PubMed Health⌕ Search

Biomedical subjects

A A Forastiere

Publications and source records attributed to A A Forastiere.

At least 19 recordsLinked to original sources
PubMed2001

Phase III comparison of high-dose paclitaxel + cisplatin + granulocyte colony-stimulating factor versus low-dose paclitaxel + cisplatin in advanced head and neck cancer: Eastern Cooperative Oncology Group Study E1393.

PURPOSE: To determine dose-response effects and the activity of paclitaxel combined with cisplatin in patients with incurable squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: Two hundred ten patients with locally advanced, recurrent, or metastatic disease were randomly placed in either Arm A, paclitaxel 200 mg/m(2) (24-hour infusion) + cisplatin 75mg/m(2) + granulocyte colony-stimulating factor, or Arm B, paclitaxel 135 mg/m(2) (24-hour infusion) + cisplatin 75 mg/m(2). Cycles were repeated every 3 weeks until progression or a total of 12 cycles for complete responses. Primary outcomes were event-free and overall survival. RESULTS: No significant differences in outcomes were observed between the high- and low-dose paclitaxel regimens. The estimated median survival was 7.3 months (95% confidence interval, 6.0 to 8.6). The 1-year survival rate was 29%, and event-free survival was 4.0 months. The objective response rate (complete response plus partial response) was 35% for the high-dose patients and 36% for the low-dose patients. Myelosuppression was the most frequent toxicity: grade 3 or 4 granulocytopenia, 70% of patients in Arm A and 78% in Arm B; febrile neutropenia, 27% of patients in Arm A and 39% in Arm B. Grade 5 toxicities occurred in 22 patients (10.5%). Treatment was terminated early in 31% because of excessive toxicity or patient refusal. CONCLUSION: This phase III multicenter trial showed (1) no advantage for high-dose paclitaxel and (2) excessive hematologic toxicity associated with both regimens. Therefore, neither of the paclitaxel regimens evaluated in this trial can be recommended.

Adult↗
PubMed2001

Frequent hypermethylation of the 5' CpG island of E-cadherin in esophageal adenocarcinoma.

PURPOSE: E-cadherin, a M(r) 120,000 transmembrane glycoprotein, mediates calcium-dependent intercellular adhesion that is essential for normal tissue homeostasis. Loss of E-cadherin occurs in a variety of epithelial tumors and is correlated with invasion and metastasis. In esophageal adenocarcinoma, reduction of E-cadherin expression has been demonstrated previously, but mutations of the gene (CDH1) are rare. EXPERIMENTAL DESIGN: In this study, we used a nested PCR approach to examine the methylation status of the 5' CpG island of E-cadherin in esophageal specimens obtained from individuals with and without a history of esophageal cancer. RESULTS: In four individuals without esophageal cancer, E-cadherin was completely unmethylated in normal squamous cell-lined esophageal mucosa. In contrast, in patients with esophageal adenocarcinoma, E-cadherin was methylated in 26 of 31 (84%) tumor specimens. In the majority of cases, matched normal tissue (esophagus or stomach) from each patient was completely unmethylated. By immunostaining, methylated tumor samples demonstrated heterogeneously decreased membranous E-cadherin staining. CONCLUSIONS: These data suggest that epigenetic silencing via aberrant methylation of the E-cadherin promoter is a common cause of inactivation of this gene in esophageal adenocarcinoma.

Adenocarcinoma↗
PubMed2000

Neoadjuvant chemoradiation followed by surgery for resectable esophageal cancer.

Neoadjuvant chemoradiation (NAC) therapy protocols were developed to improve survival in patients with resectable esophageal cancer. Our experience with two consecutive NAC therapy trials is reviewed. Both studies included patients with localized squamous cell cancer and adenocarcinoma. Patients were treated with cisplatinum 26 mg/m2/day (days 1-5 and 26-30), 5-Fluorouracil (5-FU) 300 mg/m2/day (days 1-30), concurrent radiotherapy (4400 cGy) followed by esophagectomy. In the second trial, adjuvant taxol was added. The first protocol had 50 patients. Two patients died, both before surgery, one from sepsis. There was no residual viable tumor (CR) in 19 (40%) patients. The median survival time was 31 months. The 5-year survival rate of 36% compared favorably with concurrent 5-year survival of 18% for surgery alone. Forty-one patients were enrolled in the second trial. All underwent surgery. There were no treatment or operative deaths. Survival data for this group is maturing. Combined results from both protocols are: treatment mortality of 2.2%, complete response rate of 37%, and a median and 3-year disease-specific survival of 42 months and 54%, respectively. We conclude that NAC followed by surgery improves survival over surgery alone and that CR is predictive of improved survival.

Adenocarcinoma↗
PubMed2000

The role of laparoscopy in preoperative staging of esophageal cancer.

BACKGROUND: Diagnostic laparoscopy has been used to determine resectability and to prevent unnecessary laparotomy in patients with advanced esophageal cancer. The objective of this prospective study was to evaluate the role of laparoscopy in conjunction with computed tomography (CT) scan in staging patients with esophageal cancer. METHODS: From March 1995 to October 1998, 59 patients with biopsy-proven esophageal cancer underwent diagnostic laparoscopy with concurrent vascular access device and feeding jejunostomy tube placement. RESULTS: Laparoscopy changed the treatment plan in 10 of 59 patients (17%). Of the patients with normal-appearing regional or celiac nodes, 78% were confirmed by biopsy to be tumor free, whereas 76% of patients with abnormal-appearing nodes were confirmed by biopsy to have node-positive disease. CONCLUSIONS: Diagnostic laparoscopy is useful for detecting and confirming nodal involvement and distant metastatic disease that potentially would alter treatment and prognosis in patients with esophageal cancer.

Adult↗
PubMed2000

Mutations in beta-catenin and APC genes are uncommon in esophageal and esophagogastric junction adenocarcinomas.

Beta-catenin plays important roles in both intercellular adhesion and signal transduction. Mutations in the beta-catenin or adenomatous polyposis coli (APC) gene can alter the degradation of beta-catenin and cause aberrant accumulation of beta-catenin result in increased transcription of target genes. The dysregulated APC/beta-catenin pathway has been recently discovered as an important mechanism of tumorigenesis in various cancers, but its role in esophageal adenocarcinomas is not clear. Therefore, we studied the beta-catenin gene mutation, allelic loss of chromosome 5q, and APC gene mutation in esophageal and esophagogastric junction adenocarcinomas. Two (2%) somatic mutations in exon 3 of the beta-catenin gene, encompassing the region for glycogen synthase kinase-3beta phosphorylation, were detected from 109 adenocarcinomas. Chromosomal allelic loss on 5q was frequent in 45.3% (44/97) of tumors. Only one missense mutation in the mutation cluster region of the APC gene was detected from 38 esophageal and esophagogastric junction adenocarcinomas with the 5q allelic loss. Our results based on partial screening mutational analyses indicate that mutations of APC/beta-catenin pathway, unlike in colorectal carcinoma, involve only a small subset of esophageal and esophagogastric junction adenocarcinoma.

Adenocarcinoma↗
PubMed2000

Phase II evaluation of preoperative chemoradiation and postoperative adjuvant chemotherapy for squamous cell and adenocarcinoma of the esophagus.

PURPOSE: This phase II trial evaluated continuous-infusion cisplatin and fluorouracil (5-FU) with radiotherapy followed by esophagectomy. The objectives of this trial were to determine the complete pathologic response rate, survival rate, toxicity, pattern of failure, and feasibility of administering adjuvant chemotherapy in patients with resectable cancer of the esophagus treated with preoperative chemoradiation. PATIENTS AND METHODS: Patients were staged using computed tomography, endoscopic ultrasound, and laparoscopy. The preoperative treatment plan consisted of continuous intravenous infusion of cisplatin and 5-FU and a total dose of 44 Gy of radiation. Esophagogastrectomy was planned for approximately 4 weeks after the completion of chemoradiotherapy. Paclitaxel and cisplatin were administered as postoperative adjuvant therapy. RESULTS: Forty-two patients were enrolled onto the trial. Of the 39 patients who proceeded to surgery, 29 responded to preoperative treatment: 11 achieved pathologic complete response (CR) and 18 achieved a lower posttreatment stage. Five patients had no change in stage, whereas eight had progressive disease (four with distant metastases and four with increases in the T and N stages). At a median follow-up of 30.2 months, the median survival time has not been reached and the 2-year survival rate is 62%. The median survival of pathologic complete responders has not been reached, whereas the 2-year survival rate of this group is 91% compared with 51% in patients with complete tumor resection with residual tumor (P =.03). CONCLUSION: An excellent survival rate, comparable to that of our prior preoperative trial, was achieved with lower doses of preoperative cisplatin and 5-FU concurrent with radiotherapy.

Adenocarcinoma↗
PubMed2000

Adenocarcinoma of the esophagus: risk factors and prevention.

Esophageal cancer, with an estimated number of 12,300 new cases in the year 2000, is relatively uncommon in the United States but produces a high number of annual deaths, estimated at 12,100. Moreover, the incidence of the adenocarcinoma histologic type of esophageal cancer has been rising over the past two decades. Identification of risk factors could lead to primary prevention, as well as earlier diagnosis, treatment, and increased survival. Multiple risk factors are associated with the development of esophageal adenocarcinoma. These include Barrett's esophagus, acid peptic disorders, motor disorders of the esophagus, other malignancies, medications, environmental exposures, diet, and nutrition. However, no one particular risk factor is responsible for the rising incidence of esophageal cancer. Several preventive strategies are under investigation using such agents as nonsteroidal anti-inflammatory drugs (NSAIDs), selenium, alpha-difluoromethylornithine (DFMO), and retinoids. As we gain more insight into the biology of this disease, other risk factors will hopefully be identified that will enable us to develop effective prevention strategies and, thus, reverse the current rising incidence of esophageal carcinoma.

Adenocarcinoma↗
PubMed1999

Larynx preservation in head and neck cancers. A discussion of the National Comprehensive Cancer Network Practice Guidelines.

The management of advanced cancers of the larynx and hypopharynx has become increasingly complex as different treatment modalities, including surgery, radiation, and chemotherapy, have been combined with the goal of improving local disease control and disease-specific survival. A union of 17 comprehensive cancer centers in the United States, the National Comprehensive Care Network (NCCN), was formed in 1995 to promote state-of-the-art cancer care. To achieve this goal, multidisciplinary panels of experts from member institutions have created disease-specific practice guidelines for the evaluation and treatment of cancer patients, including those with head and neck cancers. Although detailed analysis of surgical methods and radiation techniques are beyond the scope of this article, the evolving laryngeal preservation strategies for patients with advanced, resectable hypopharyngeal or laryngeal (including supraglottic and glottic) cancers are reviewed using relevant sections of the NCCN practice guidelines as a framework for discussion.

Antineoplastic Agents↗
PubMed1999

Multimodality therapy of patients with locally advanced squamous cell cancer of the head and neck: preliminary results of two pilot trials using paclitaxel and cisplatin.

Chemotherapy has been integrated into the initial treatment of patients with locally advanced squamous cell cancer of the head and neck to improve locoregional control and survival. Two strategies for improving these outcomes are the use of new, potentially more effective drugs either with concurrent radiotherapy or as induction regimens. Because of its inherent activity against squamous cell cancer of the head and neck and its radiation-sensitizing properties, paclitaxel may be a valuable agent in the treatment of this patient population. We describe the preliminary results of two trials that evaluated the combination of paclitaxel and cisplatin in patients with locally advanced disease: a phase I trial of weekly paclitaxel and cisplatin with concurrent postoperative radiation therapy in patients with high-risk disease and a phase I/II trial of paclitaxel as a 96-hour infusion in combination with cisplatin as induction therapy. These studies identified tolerable doses of paclitaxel and cisplatin administered in these settings, with apparent clinical activity. These trials formed the basis for subsequent evaluation of induction paclitaxel and cisplatin followed by definitive radiotherapy and concurrent weekly paclitaxel and cisplatin plus radiotherapy.

Adult↗
PubMed1999

Prognostic value of p53, glutathione S-transferase pi, and thymidylate synthase for neoadjuvant cisplatin-based chemotherapy in head and neck cancer.

Neoadjuvant cisplatin-based chemotherapy has been widely used in the last decade for organ preservation or unresectable disease in advanced stage head and neck cancer. We examined the expression of a series of tumor markers that have been associated with chemotherapy resistance in pretreatment biopsies from 68 patients who received cisplatin-based neoadjuvant chemotherapy at either of two institutions. Patients received either cisplatin/5-fluorouracil (n = 49) or cisplatin/paclitaxel (n = 19). Expression of p53, glutathione S-transferase pi (GSTpi), thymidylate synthase (TS), c-erbB2, and multidrug resistance-associated protein was examined by immunohistochemistry. Expression of glutathione synthetase mRNA was measured by in situ hybridization. The overall response rate for cisplatin-based neoadjuvant treatment was 79%. The expression of several of the tumor markers was associated with resistance to neoadjuvant treatment, but none reached statistical significance. Overall survival (OS) was strongly correlated with the absence of p53 expression. The OS at 3 years was 81% in the p53-negative group, whereas it was 30% in the p53-positive group for patients treated with neoadjuvant chemotherapy (P < 0.0001). Expression of GST pi and TS was also significantly correlated with decreased OS after neoadjuvant treatment. At 3 years, the OS rate was 82% in the low GSTpi score group, compared to 46% in the high GSTpi score group (P = 0.0018). In the TS-negative group, the 3-year OS rate was 71% compared with 40% in the TS-positive group (P = 0.0071). We conclude that p53, GSTpi, and TS may be clinically important predictors of survival in patients receiving neoadjuvant chemotherapy for head and neck cancer.

Adolescent↗
PubMed1999

Taxoids in head and neck cancer: the American approach.

The taxoids docetaxel and paclitaxel entered into clinical trials in the 1980s. Paclitaxel has dominated clinical investigations in the United States while docetaxel gained a foothold early in Europe. Now both agents are under intensive study in both countries. The Eastern Cooperative Oncology Group (ECOG) conducted a series of paclitaxel trials in patients with recurrent or metastatic squamous cell head and neck. The current study directly compares paclitaxel + cisplatin to cisplatin + 5-FU. Similarly, an international trial is in progress directly comparing docetaxel-based chemotherapy to cisplatin + 5-FU. For patients with locally advanced disease, phase I-II trials evaluating various doses and schedules of paclitaxel or docetaxel administered concurrently with radiotherapy are in progress or recently reported in preliminary form. No one regimen is clearly preferred. The results of selected studies and trials in progress in the United States are reviewed.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Induction and adjuvant chemotherapy for head and neck cancer: future perspectives.

Induction and adjuvant chemotherapy have been studied in combined modality trials over the last two decades. Induction chemotherapy as a strategy has failed to improve survival or local-regional control although some studies have reported a decrease in the rate of development of distant metastases. The role of induction chemotherapy is limited to preserving the larynx for patients with larynx or hypopharynx primaries. Trials of adjuvant chemotherapy or chemoradiation in resected patients suggest benefit for those with high risk features (multiple involved nodes, extracapsular extension, positive surgical margin). Definitive randomized studies are in progress in the United States and Europe. New targeted therapies will be investigated in future trials to improve survival.

Antineoplastic Agents↗
PubMed1998

Final report of a phase II evaluation of paclitaxel in patients with advanced squamous cell carcinoma of the head and neck: an Eastern Cooperative Oncology Group trial (PA390).

BACKGROUND: A number of single agents have been tested in patients with carcinoma of the head and neck receiving palliative treatment. In general, 15-30% of patients achieve a partial response lasting 3-4 months. Treatment has not been shown to alter survival rates. It is clear that new drugs with potentially greater activity need to be identified. For this purpose, the Eastern Cooperative Oncology Group conducted a Phase II evaluation of paclitaxel. METHODS: Patients with recurrent, metastatic, or locally advanced, incurable squamous cell carcinoma of the head and neck were eligible. The dose and schedule tested was the maximum tolerable dose of 250 mg/m2 determined from Phase I trials using a 24-hour infusion schedule and granulocyte-colony stimulating factor support. Courses were given at 3-week intervals until progression of disease was documented. Dose modifications were specified for hematologic toxicity and for neurotoxicity. RESULTS: Thirty-four patients were registered on study and 30 were eligible. Severe or life-threatening granulocytopenia was the most frequent toxicity observed, occurring in 91% of patients. Prior to response evaluation, one patient died of sepsis and one died of a myocardial infarct. Response was observed in 40% of eligible patients (4 complete and 8 partial responses). The median duration of response was 4.5 months (range, 2-20 months), with a median survival of 9.2 months and a 1-year survival rate of 33%. CONCLUSIONS: These results indicate that paclitaxel is an active agent for the treatment of squamous cell carcinoma of the head and neck. Studies evaluating alternative infusion schedules and combination regimens currently are underway.

Adult↗
PubMed1998

Squamous cell granulomas of the neck: histologic regression of metastatic squamous cell carcinoma following chemotherapy and/or radiotherapy.

BACKGROUND: For patients with squamous cell carcinoma of the head and neck (HNSCC), persistence of cervical adenopathy following organ-preservation therapy is a strong predictor of locoregional failure. Squamous cell granulomas of the neck may represent a regressed state of metastatic HNSCC; however, relevant clinicopathologic features of this lesion including its morphologic characteristics, association with therapy, and relationship to disease progression are not well defined. METHODS: We reviewed 866 consecutive neck dissections performed at The Johns Hopkins Hospital from 1984 to 1996. A total of eight cases showing a foreign-body giant-cell reaction to keratin in the absence of viable tumor formed the basis of this study. RESULTS: All eight cases were from patients with stage III or IV HNSCC with concurrent neck masses. Patients were initially treated by chemotherapy (n = 1), radiotherapy (n = 1), or chemotherapy plus radiotherapy (n = 6); and all patients subsequently underwent neck dissection for persistence of their neck masses. Histologically, the neck lesions were characterized by a foreign-body giant-cell reaction to keratin and extensive scarring. None (0%) of the patients developed recurrent regional disease in the treated neck. Two (25%) of the patients had tumor recurrence at the primary site. Two (25%) of the patients developed widely metastatic disease. CONCLUSIONS: These observations suggest that squamous cell granulomas represent histologic regression of metastatic squamous cell carcinoma in patients with HNSCC treated by chemotherapy and/or radiotherapy. Although persistent cervical adenopathy is an established risk factor for locoregional failure in this group of patients, squamous cell granulomas of the neck paradoxically may reflect enhanced regional tumor sensitivity to cytotoxic agents.

Adult↗