receive 2-3 cycles of CT with cisplatin 60 mg/m(2) and epirubicin 110 mg/m(2) D1 followed by RT or RT alone. Four patients were excluded from the current analysis (2 died before treatment, 2 received treatment elsewhere). The remaining 179 patients were randomized to the two treatment arms, with 92 to the CT arm and 87 to the RT arm. Two patients in the CT arm had RT only, and all patients completed radiation treatment. Overall survival (OAS), relapse-free survival (RFS), local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), and distant metastases-free survival (DMFS) were analyzed using Kaplan--Meier method and significance of survival curve differences calculated using log--rank test. Analysis was performed based on the intent-to-treat.
The median follow-up was 70 months. At the time of analysis, 50% of patients in the CT arm and 61% in the RT arm had relapse, while 32% in the CT arm and 36% in the RT arm had died of the disease. The median RFS was 83 months in the CT arm and 37 months in the RT arm. The median OAS has not yet been reached for both arms. No significant differences were found for the various endpoints, although there was a trend suggesting better nodal control in the CT arm. The 5-year rates for the various endpoints in the CT arm vs. the RT arm were: 53% vs. 42% for RFS (p = 0.13), 70% vs. 67% for OAS (p = 0.68), 80% vs. 77% for LRFS (p = 0.73), 89% vs. 80% for NRFS (p = 0.079), and 70% vs. 68% for DMFS (p = 0.59). There was also no significant difference in the patterns of failure between both arms: in the CT arm, 28% of failures were local only, 13% regional only, 4% locoregional, 44% distant, and 11% mixed locoregional and distant. In the RT arm, 23% of failures were local only, 13% regional only, 11% locoregional, 43% distant, and 9% mixed locoregional and distant.
Induction chemotherapy with the regimen used in the current study did not improve the treatment outcome or alter the failure patterns in patients with locoregionally advanced NPC, although there was a trend suggesting better nodal control in the combined modality arm. Alternative strategies of combining chemotherapy and radiotherapy should be tested and employed instead.
International Journal of Radiation OncologyBiologyPhysics 04/2001; 49(5):1219-28. · 4.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Brachytherapy is useful for the reirradiation of nasopharyngeal carcinoma. In the current study, the long term treatment results of permanent radioactive gold(198) grain interstitial implantation in patients with persistent and recurrent nasopharyngeal carcinoma were reviewed.
Gold grain implantation was performed under direct vision with a split palate approach to provide 60 grays (Gy) 0.5 cm away from the plane of implantation. Between August 1986 and May 1999, 106 patients were treated with gold grain implantation (45 patients for persistent disease, 53 patients for first recurrence, and 8 patients for second recurrence in the nasopharynx). All patients had histologically proven disease by biopsy before undergoing implantation.
Patients with persistent disease and those with first recurrence did well with the gold grain implantation. The 5-year local control rates for patients with persistent disease, first recurrence, and second recurrence in the nasopharynx were 87.2%, 62.7%, and 23.4%, respectively (P = 0.0004). The 5-year metastasis free survival rates were 68.1%, 60.3%, and 40%, respectively, for the 3 groups (P = 0.048). The overall survival rates at 5 years for the 3 groups were 79.1%, 53.6%, and 42.9%, respectively (P = 0.0047). Patients with computed tomography evidence of disease extension outside the nasopharynx had a lower local control rate compared with patients whose disease was confined to the nasopharynx (5-year local control rate of 52% vs. 72.3%; P = 0.031). The size of the lesion was not found to be an independent prognostic factor for local control after implantation. Multivariate analysis showed only an indication for implantation (persistent disease, first recurrence, and second recurrence) to be a significant prognostic factor for local control. Complications attributed to gold grain implantation included headache, palatal fistula, and mucosal radiation necrosis at the site of implantation, and were reported to occur in 28.3%, 18.9%, and 16%, respectively, of patients.
For selected patients with disease confined to the nasopharynx, gold grain implantation is an effective salvage treatment for persistent and recurrent nasopharyngeal carcinoma.
Cancer 04/2001; 91(6):1105-13. · 4.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The endoscopic and histologic findings before and after radiotherapy (RT) for nasopharyngeal carcinoma (NPC) were correlated to study the sensitivity and specificity of endoscopic findings in predicting histologic results. The efficiacy of endoscopic examination and post-RT multiple site biopsies in detecting persistent disease was also evaluated.
Seven hundred forty-six patients were evaluated. Pre-RT, biopsies were taken from both sides of the nasopharynx to assess the extent of tumor. Four to 16 weeks after RT, routine six-site biopsy specimens were taken from both roofs, lateral, and posterior walls of the nasopharynx and repeated 2 weeks later. Endoscopic findings of exophytic growth, nodule, ulcer, and submucosal bulge were considered "residual tumor," others were considered "no residual tumor." Persistent disease was defined as positive histologic findings 12 weeks after RT.
Before RT, sensitivity of endoscopic findings and biopsy specimens in detecting malignancy were 99.7% and 94.2%, respectively. After RT, sensitivity and specificity of endoscopic findings in predicting positive histologic findings were 29% and 85.8%, respectively, with a positive predictive value of 34.9% and a negative predictive value of 82.2%. Of positive histologic findings, 27.7% were missed in the first session of biopsies; 33.5% of those with positive histologic findings turned out to have persistent disease. For prediction of persistent disease, the sensitivity and specificity of endoscopic findings were 40.4% and 84.4%, with a positive predictive value of 16.3% and a negative predictive value of 95%, and that of histologic findings in the first session of biopsies were 59.6% and 88.3%, respectively, with a positive predictive value of 27.7% and a negative predictive value of 96.7%.
Endoscopic findings alone have low sensitivity in predicting persistent disease, multiple sites biopsy specimens are indicated. Because only 1.9% of patients with endoscopic findings of "no residual tumor" and negative histologic findings in first session of biopsies had persistent disease, this group can be spared second biopsies. Repeat biopsies are indicated for those with endoscopic findings of "residual tumor" or positive histologic findings in first session of biopsies to improve detection of persistent disease.
Head & Neck 02/2001; 23(1):34-41. · 2.40 Impact Factor
-
X Y Guan,
S B Fu,
J C Xia,
Y Fang, J S Sham,
B D Du,
H Zhou,
S Lu,
B Q Wang,
Y Z Lin,
Q Liang,
X M Li,
B Du,
X M Ning,
J R Du,
P Li,
J M Trent
[show abstract]
[hide abstract]
ABSTRACT: Comparative genomic hybridization (CGH) has been applied to detect recurrent chromosome alterations in 62 primary gastric carcinomas. Several nonrandom chromosomal changes, including gains of 8q (31 cases, 50%), 20q (29 cases, 47%) with a minimum gain region at 20q11. 2-q12, 13q (21 cases, 34%) with a minimum gain region at 13q22, and 3q (19 cases, 31%) were commonly observed. The regions most frequently lost included: 19p (23 cases, 37%), 17p (21 cases, 33%), and 1p (14 cases, 23%). High copy number gain (DNA sequence amplification) was detected in 6 cases. Amplification of 8q23-q24.2 and 20q11.2-q12 were observed in 3 cases. Gain of 20q and loss of 19p were confirmed by fluorescence in situ hybridization using corresponding bacterial artificial chromosomes (BAC) clones from those regions. The gain and loss of chromosomal regions identified in this study provide candidate regions involved in gastric tumorigenesis.
Cancer Genetics and Cytogenetics 12/2000; 123(1):27-34. · 1.39 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and has a very poor prognosis. Fifty primary HCC cases have been analyzed in the present study to explore the association between genomic alteration in primary HCC and clinical features. Several recurrent chromosomal abnormalities were identified in this study. The most frequently detected chromosomal gains involved chromosome arms 1q (33/50 cases, 66%), 8q (24/50 cases, 48%), and 20q (10/50 cases, 20%). High-copy-number amplifications involving 1q (4 cases), 8q (3 cases), and 20q (3 cases) were detected, and a minimum overlapping amplified region at 1q12-q22 was identified. The most frequently detected loss of chromosomal material involved 16q (35/50 cases, 70%), 17p (26/50 cases, 52%), 19p (21/50 cases, 42%), 4q (20/50 cases, 40%), 1p (18/50 cases, 36%), 8p (16/50 cases, 32%), and 22q (14/50 cases, 28%). The associations between genomic alterations detected in the present study and clinical features including clinical stage, tumor size, HBV infection, chronic liver disease, and liver cirrhosis were explored. Our CGH results suggest that the gain of 20q and deletion of 8p are late genetic alterations in HCC, because the incidence of these alterations was obviously increased in the advanced clinical stages. Another finding showed that loss of 8p and gain of 8q and 20q are associated with tumor size. The recurrent gain and loss of chromosomal regions identified in this study provide candidate regions that may contain oncogenes or tumor suppressor genes respectively involved in HCC development and progression.
Genes Chromosomes and Cancer 11/2000; 29(2):110-6. · 3.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Gossypol, a male contraceptive drug extracted from cottonseeds, has been found to have antiproliferative activity on tumour cells and is thought to be a potential anticancer drug. The aim of this study was to investigate the mechanisms of gossypol-induced cell death on two colon carcinoma cell lines, HT29 and LoVo. Firstly, we studied the effect of gossypol on the colony forming ability of these tumour cells, which is the main target of chemotherapeutic drugs. Using clonogenic assays, flow cytometry and DNA gel electrophoresis techniques, we have found that gossypol not only inhibited colony forming ability of these tumour cells, but we also observed cellular internucleosomal DNA fragmentation in the cells treated with 3 doses of gossypol and this was accompanied by the appearance of a sub-G1 apoptotic peak and morphological characteristics of apoptosis. Our results suggest that the gossypol induced cell death is via an apoptotic pathway and the effect of gossypol may not be cell cycle specific. Using Western blotting analysis, we found that the gossypol-induced apoptosis may not be involved in the regulation of p53 but possibly associated with the regulation of bcl-2 and Bax expression. Our evidence indicates that gossypol may provide a potential therapeutic benefit for the treatment of colon carcinoma and understanding the mechanisms of gossypol-induced cytotoxicity on tumour cells is essential for including this drug in clinical use.
Life Sciences 11/2000; 67(22):2663-71. · 2.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The p16INK4a tumor suppressor gene is frequently inactivated in nasopharyngeal carcinoma (NPC) and hence it may play an important role in the suppression of this tumor. In order to study the effect of p16INK4a restoration in NPC cells, full-length human p16INK4a gene was transfected into a NPC cell line, CNE1. Four individual clones with differential levels of p16INK4a protein expression, were selected for further studies. The introduction of p16INK4a into CNE1 cells induced growth suppression through G0/G1 cell cycle arrest; however, the cell growth rate was not correlated to the levels of p16INK4a protein expression. To study whether transfection of p16INK4a could protect NPC cells from radiation, cisplatin and 5-fluorouracil (5FU), the cellular sensitivity of p16INK4a transfectants and vector control were investigated. An increase in sensitivity to 5FU was observed (2-fold compared to IC50) in all 4 clones compared to vector-transfected control. P16INK4a transfection also resulted in increased sensitivity to cisplatin (1.5-1.8-fold) in 3 out of 4 cell lines. However, no difference in radiosensitivity was found between the p16INK4a transfectants and the control. These findings indicate that p16INK4a suppresses NPC cell growth through G0/G1 arrest and modulating cellular response to chemotherapeutic drugs in NPC cells. Therefore, restoration of p16INK4a may have a therapeutic purpose in the treatment of NPC.
International Journal of Oncology 08/2000; 17(1):135-40. · 2.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to compare the antiemetic efficacy of three 5-HT3 antagonists (granisetron, ondansetron, tropisetron) plus dexamethasone for the prevention of acute emesis induced by high-dose cisplatin chemotherapy. This was a randomized, open label, crossover study. Recruited into the study were 94 chemotherapy-naive patients of whom five were excluded because chemotherapy was not given, noncisplatin regimen was used instead, or presence of anticipatory vomiting. The remaining 89 evaluable patients were mostly (86.5%) male, and were all treated for head and neck cancers. The antiemetic regimens consisted of 1) granisetron 3 mg i.v. and dexamethasone 20 mg i.v. on day 1 (GRADEX); 2) tropisetron 5 mg i.v. and dexamethasone 20 mg i.v. on day 1 (TRODEX); and 3) ondansetron 8 mg i.v. and dexamethasone 20 mg i.v. to be followed by ondansetron 8 mg p.o. x 2 on day 1 (ONDEX). Patients were randomized to receive one of the three regimens in the first cycle, and treatment was crossed over to the other two regimens in subsequent cycles. Antiemetic efficacy was assessed using self-report diaries recording the number of vomiting episodes as well as duration and severity of nausea within the first 24 hours. Complete response was defined as no vomiting with or without mild nausea, and major response was defined as one vomiting episode and/or moderate to severe nausea. Major efficacy refers to either complete or major response. A total of 219 cycles was given to 89 patients: 16 received one cycle only, 16 received two cycles, and 57 received three cycles. No carryover effects were observed between cycles. Using pooled data from all cycles, the complete response rates to GRADEX, TRODEX, and ONDEX were 81%, 68%, and 71%, respectively (p = 0.11); the corresponding major efficacy rates were 91%, 93%, and 86%, respectively (p = 0.36). When only the first cycle was considered, the complete response rates to GRADEX, TRODEX, and ONDEX were 81%, 75%, and 74%, respectively (p = 0.58); the corresponding major efficacy rates were 92%, 94%, and 84%, respectively (p = 0.38). Analysis of the crossover data showed that the majority of patients achieved complete response or major efficacy with the different pairs of regimens, and there were no significant differences between different regimens in terms of complete response or major efficacy. The only exception was GRADEX versus TRODEX, in which 15.5% of patient achieved complete response with GRADEX as compared with 1.7% with TRODEX (p = 0.025). The majority of patients (53%) did not report any preference, whereas 14% preferred GRADEX, 15% preferred TRODEX, and 18% preferred ONDEX. The three 5-HT3 antagonists, when used in combination with steroids, had similar major efficacy for prophylaxis against cisplatin-induced acute emesis. Although GRADEX was superior to TRODEX in terms of complete response, this may not be of clinical significance. The choice of antiemetic regimens should therefore depend on patient preference and drug cost.
American Journal of Clinical Oncology 05/2000; 23(2):185-91. · 2.01 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study was to evaluate the efficacy and toxicity of ifosfamide, 5-fluorouracil (5-FU) and leucovorin (IFL) as a second-line chemotherapy regimen in patients with recurrent undifferentiated nasopharyngeal carcinoma (NPC) previously treated with platinum/5-FU. Between June 1997 and February 1999, 18 patients were entered into the study. 3 patients had loco-regional recurrence, 12 had distant metastases and 3 had both loco-regional recurrence and distant metastases. All patients had previously received platinum/5-FU as adjuvant or palliative treatments. The IFL regimen consisting of ifosfamide 1.2 g/m(2) (with mesna), 5-FU 375 mg/m(2) and leucovorin 20 mg/m(2) for 5 days and was repeated every 21 days. The dose of ifosfamide was escalated to 1.4 and 1.6 g/m(2) in subsequent cycles according to the bone marrow toxicity, and the dose of 5-FU to 450 and 525 mg/m(2) according to the severity of mucositis. Patients received a median of 3 cycles of IFL (range: 2-6), with a median total ifosfamide dose of 21 g/m(2) (range: 13-46) and a median total 5-FU dose of 6.75 g/m(2) (range: 4.1-14.7). The median follow-up was 10 months (range: 4-25). 9 patients (50%) achieved a partial response and 1 patient (6%) achieved a complete response, with an overall response rate of 56% (95% confidence interval (CI): 32-80%). For those patients who responded to IFL, 8 had subsequent disease progression on follow-up, with a median response duration of 7.1 months (95% CI: 5.3-8.9). The median time to progression for all patients was 6.5 months (95% CI: 4.2-8.7). 12 patients are still alive with an estimated 1-year survival probability rate of 51%. Treatments were well tolerated, only 1 patient had grade 3 emesis. None of the patients had grade 3/4 anaemia, leucopenia or thrombocytopenia, although IFL was discontinued in 1 patient because of persisting thrombocytopenia. IFL is an effective second-line regimen in patients with recurrent NPC and is well tolerated with mild toxicity. Combining platinum and IFL in chemonaïve patients may further improve the overall response rate and duration and is worth investigating in future trials.
European Journal of Cancer 05/2000; 36(6):736-41. · 5.54 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Few cancer specific quality-of-life (QoL) measures from the West have been translated for use with Chinese-speaking patients, and no substantial validation of these translations with adequately large cohorts has been published previously, to the authors' knowledge. The Functional Assessment of Cancer Therapy-General (FACT-G) is a well-validated QoL instrument that is specific to cancer patients. The scale was translated into Chinese and the psychometric properties of this translated scale (FACT-G [Ch]) were tested with a Chinese sample in Hong Kong, China.
A total of 1262 Chinese cancer patients were selected in 3 samples from 5 Hong Kong regional hospitals. Quantitative and qualitative data were used to assess the cultural equivalence, factor structure, reliability, and validity of the FACT-G (Ch).
Focus group discussions indicated that the FACT-G was seen as covering QoL domains identified as important and relevant to Chinese cancer patients, though in some respects it was seen as having limited scope in this sample. Psychometrically, the factor structure of the FACT-G deviated from that of the original work. The FACT-G (Ch) had acceptable reliability (Cronbach alpha 0.85). The convergent validity of the FACT-G (Ch) with a generic QoL measure (WHOQOL-BREF[HK]) was 0.72 (P < 0.001), and divergent validity showed low correlations of less than 0.15 (P < 0.05) with non-QoL measures.
Focus group data indicated that the FACT-G translation into Chinese was seen as a conceptually relevant and moderately sufficient QoL measure. Psychometrically, the instrument had acceptable properties, but conceptual differences from the original version were suggested. Although more work is needed to increase its adequacy, the translated scale has reasonable utility for use with Chinese populations in clinical settings.
Cancer 04/2000; 88(7):1715-27. · 4.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The latent membrane protein LMP1 of Epstein-Barr virus (EBV) is often present in EBV-associated malignancies including nasopharyngeal carcinoma and Hodgkin's lymphoma. Previous work demonstrates that the LMP1 gene of EBV is sufficient to transform certain established rodent fibroblast cell lines and to induce the tumorigenicity of some human epithelial cell lines. In addition, LMP1 plays pleiotropic roles in cell growth arrest, differentiation, and apoptosis, depending on the background of the target cells. To examine the roles of LMP1 in cell proliferation and growth regulation in primary culture cells, we constructed a recombinant retrovirus containing an LMP1 gene. With this retrovirus, LMP1 was shown to stimulate the proliferation of primary mouse embryonic fibroblasts (MEF cells). It has a mitogenic activity for MEF cells, as demonstrated by an immediate induction of cell doubling time. In addition, it significantly extends the passage number of MEF cells to more than 30 after retroviral infection, compared with less than 5 for uninfected MEF cells. Furthermore, LMP1 cooperates with a p16-insensitive CDK4(R24C) oncogene in transforming MEF cells. Our results provide the first evidence of the abilities of the LMP1 gene, acting alone, to effectively induce the proliferation of primary MEF cells and of its cooperativity with another cellular oncogene in transforming primary cells.
Journal of Virology 02/2000; 74(2):883-91. · 5.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In a recent study, it was shown that DNA damaging agent cisplatin-induced growth arrest and cell death in cancer cells by a pathway sharing some of the characteristics of replicative senescence. The aim of this study was to determine the role of p53, p21WAF1 and p16INK4A proteins in this alternative route to cancer cell death in additional human cancer cell lines. After exposure to cisplatin, all the cell lines underwent growth arrest and expressed the senescence marker senescence-associated beta-galactosidase, but showed none of the features of apoptosis. However, there was no change in p53 protein expression, and neither p21WAF1 nor p16INK4A was expressed before or up to 4 days after cisplatin exposure. These findings provide further evidence that cells carrying mutations resulting in loss of function in the p53 gene can be killed by cisplatin via a p53-independent route with some similarities to replicative senescence, but not apoptosis.
International Journal of Oncology 01/2000; 15(6):1097-102. · 2.40 Impact Factor
