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Arlene A Forastiere

Publications and source records attributed to Arlene A Forastiere.

27 records · Page 2Linked to original sources
PubMed2003

Prognostic importance of promoter hypermethylation of multiple genes in esophageal adenocarcinoma.

PURPOSE: We investigated aberrant methylation patterns in esophageal adenocarcinoma and correlated the findings to patient survival and tumor recurrence. EXPERIMENTAL DESIGN: Gene promoter methylation was performed in 82 samples from 41 esophagectomy patients consisting of 41 adenocarcinoma samples, each with its adjacent nonmalignant tissue, which included one sample with Barretts metaplasia. The methylation status of seven genes was determined. Epigenetic silencing was confirmed using immunohistochemical staining. Kaplan-Meier plots were constructed using disease-specific survival as the primary end point and the interval from surgery to tumor recurrence as the secondary end point. The association of clinicopathological and biomolecular risk factors to survival and recurrence was performed using the Log-rank test and Cox proportional hazards model for multivariate analysis. RESULTS: Methylation frequencies of the genes analyzed were APC, 68%; E-cadherin, 66%; O(6)-methylguanine DNA methyltransferase, 56%; ER, 51%; p16, 39%; DAP-kinase, 19%; and TIMP3, 19%. DNA methylation of some genes individually showed only trends toward diminished survival, whereas patients whose tumors had >50% of their gene profile methylated had both significantly poorer survival (P = 0.04) and earlier tumor recurrence (P = 0.05) than those without positive methylation. By multivariate analysis, the hazard ratios (HRs) with positive methylation status were more powerful predictors of survival [HR 2.7 (1.14-6.45; 95% confidence interval)] and tumor recurrence [HR 2.5 (1.11-5.6)] than age (HR 2.03 and 1.96, respectively) or stage (HR 1.48 and 1.67, respectively). CONCLUSIONS: Our data suggest that positive methylation status for multiple genes in esophageal adenocarcinoma is a predictor of poor prognosis.

Adenocarcinoma↗
PubMed2003

Mature survival results with preoperative cisplatin, protracted infusion 5-fluorouracil, and 44-Gy radiotherapy for esophageal cancer.

PURPOSE: To assess the long-term survival results after cisplatin, protracted infusion 5-fluorouracil, and concurrent radiotherapy (RT) followed by surgical resection of esophageal cancer. METHODS AND MATERIALS: Ninety-two patients with esophageal cancer (65 with adenocarcinoma and 27 with squamous cell carcinoma) were treated in two sequential protocols of preoperative chemoradiotherapy. The patients had tumor confined to the esophagus and regional nodes, including celiac nodes for middle and distal lesions. In trial A (1989-1994), 50 patients were treated with 44 Gy RT (2 Gy/d) along with concurrent 5-fluorouracil 300 mg/m(2)/d given by protracted venous infusion on Days 1-30 and cisplatin 26 mg/m(2) on Days 1-5 and 26-30. In trial B (1995-1997, 42 patients), the chemotherapy dosages during RT were reduced to 5-fluorouracil 225 mg/m(2)/d protracted venous infusion and cisplatin 20 mg/m(2)/d on Days 1-5 and 16-30; three cycles of paclitaxel 135 mg/m(2)and cisplatin 75 mg/m(2) were given postoperatively. Surgery generally occurred 4-6 weeks after completion of the planned preoperative therapy. Transhiatal resection was performed whenever possible. RESULTS: Of the 92 patients, 86 (93%) underwent surgery (1 refused, 2 died preoperatively, and 3 developed evidence of metastatic disease). Of the 92 patients, 80 (87%) had complete resections with negative margins (3 had positive margins and 3 had distant metastases discovered at surgery). The pathologic complete response rate was 33% (30 of 92). The median follow-up was 63.5 months. The median survival and disease-specific survival for all enrolled patients was 35 and 59 months, respectively. The 5-year survival and disease-specific survival rate was 40% and 49%, respectively. Patients with a pathologic complete response had a 67% survival rate at 5 years (median not reached), and the remainder of patients had a 5-year survival rate of 27% (median 21 months; p <0.001). For 21 patients alive after 5 years (60-121 months), 2 died of their disease and all others were disease free. Eight patients with pathologic Stage I tumor at the time of surgery had survival similar to those with a complete response to preoperative therapy. The median survival for patients with pathologic Stage IIA, IIB, III, and IV disease at the time of surgery was 22, 13.5, 18, and 4.9 months, respectively. The pattern of initial failure was local/regional alone in 6% (5 of 90), local/regional plus distant in 3% (3 of 90), and distant alone in 47% (42 of 90). No differences were noted in survival or response rate between those with adenocarcinoma or squamous cell carcinoma. CONCLUSION: The promising 5-year survival results and low rate of late cancer-related deaths suggest that these regimens of intensive neoadjuvant therapy may improve the overall cure rate. The pathologic stage after neoadjuvant therapy is an important predictor of survival and may be useful in selecting patients for novel adjuvant therapies. Isolated local failure is uncommon, indicating that efforts to improve the therapeutic outcome should focus on optimizing systemic therapy rather than intensifying the RT. Additional randomized data are needed to assess the benefits of this therapeutic approach fully.

Adenocarcinoma↗
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↗
PubMed2002

Phase II Trial of docetaxel and cisplatin combination chemotherapy in patients with squamous cell carcinoma of the head and neck.

PURPOSE: To assess the antitumor activity and toxicity of docetaxel plus cisplatin chemotherapy in patients with recurrent or incurable squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Patients with recurrent or incurable SCCHN were eligible if they were chemotherapy naive or if they had received one prior regimen as neoadjuvant or concurrent treatment with radiation. Patients who had received chemotherapy for recurrence or prior taxanes were ineligible. Patients received docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) on day 1; cycles were repeated every 21 days. RESULTS: Toxic effects and length of survival were assessable in 36 patients and tumor response was assessable in 32, for whom the overall response rate was 40% (13 of 32) (6% complete response and 34% partial response). Median time to response was 5 weeks, and median duration was 4.9 months. In the intent to treat population (n = 36), median time to disease progression was 4 months. Median survival (n = 36) was 9.6 months, and the 12-month survival rate was 27%. Grade 4 neutropenia was observed in 71% of patients. Two patients (6%) experienced serious fever during grade 4 neutropenia (without documented infection) that required intravenous antibiotics, and an additional four patients had grade 3 infection. Other severe (grades 3 and 4) toxic effects were asthenia (25%), nausea (11%), fever (8%), vomiting (8%), severe hypersensitivity reactions (8%), and diarrhea (8%). Severe stomatitis (grade 3) occurred in only one patient. CONCLUSION: Docetaxel plus cisplatin is an effective regimen with an acceptable safety profile for palliation of recurrent SCCHN. Relative to the standard regimen of cisplatin/fluorouracil, this regimen may offer higher tumor response and survival rates with short outpatient administration and a lower incidence of severe mucosal toxicity.

Adult↗
PubMed2002

Phase II and biologic study of interferon alfa, retinoic acid, and cisplatin in advanced squamous skin cancer.

PURPOSE: The purpose of this study was to test interferon alfa (IFNalpha), 13-cis-retinoic acid (13cRA), and cisplatin biochemotherapy in advanced squamous cell carcinoma (SCC) of the skin. PATIENTS AND METHODS: Patients with advanced skin SCC received IFNalpha (5 x 10(6) IU/m(2), subcutaneous injection, three times a week), 13cRA (1 mg/kg, orally, daily), and cisplatin (20 mg/m(2), intravenous injection, weekly) in a phase II trial. The growth inhibition, cell-cycle, and apoptosis activity of these agents was evaluated in two skin SCC cell lines (SRB1-m7 and SRB12-p9). RESULTS: Thirty-nine patients were enrolled. All were assessable for survival, 35 for response and toxicity (median follow-up was 38 months). The overall and complete response rates were 34% and 17%, respectively, with median durations of 9 and 35.4 months, respectively. The response rate was higher in locally advanced (67%) than metastatic (17%) disease (P =.007). Median survival was 14.6 months. One-, 2-, and 5-year survival rate estimates were 58%, 32%, and 21%, respectively. Toxicity included generally mild to moderate fatigue and mucocutaneous dryness, moderate to severe neutropenia (38%), and neutropenic fever (6%). There were no treatment-related deaths. In vitro growth inhibition and apoptosis effects of cisplatin were differential and inversely associated with those of retinoic acid and especially IFNalpha in two skin SCC lines. CONCLUSION: The rising incidence, morbidity, and mortality of advanced skin SCC are a major challenge for clinical oncologists. Combined 13cRA, IFNalpha, and cisplatin was clinically active in extensive locally advanced disease. Each agent had independent, non-cross-resistant biologic effects in vitro, which may account for the combination's clinical activity.

Adult↗
PubMed2002

Postesophagectomy morbidity, mortality, and length of hospital stay after preoperative chemoradiation therapy.

BACKGROUND: Data suggest that preoperative chemoradiation improves survival in patients with stage II and III esophageal tumors. Whether preoperative therapy increases postesophagectomy morbidity and mortality has not been determined. This study evaluates our postoperative results after chemoradiation therapy. METHODS: From 1989 through 1998, 120 consecutive patients underwent chemoradiation therapy followed by esophagectomy at our institution. The medical records for these patients were reviewed to determine patient age, sex, race, cell type, operative technique, complications, deaths, and length of hospital stay (LOS). RESULTS: There were 106 (88%) men and 14 (12%) women with a mean age of 58 (32 to 77) years. White patients predominated (114 of 120, 95%); 98 (82%) had adenocarcinoma and 22 (18%) had squamous cell carcinoma. Operative technique was transhiatal in 91 (76%) patients, three-incision in 23 (19%), Ivor-Lewis in 4 (3%), and thoracoabdominal in 2 (2%). There was 1 death. Complications developed in 44 (37%) patients; 59% (13 of 22) of squamous cell carcinoma patients and 32% (31 of 98) of adenocarcinoma patients developed complications. Respiratory complications occurred in 32% (7 of 22) of squamous cell carcinoma patients and in 3% (3 of 98) of adenocarcinoma patients. Mean length of stay after surgery was 15 days (range 7 to 163). CONCLUSIONS: Postesophagectomy results after chemoradiation therapy are comparable to those reported after esophagectomy alone. Squamous cell carcinoma patients are nearly twice as likely to develop postoperative complications and are more likely to have respiratory complications than adenocarcinoma patients.

Adenocarcinoma↗
PubMed2002

Organ preservation trials for laryngeal cancer.

Organ-preservation strategies include definitive radiation therapy alone, induction chemotherapy followed by radiotherapy, and concurrent chemoradiotherapy. Over the past decade, induction chemotherapy followed by radiotherapy has been the standard for the nonsurgical management of advanced laryngeal cancer. Over this same period, however, other nonsurgical strategies have been under evaluation. These approaches include radiotherapy with concurrent chemotherapy to take advantage of the radiosensitizing properties of most cytotoxic drugs with activity against squamous cell cancer, altered fractionation radiotherapy, and the incorporation of molecularly targeted therapeutics into multimodality treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Phase II trial of docetaxel chemotherapy in patients with incurable adenocarcinoma of the esophagus.

BACKGROUND: Chemotherapy remains the primary mode of treatment for metastatic carcinoma of the esophagus. The efficacy of various chemotherapeutic regimens has been studied predominantly in patients with squamous cell carcinoma of the esophagus. In light of the increasing incidence of adenocarcinoma of the esophagus, studies evaluating newer chemotherapy agents, such as docetaxel, in this patient population are necessary. The objective of this trial was to determine the complete and partial response rate of docetaxel in patients with incurable adenocarcinoma of the esophagus. PATIENTS AND METHODS: Eligible patients had histologically confirmed metastatic adenocarcinoma of the esophagus or locally extensive disease not curable with surgery or radiation therapy. Patients were either chemotherapy naive or previously treated with chemotherapy (including paclitaxel). Docetaxel was administered at a dose of 75 mg/m2 every three weeks intravenously. Appropriate imaging studies/examinations were obtained after every two cycles to evaluate response. RESULTS: A total of 22 patients were enrolled in the trial. Chemotherapy-naive patients achieved a response rate of 18% (95% CI = 2.3 to 51.8) while patients who received prior chemotherapy achieved a 0% response rate (95% CI = 0 to 25). There were no complete responses. The overall median survival time is 3.4 months and the one-year survival rate is 21%. The toxicities included febrile neutropenia (32%) as well as grade 3 and 4 fatigue (14%) and anorexia (9%). CONCLUSIONS: Although chemotherapy naive patients achieved an 18% response rate and no responses were seen in previously treated patients, the limitations of this trial does not allow for any definitive conclusions to be made about the efficacy of single agent docetaxel chemotherapy in patients with incurable esophageal cancer.

Adenocarcinoma↗