Biomedical subjects

John F Ensley

Publications and source records attributed to John F Ensley.

At least 19 recordsLinked to original sources

PubMed2006

Benefit of postoperative chemoradiotherapy for patients with unknown primary squamous cell carcinoma of the head and neck.

BACKGROUND: Postopertative adjuvant chemoradiotherapy recently became an established modality for patients with selected high-risk locally advanced head and neck cancers. The optimal treatment of unknown primary squamous cell cancer of the head and neck (SCCHN) continues to be controversial, since major randomized studies excluded those patients. METHODS: We conducted a retrospective review of patients treated during 1995 to 2002 for unknown primary SCCHN. All patients were treated with a neck dissection followed by concurrent high-dose cisplatin (100 mg/m(2)) and bilateral neck radiotherapy. RESULTS: Thirty-seven patients were identified with nodal disease distribution of N1 (5%), N2a (22%), N2b (41%), N2c (8%), N3 (22%), and Nx (3%). Modified neck dissection was done on the majority (30/37 = 81%) of patients. With a median follow-up of 42 months among the survivors, very few patients had regional recurrence (5%) or distant failure (11%), and 89% of patients were alive. The actuarial 5-year overall survival rate could not be estimated because there were no deaths beyond 20 months after surgery. Substantial yet acceptable acute and late morbidities were demonstrated in this cohort of patients. CONCLUSIONS: Postoperative chemoradiotherapy is of potential benefit to patients with unknown primary SCCHN by improving survival and reducing failures. This treatment warrants further prospective evaluation.

Adult↗

PubMed2005

Growth factor-sensitive molecular targets identified in primary and metastatic head and neck squamous cell carcinoma using microarray analysis.

Polypeptide growth factors play key roles in the processes of cell migration and invasion. In this study, we have used cDNA microarrays to identify target genes whose expression is differentially modulated by the growth factors TGFbeta and EGF. HN4 and HN12 cell lines, established from primary tumor and a lymph node metastasis arising in one patient with head and neck squamous cell carcinoma, were treated with 2nM EGF or 50pM TGFbeta for 24h and extracted RNA was used to prepare labeled cDNAs which were hybridized to NCI UniGem 2.0 cDNA microarrays containing 9128 features. Results revealed constitutive overexpression of 41 genes and underexpression of 109 genes in metastatic HN12 compared to HN4 under conditions of serum withdrawal. Furthermore, TGFbeta treatment resulted in relative upregulation of 53 genes and downregulation of 91 genes in HN12 compared with HN4, whereas cells treated with EGF showed relative upregulation of 67 genes and downregulation of 113 genes. Partial overlap was found between TGFbeta and EGF-modulated gene sets. Results were verified for a subset of each category using quantitative PCR, western blotting and zymography. The data indicate that TGFbeta and EGF differentially affect gene expression in primary and metastatic HNSCC cells, and likely contribute to the invasive properties of metastatic cells through regulation of both common and specific mediators for each growth factor.

Blotting, Western↗

PubMed2005

Organ preservation for advanced resectable cancer of the base of tongue and hypopharynx: a Southwest Oncology Group Trial.

PURPOSE: The Southwest Oncology Group designed a phase II trial for patients with base of tongue or hypopharyngeal cancer to evaluate the complete histologic response rate at the primary site after induction chemotherapy followed by chemoradiotherapy for responders. Secondary end points were the rate of organ preservation and the need for salvage surgery. PATIENTS AND METHODS: Fifty-nine eligible patients were enrolled; 37 had base of tongue cancer, and 22 had hypopharynx cancer. Forty-two percent had stage III disease, and 58% had stage IV disease. Induction chemotherapy was two cycles of cisplatin 100 mg/m(2) and fluorouracil 1,000 mg/m(2)/d for 5 days. Patients who had a greater than 50% response at the primary site were treated with radiation 72Gy and concurrent cisplatin 100 mg/m(2) for three cycles. Patients with less than partial response at the primary had immediate salvage surgery. RESULTS: Forty-five patients (76%) had a greater than 50% response at the primary after induction chemotherapy; 43 went on to receive definitive chemoradiotherapy. Thirty-two patients (54%) achieved a histologic complete response at the primary site, and an additional nine patients had a complete clinical response, but biopsy was not done. Seventy-five percent of patients did not require surgery at the primary tumor site. The 3-year overall survival was 64%. The 3-year progression-free survival with organ preservation was 52%. CONCLUSION: Patients with base of tongue or hypopharyngeal cancer treated with this regimen of induction chemotherapy followed by definitive chemoradiotherapy have a good rate of organ preservation without compromise of survival.

Adult↗

PubMed2005

An in vivo evaluation of docetaxel delivered intratumorally in head and neck squamous cell carcinoma.

OBJECTIVE: To identify activity and biological mechanisms of intratumoral (IT) docetaxel on head and neck squamous cell carcinoma (HNSCC). METHODS: Docetaxel IT therapy was tested in xenograft models of 2 HNSCC lines, HN30 and HN12. The overall and disease-free survival rates, tumor growth, and toxic effects were measured. The pharmacokinetic profiles of docetaxel in plasma and tumor were compared after IT and intravenous (IV) administration. Comparisons between common and supradoses of docetaxel with regard to expression of regulators in the cell cycle, apoptosis, and signal transduction pathways were determined using Western blot analysis. RESULTS: In the HN30 and HN12 xenograft models, IT docetaxel improved overall as well as disease-free survival and reversed tumor growth. The only toxic effects noted were local (alopecia and skin breakdown). Skin breakdown resolved in all cases. At equivalent dosing levels, IT docetaxel achieved a 26-fold higher peak tumor concentration and 24-fold longer tumor exposure than IV treatment. Furthermore, limited plasma exposure was noted with IT docetaxel. Supradose levels of docetaxel produced distinct protein expression patterns for regulators of the cell cycle (cyclins A and B, p21, and p27), apoptosis (cleaved caspase-3 and cleaved PARP), and signal transduction (EGFR, pEGFR, pc-Jun, and pERK) in HNSCC, which supports a distinctive mechanism of action for supradose docetaxel levels. Since levels of cleaved caspase-3 and PARP, markers of apoptosis, were only elevated with lower doses, the observed cell death at supradose levels was probably due to necrosis. CONCLUSIONS: Injections of IT docetaxel at usual and supradoses are associated with a pharmacokinetic profile and biological mechanism distinct from those observed with usual IV doses. It is calculated that IT therapy in men will increase peak concentrations of docetaxel in tumors by 1000-fold over the conventional IV dose used clinically. These preclinical results support further testing of IT docetaxel in HNSCC.

Animals↗

PubMed2005

Cellular DNA content parameters as prognostic indicators in human astrocytomas.

OBJECTIVE: Clinical parameters such as grade, size and/or location of the tumor are good predictors of outcome in patients with astrocytoma. The objective of this study was to determine whether DNA content parameters have a prognostic significance for this group of tumors. METHODS: Following optimization and validation of methodology for evaluating cellular DNA content parameters (CDCP), tumor DNA ploidy and percent S phase fraction (SPF) were determined from 64 patients using formalin fixed, paraffin embedded specimens (mean coefficient of variation=4.94) obtained over a 10-year period. Median survival times correlated with grade (I/II=1154 vs. III/IV=483days, P=0.0317). Fifty-five percent of the specimens contained DNA aneuploid (DNA-A) components (average SPF=18.3%) and 45% were DNA diploid (DNA-D) (average SPF=9.6%). Survival did not correlate with overall differences in DNA ploidy (DNA-D=181 vs. DNA-A=206days, P=0.6314) when treated and untreated tumors were analyzed. However, a trend for prolonged median survival was observed in patients whose tumors were untreated with respect to cytotoxic therapy based on DNA ploidy status (DNA-D=275 vs. DNA-A=15days, P=0.3408). Survival for all patients did not correlate with median SPF (<13.5% av.=121 vs. >13.5% av.=154days, P=0.6534). CONCLUSION: DNA content parameters may correlate with the natural history and treatment outcome of newly diagnosed untreated patients with astrocytomas.

Adult↗

PubMed2005

Proteome-wide analysis of head and neck squamous cell carcinomas using laser-capture microdissection and tandem mass spectrometry.

Remarkable progress has been made to identify genes expressed in squamous cell carcinomas of the head and neck (HNSCC). However, limited information is available on their corresponding protein products, whose expression, post-translational modifications, and activity are ultimately responsible for the malignant behavior of this tumor type. We have combined laser-capture microdissection (LCM) with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify proteins expressed in histologically normal squamous epithelium and matching SCC. The protein fraction from approximately 10,000-15,000 normal and tumor cells was solubilized, digested with trypsin, and the resulting peptides were analyzed by LC-MS/MS. Database searching of the resulting sequence information identified 30-55 proteins per sample. Keratins were the most abundant proteins in both normal and tumor tissues. Among the proteins differentially expressed, keratin 13 was much lower in tumors, whereas heat-shock (Hsp) family members were highly expressed in neoplastic cells. Wnt-6 and Wnt-14 were identified in both normal and tumor tissues, respectively, and placental growth factor (PIGF) was detected only in tumors. Immunohistochemical analysis of HNSCC tissues revealed lack of keratin 13 in tumor tissues, and strong staining in normal epithelia, and high expression of Hsp90 in tumors. Our study, by combining LCM and proteomic technologies, underscores the advantages of this approach to investigate complex changes at the protein level in HNSCC, thus complementing existing and emerging genomic technologies. These efforts may likely result in the identification of new biomarkers for HNSCC that can be used to diagnose disease, predict susceptibility, and monitor progression in individual patients.

Aged↗

PubMed2005

Uncoupling of epidermal growth factor-dependent proliferation and invasion in a model of squamous carcinoma progression.

Cell lines pairs were established from a primary squamous carcinoma of tongue and a lymph node metastasis and their biological behavior characterized. HN12 cells, derived from metastatic SCC, formed tumors upon subcutaneous transplantation to athymic mice, whereas HN4, derived from a primary lesion in the same individual, were non-tumorigenic in this assay. EGF stimulated proliferation of HN4 cells; in comparison, not only were metastatic HN12 cells refractory to the stimulatory effects of this growth factor but showed inhibition at higher growth factor concentrations. However, in contrast to the effects on proliferation, EGF (10 ng/ml) readily induced HN12 cells to invade in Boyden chamber assays whereas HN4 were non-invasive under these conditions. The invasive properties of HN12 cells were apparently independent of MMP-2 activity, as levels of active MMP-2 were higher in the non-invasive cells. However, EGF stimulated MMP-9 activity in invasive cells. Additionally, HN12 cells expressed constitutively high levels of active MMP-7 and MMP-3/10. The pharmacological agents LY294002, PD098059, SP600125, or SB202190 inhibited invasion of HN12 cells, suggesting requirement for phosphoinositide 3-OH kinase- and mitogen activated protein kinase-dependent pathways in the process. The data indicate that distinct biochemical differences distinguish metastatic squamous carcinoma cells from those derived from corresponding primary tumors, resulting in their contrasting biological properties.

Animals↗

PubMed2005

Docetaxel associated pathways in cisplatin resistant head and neck squamous cell carcinoma: a pilot study.

PURPOSE: This is a pilot study to identify changes in gene and protein expressions after treatment with docetaxel in cisplatin-resistant head and neck squamous cell carcinoma (HNSCC). METHODS: Two cisplatin-resistant HNSCC cell lines, HN30 and HN12, were treated with either docetaxel or cisplatin. After 48 hours, differential gene expression between the two treatment groups (docetaxel-treated cells and cisplatin-treated cells) was analyzed using cDNA microarray. Differential protein expression between these two treatment groups was determined using PowerBlot and Western Blot analysis RESULTS: A total of 150 genes and proteins were found to have differential expression patterns in HNSCC after treatment with docetaxel versus cisplatin. Many of these differentially expressed genes and proteins were involved in the cell cycle (decreased E2F), apoptosis (increased bax), angiogenesis (increased thrombospondin), and signal transduction (decreased epidermoid growth factor receptor) regulatory pathways. CONCLUSIONS: Gene and protein expression are different and distinct between cells treated with docetaxel and cells treated with cisplatin. This finding provides evidence that different molecular pathways leading to cell death are targeted by docetaxel and cisplatin. Future studies focusing on these differentially expressed genes and proteins may improve our understanding, at the molecular level, of the mechanisms responsible for docetaxel-induced apoptosis in cisplatin-resistant HNSCC. Furthermore, these differentially expressed genes and proteins can be exploited as useful surrogate endpoint biomarkers in future clinical trials using docetaxel.

Antineoplastic Agents↗

PubMed2004

Microsatellite analysis of serum DNA in patients with head and neck cancer.

We have shown previously that microsatellite alterations in serum DNA was predictive of distant metastasis in a study with 21 primary head and neck squamous cell carcinoma patients. To further investigate serum microsatellite alterations as a prognostic tool, we carried out microsatellite analysis of serum DNA with 10 markers on 152 patients with head and neck cancer. Forty-five percent (68/152) of patients had microsatellite alterations of serum DNA identical to corresponding tumor DNA. In 16 patients that had distant metastasis, 11 patients had a positive serum test (microsatellite alterations detectable in their serum DNA with one or more markers). The difference in distant metastasis rates between the negative and positive serum tests (6.0% [5/84] vs. 16.2% [11/68], RR = 2.7) was clinically significant and almost reached statistical significance (p = 0.06). When the analysis was restricted to patients with recurrent disease, a positive serum test correlated with those who developed distant metastasis (p = 0.04). Other parameters, such as development of recurrence, stage of the cancer, disease-free survival and overall survival, were not associated with a positive serum test. Detecting tumor DNA in serum by microsatellite analysis may help identify patients at risk for distant metastasis. Therefore, circulating tumor cells may contribute to the presence of tumor DNA in the serum. In the future if a serum test is positive, therapeutic approaches may by intensified, such as platinum-based chemoradiation, to reduce distant failures.

Carcinoma, Squamous Cell↗

PubMed2004

Cytochrome p450 and glutathione transferase expression in squamous cell cancer.

PURPOSE: The cytochrome P-450 (CYP) and glutathione S-transferase (GST) enzyme systems modulate the carcinogenic effects of tobacco. Therefore, the expression of these enzymes may be in part responsible for the observed interindividual and inter-racial differences in the risk of development of squamous cell carcinoma of the head and neck (SCCHN). The first aim of this study was to evaluate the feasibility of measuring the expression of the CYP and GST in target tissue from the head and neck. The second aim was to compare the expression of CYPs 1A1, 2E1, and 3A4 in squamous epithelium from African-American and Caucasian pediatric patients. The third aim was to compare the expression of CYPs 1A1, 2E1, 3A4, and GST-pi on the p16 expression in patients with SCCHN. EXPERIMENTAL DESIGN: The expression of CYP 1A1, 2E1, 3A4, GST-pi, and p16 was quantified by immunoblotting. Expression of CYPs 1A1, 2E1, and 3A4 was quantified in tissue from 160 pediatric patients undergoing tonsillectomy. Expression of CYPs 1A1, 2E1, 3A4, GST-pi, and p16 was determined in 46 resected SCCHN patients. RESULTS: Large interindividual variability in the expression of these enzymes was observed in the pediatric and adult populations. No significant difference was observed in CYP 1A1, 2E1, and 3A4 expression of Caucasian and African-American patients. There was no correlation between p16 and enzyme expression in patients with SCCHN. CONCLUSION: Evaluation of CYP expression in the target tissue of interest is feasible. The clinical significance of CYPs and GST-pi alterations in the risk of developing SCCHN will need to be investigated in larger trials.

Blotting, Western↗

PubMed2004

Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck.

BACKGROUND: Despite the use of resection and postoperative radiotherapy, high-risk squamous-cell carcinoma of the head and neck frequently recurs in the original tumor bed. We tested the hypothesis that concurrent postoperative administration of cisplatin and radiotherapy would improve the rate of local and regional control. METHODS: Between September 9, 1995, and April 28, 2000, 459 patients were enrolled. After undergoing total resection of all visible and palpable disease, 231 patients were randomly assigned to receive radiotherapy alone (60 to 66 Gy in 30 to 33 fractions over a period of 6 to 6.6 weeks) and 228 patients to receive the identical treatment plus concurrent cisplatin (100 mg per square meter of body-surface area intravenously on days 1, 22, and 43). RESULTS: After a median follow-up of 45.9 months, the rate of local and regional control was significantly higher in the combined-therapy group than in the group given radiotherapy alone (hazard ratio for local or regional recurrence, 0.61; 95 percent confidence interval, 0.41 to 0.91; P=0.01). The estimated two-year rate of local and regional control was 82 percent in the combined-therapy group, as compared with 72 percent in the radiotherapy group. Disease-free survival was significantly longer in the combined-therapy group than in the radiotherapy group (hazard ratio for disease or death, 0.78; 95 percent confidence interval, 0.61 to 0.99; P=0.04), but overall survival was not (hazard ratio for death, 0.84; 95 percent confidence interval, 0.65 to 1.09; P=0.19). The incidence of acute adverse effects of grade 3 or greater was 34 percent in the radiotherapy group and 77 percent in the combined-therapy group (P<0.001). Four patients who received combined therapy died as a direct result of the treatment. CONCLUSIONS: Among high-risk patients with resected head and neck cancer, concurrent postoperative chemotherapy and radiotherapy significantly improve the rates of local and regional control and disease-free survival. However, the combined treatment is associated with a substantial increase in adverse effects.

Adolescent↗

PubMed2004

Detection of plasminogen activators in oral cancer by laser capture microdissection combined with zymography.

Plasminogen activation is believed to be critical to the progression of oral squamous cell carcinoma by facilitating matrix degradation during invasion and metastasis, and high levels of urokinase plasminogen activator (uPA) and plasminogen activator (PA) inhibitor-1 (PAI-1) in tumors predict poor disease outcome. We describe the development of a novel method for studying PA in oral cancer that combines the sensitivity and specificity of zymography with the spatial resolution of immunohistochemistry. Laser capture microdissection (LCM) was combined with plasminogen-casein zymography to analyze uPA, tissue PA (tPA), uPA-PAI-1 complexes, and tPA-PAI-1 complexes in 11 tumors and adjacent non-malignant epithelium from squamous cell carcinomas of the tongue, floor of mouth, larynx, and vocal cord. uPA was detectable in all tumor samples analyzed, uPA-PAI-1 complexes in three samples, and tPA in nine. PA was detectable in as little as 0.5 microg protein lysate from microdissected tumors. In all specimens, uPA expression was highly increased in tumor tissue compared to adjacent non-malignant tissue. In conclusion, LCM combined with zymography may be excellently suited for analyzing the prognostic significance and causal involvement of the plasminogen activation system in oral cancer.

Aged↗

PubMed2004

Correlation of histopathological variants, cellular DNA content, and clinical outcome in adenoid cystic carcinoma of the salivary glands.

OBJECTIVE: To study the correlation between flow cytometrically measured DNA ploidy with prognostically important histopathologic groups and clinical outcome in patients with adenoid cystic carcinoma of the salivary glands. STUDY DESIGN: 46 tumor specimens were analyzed flow cytometrically for DNA content and assessed for histological grade. Correlations were made between tumor DNA ploidy and histopathological grade, and disease-free and overall survival of these patients. RESULTS: Of the 46 patients, 31 had a cribiform/tubular histologic pattern, and 15 had a solid pattern. 84% of the tumors with cribriform/tubular pattern were DNA diploid, compared with 33% of tumors that were graded solid. This difference proved to be statistically significant (chi(2)11.75, P = 0.0006). Overall and disease-free survival periods were longer for patients with DNA diploid tumors in both groups, 63% vs. 36% and 62% vs 38%, respectively. CONCLUSIONS: Tumor DNA ploidy correlates with prognostically important tumor histopathology as well as overall and disease-free survival in patients with adenoid cystic carcinoma of the salivary gland. EBM RATING: B-3.

Adult↗

PubMed2004

Pseudoaneuploid subpopulations detected in normal upper aerodigestive tract mucosa consistent with physiological apoptosis in normally differentiating squamous mucosa.

OBJECTIVES: While evaluating the validity of using normal human mucosal cells from the upper aerodigestive tract as diploid standards for DNA content studies of squamous cell cancer of head and neck by flow cytometry, pseudoaneuploidy was frequently detected. The purpose of this study was to further evaluate these DNA content abnormalities encountered in normal human mucosal cells and correlate them to physiological apoptosis. STUDY DESIGN: Thirty-two specimens of upper areodigestive tract mucosa from 18 surgical resections, 11 fresh autopsies, and 3 buccal scrapings were examined for DNA content by flow cytometry. RESULTS: Pseudoaneuploidy, which ranged from sub-G0/G1 peaks to hyperdiploid peaks with increased 90 degrees light scattering properties was found in 60% of these specimens. Fluorescent microscopic examination of the sorted DNA pseudoaneuploid cells demonstrated cells undergoing apoptosis. CONCLUSION: This unexpected pseudoaneuploidy in normal mucosal cells was a result of physiological apoptosis, a normal component of squamous differentiation. EBM RATING: B-2.

Aneuploidy↗

PubMed2004

Microsatellite alterations in african americans with head and neck cancer.

OBJECTIVE: To determine the genetic differences between African Americans (AA) and Non-African Americans (NAA) with head and neck squamous cell carcinoma (HNSCC). METHODS: DNA was obtained from tumor tissues and peripheral blood from 18 AA and 19 NAA patients with HNSCC. Microsatellite analysis using a fluorescent technique was performed on chromosomal arms 1p, 3p, 4q, 9p, 13q, and 17p. Statistical analyses were performed on the molecular and clinical outcome data. RESULTS: Based on the Surveillance, Epidemiologic, and End Result (SEER) data from southeast Michigan, the incidence rate of HNSCC in AA has been higher than for NAA, and the overall 5-year relative survival rate is lower for AA than NAA (36.2% vs. 47.6%). In this study, we found that the rate of loss of heterozygosity of chromosomal arms 1p, 3p, 4q, 9p, 13q, and 17p ranged from 68.8% to 83.3% for HNSCC in AA and from 66.7% to 90.0% in NAA. The difference in the rates of microsatellite alterations in chromosomal arms 3p, 4q, and 9p between AA and NAA were between 12.5% and 20% and were not statistically significant. CONCLUSION: The incidence and clinical outcomes for AA with HNSCC are different from that of NAA in southeast Michigan. In our group of patients with HNSCC, differences in rates of microsatellite alterations and survival were found between AA and NAA; however, these differences were not statistically significant. We conclude that genetic difference, as determined by the rates of microsatellite alterations, is not predictive of outcome difference between AA and NAA HNSCC patients.

Adult↗

PubMed2004

Enhancement of Ad-p53 therapy with docetaxel in head and neck cancer.

OBJECTIVE: The objective of this project was to determine the mechanisms in which docetaxel enhances Ad-p53 tumor suppressive effects in head and neck cancer. BACKGROUND: In advanced head and neck squamous cell carcinoma (HNSCC), the 5-year survival rate is less than 40%. Because patients with advanced HNSCC have a high rate of local-regional failure (40-60%) with existing treatment modalities, aggressive local therapy approaches need to be developed. Previous data show that docetaxel or Ad-p53 alone have significant anti-tumor activity in HNSCC. Before testing whether a combination approach (Ad-p53 and docetaxel) could be developed in clinical trials, preclinical experiments were performed. METHODS: The p53 gene was overexpressed in 2 head and neck squamous carcinoma (HNSCC) cell lines, HN30 and HN12, and a murine Balb/c mucoepidermoid carcinoma (BMEC) cell line. Docetaxel's enhancement of adenoviral transduction (bGAL expression), coxsakie-adenovirus receptor (CAR) expression, and Ad-p53 induction of apoptosis (Annexin V expression) were measured. The modulation of regulators in the cell cycle, apoptosis and signal transduction pathways were measured using Western blot. RESULTS: Docetaxel increased adenoviral transduction, which was dependent on the dose of docetaxel and levels of Ad-bGAL. The enhanced viral transduction was due in part to the upregulation of the CAR protein. Pretreatment with docetaxel enhanced Ad-p53-induced apoptosis through increased expression of exogenous p53. Together, the combination of docetaxel and Ad-p53 altered expression of key regulators in the cell cycle, apoptosis and signal transduction pathways with an increase in the expression of p53, bax, cleaved PARP, cleaved caspase-3 and phosphorylation of c-Jun at position at Ser. Cyclin A and B1 expression were down regulated by docetaxel and Ad-p53. When comparing the docetaxel-resistant to sensitive cell lines, the altered expression of p27 and skp1 by docetaxel and Ad-p53 were dissimilar between these cell lines. CONCLUSIONS: Docetaxel enhanced Ad-p53 transduction and increased expression of exogenous p53 gene transfer, apoptosis, and antitumor mechanisms. These results support a clinical combination of docetaxel with p53 gene therapy in patients with head and neck cancer.

Animals↗

PubMed2003

An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer.

PURPOSE: The Head and Neck Intergroup conducted a phase III randomized trial to test the benefit of adding chemotherapy to radiation in patients with unresectable squamous cell head and neck cancer. PATIENTS AND METHODS: Eligible patients were randomly assigned between arm A (the control), single daily fractionated radiation (70 Gy at 2 Gy/d); arm B, identical radiation therapy with concurrent bolus cisplatin, given on days 1, 22, and 43; and arm C, a split course of single daily fractionated radiation and three cycles of concurrent infusional fluorouracil and bolus cisplatin chemotherapy, 30 Gy given with the first cycle and 30 to 40 Gy given with the third cycle. Surgical resection was encouraged if possible after the second chemotherapy cycle on arm C and, if necessary, as salvage therapy on all three treatment arms. Survival data were compared between each experimental arm and the control arm using a one-sided log-rank test. RESULTS: Between 1992 and 1999, 295 patients were entered on this trial. This did not meet the accrual goal of 362 patients and resulted in premature study closure. Grade 3 or worse toxicity occurred in 52% of patients enrolled in arm A, compared with 89% enrolled in arm B (P <.0001) and 77% enrolled in arm C (P <.001). With a median follow-up of 41 months, the 3-year projected overall survival for patients enrolled in arm A is 23%, compared with 37% for arm B (P =.014) and 27% for arm C (P = not significant). CONCLUSION: The addition of concurrent high-dose, single-agent cisplatin to conventional single daily fractionated radiation significantly improves survival, although it also increases toxicity. The loss of efficacy resulting from split-course radiation was not offset by either multiagent chemotherapy or the possibility of midcourse surgery.

Adult↗

PubMed2003

Hormone-refractory prostate cancer responding to capecitabine.

A 66-year-old male patient with advanced prostate cancer presented with bony metastases, including pathologic fractures and hepatosplenomegaly. The patient responded to luteinizing hormone-releasing hormone agonists for more than 1 year. A clear progression while taking luteinizing hormone-releasing hormone agonists manifested as a progressive rise in prostate-specific antigen, alkaline phosphatase, hepatosplenomegaly, and myelophthisic pancytopenia. We administered capecitabine for 5 months with a complete clinical response. At last follow-up, the patient's liver function tests and prostate-specific antigen level have normalized. Liver size by computed tomography and blood counts both improved. To our knowledge, no previous case reports of capecitabine in the treatment of prostate cancer have been published.

Adenocarcinoma↗