PubMed Health⌕ Search

Biomedical subjects

Bonnie S Glisson

Publications and source records attributed to Bonnie S Glisson.

At least 19 recordsLinked to original sources
PubMed2006

Phase I/II study of docetaxel, cisplatin, and concomitant boost radiation for locally advanced squamous cell cancer of the head and neck.

PURPOSE: To investigate the feasibility of combining concomitant boost accelerated radiation with docetaxel and cisplatin and assess the regimen's toxicity, locoregional control rate, and survival in patients with locally advanced head and neck cancer (HNSCC). PATIENTS AND METHODS: Patients with stage III-IV HNSCC were eligible. Phase I included two schedules of docetaxel and cisplatin: arm 1, once per week during weeks 1 to 4; arm 2, every 21 days for weeks 1 and 4. Radiation consisted of 72 Gy in 42 fractions over 6 weeks (concomitant boost). RESULTS: Twenty patients were enrolled in phase I. The arm 1 maximum-tolerated dose (MTD) was defined at docetaxel 15 mg/m2 and cisplatin 20 mg/m2 based on prolonged mucositis in 29% of patients. The initial dose level in arm 2 was above the MTD. In total, 52 patients were treated using the arm 1 regimen in phase II. Acute toxicity included grade 3 mucositis and dermatitis in 81% and 44% of patients. The 2-year locoregional control rate was 71%. The 2-year progression-free and overall survival rates were 61% and 65%. Median survival was 37.8 months. Late effects included feeding tube dependence in 17% of patients alive and free of disease. CONCLUSION: Locoregional control, survival, and acute toxicity with this regimen were comparable with other trials utilizing taxanes and/or platins and concomitant conventional or altered fractionation radiation. Our data suggest that chemotherapy added to concomitant boost fractionation may increase rates of long-term feeding tube dependence. Phase III trials are needed to assess the contribution of concomitant boost fractionation to chemoradiotherapy.

Adult↗
PubMed2006

Phase I studies of imatinib mesylate combined with cisplatin and irinotecan in patients with small cell lung carcinoma.

BACKGROUND: Small cell lung carcinoma (SCLC) cell lines commonly express KIT and its ligand, stem cell factor, suggesting an autocrine loop promoting cell growth. Imatinib inhibits KIT kinase activity. SCLC cells treated with imatinib in vitro undergo cell cycle arrest. Imatinib reduces resistance to irinotecan in vitro. Common metabolic pathways suggest there may be drug interactions between imatinib and irinotecan or cisplatin. In the current study, the authors investigated the feasibility of combining these drugs in the treatment of patients with SCLC. METHODS: Two Phase I studies were conducted independently at two institutions. Patients with extensive-disease SCLC underwent therapy with cisplatin, irinotecan, and imatinib using two similar regimens. In one study, immunohistochemical analysis of the expression of potential imatinib targets was performed on pretreatment biopsy specimens, and blood specimens were collected and analyzed for imatinib, irinotecan, and cisplatin pharmacokinetic parameters. RESULTS: Nine patients were enrolled and were evaluable for toxicity. A high incidence of neutropenia, diarrhea, and thrombosis was observed that precluded dose escalation. Six patients were evaluable for response after four cycles; five patients experienced a partial response and the other patient had developed progressive disease. Four of six tumor specimens tested expressed platelet-derived growth factor receptor-alpha and two expressed KIT. Irinotecan clearance was found to be significantly decreased by imatinib (P < 0.04). No significant alteration in the disposition of cisplatin was observed. CONCLUSIONS: The maximum tolerated dose for this combination with granulocyte-colony-stimulating factor support was identified as imatinib at a dose of 300 mg/day with irinotecan (at a dose of 65 mg/m(2)) and cisplatin (at a dose of 30 mg/m(2)) given on Days 1 and 8, every 21 days. The decreased irinotecan clearance may explain the high incidence of diarrhea and neutropenia noted in the current study.

Adult↗
PubMed2006

Asian ethnicity as a predictor of response in patients with non-small-cell lung cancer treated with gefitinib on an expanded access program.

BACKGROUND: The primary objective of this retrospective study was to investigate the potential role of East Asian ethnicity or origin in predicting response to gefitinib in advanced-stage non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A chart review was done of all patients treated with gefitinib at M. D. Anderson Cancer Center on the Expanded Access Program. RESULTS: There were 223 patients with advanced-stage NSCLC who were enrolled. Of these, 182 received >or= 1 dose, and 160 were evaluable for response. The partial response rate was 8.8%, and the stable disease rate was 26.3%. Median time to progression was 2.5 months, and median survival was 6.8 months. The 1- and 2-year survival rates were 35.3% and 12.4%, respectively. Partial responses were seen in 7 of 12 patients (58.3%) of East Asian origin compared with 7 of 131 patients who were white (5.3%). This difference was statistically significant when controlling for histology, smoking status, hemoglobin, and diarrhea. Never smoking and diarrhea were also independent predictors of response. CONCLUSION: For the first time, in a multivariate analysis, we observed a positive relationship between East Asian origin and response to gefitinib. These findings might help determine which patients will likely benefit from gefitinib.

Adult↗
PubMed2005

Phase II study of pemetrexed in combination with carboplatin in the first-line treatment of advanced nonsmall cell lung cancer.

BACKGROUND: The primary objectives of this study were to determine the efficacy and tolerability of a pemetrexed-carboplatin combination as first-line therapy in patients with advanced nonsmall cell lung cancer. METHODS: Eligibility criteria included Zubrod performance status of 0 or 1, Stage IIIB (malignant effusion) or IV disease, and no prior chemotherapy. Treatment was pemetrexed 500 mg/m2 given intravenously and carboplatin area under the serum concentration-time curve = 6 given intravenously on Day 1 every 3 weeks for six cycles; patients could receive additional cycles at the discretion of the treating physician and patient. All patients received folic acid, vitamin B12, and dexamethasone prophylaxis. RESULTS: Fifty patients (31 men and 19 women) were treated. The median age was 62 years. Ninety-six percent of patients had Stage IV disease, and 88% had a performance status of 1. The median number of cycles was 6; 15 patients received 8 or more cycles. There was Grade 3/4 neutropenia in 11 (22%) and 2 (4%) patients, respectively; Grade 3/4 thrombocytopenia in 1 (2%) and 0 patients, respectively. Three patients (6%) experienced Grade 3 nonhematologic side effects (diarrhea, neutropenic pneumonia, and fatigue). No patients had sensory neuropathy or alopecia >Grade 1. The partial response rate was 24%, median time to progression 5.4 months, 1-year survival 56.0%, and median survival 13.5 months. CONCLUSIONS: This is an active, very well-tolerated regimen. Trials focused on how to integrate this doublet with novel agents are warranted.

Adult↗
PubMed2005

A phase I/II study of neoadjuvant chemotherapy followed by radiation with boost chemotherapy for advanced T-stage nasopharyngeal carcinoma.

PURPOSE: Local recurrence is the most common site of failure for locally advanced nasopharyngeal carcinoma (NPC) treated with neoadjuvant cisplatin/5-fluorouracil (PF) and definitive radiation at our center. Based on this, we studied the addition of chemotherapy during the boost phase of radiation after neoadjuvant PF for advanced T-stage (T3-T4) NPC. This strategy was based on theoretical radiosensitization with chemotherapy during accelerated repopulation of the tumor with relatively radioresistant clonogens. METHODS AND MATERIALS: Three cycles of neoadjuvant PF was followed by conventionally fractionated radiation with additional PF during the boost portion of the radiation course. An initial Phase I study was done to establish the maximum tolerated dose of concurrent PF. RESULTS: Forty-four patients were enrolled. Six patients in Phase I defined the MTD for concurrent PF as: cisplatin 10 mg/m2/day and PF 320 mg/m2/day, on Days 1-5 during Weeks 6 and 7 of radiation therapy based on dose-limiting toxicities of mucositis, neutropenia, and thrombocytopenia. Forty-one patients were treated with concurrent therapy per protocol: complete, partial, and minor responses were seen in 23, 16, and 2 patients, respectively. Progression-free and overall survival rates at 5 years were 55% (95% CI, 41-75%) and 66% (95% CI, 52-85%), respectively. Seven of 11 tumor-related deaths were due to local recurrence. Nine of 10 patients with local recurrence had T4-stage disease at presentation. Local control of T4 disease was achieved in 74% of patients overall, and in 25% (1/4) with World Health Organization (WHO) type 1, 76% (16/21) with WHO type 2, and 90% (9/10) with WHO type 3 histology. Common toxicities included mucositis, dermatitis, fatigue, vomiting, and weight loss. CONCLUSIONS: This regimen was feasible and associated with promising overall survival. Local recurrence remains the major reason for treatment failure in advanced T-stage NPC, especially WHO types 1 and 2. Other strategies to improve local control in these patients should be investigated.

Adolescent↗
PubMed2005

Phase II study of the farnesyltransferase inhibitor lonafarnib with paclitaxel in patients with taxane-refractory/resistant nonsmall cell lung carcinoma.

BACKGROUND: The authors evaluated the safety, tolerability, and efficacy of treatment using lonafarnib, a novel farnesyltransferase inhibitor (FTI), in combination with paclitaxel in patients with metastatic (Stage IIIB/V), taxane-refractory/resistant nonsmall cell lung carcinoma (NSCLC). METHODS: Patients with NSCLC who experienced disease progression while receiving previous taxane therapy or who had disease recurrence within 3 months after taxane therapy cessation were treated with continuous lonafarnib 100 mg orally twice per day beginning on Day 1 and paclitaxel 175 mg/m(2) intravenously over 3 hours on Day 8 of each 21-day cycle. RESULTS: A total of 33 patients were enrolled, 29 of whom were evaluable for response. Partial responses (PR) and stable disease (SD) were observed in 3 (10%) and 11 patients (38%), respectively. Thus, 48% (14 of 29) experienced clinical benefit (PR or SD). The updated and final median overall survival time was 39 weeks and the median disease progression-free survival time was 16 weeks. The combination of lonafarnib and paclitaxel was well tolerated with minimal toxicity. Grade 3 toxicities included fatigue (9%), diarrhea (6%), and dyspnea (6%). Grade 3 neutropenia occurred in only 1 patient (3%). Grade 4 adverse events included respiratory insufficiency in 2 patients (6%) and acute respiratory failure in 1 patient (3%). CONCLUSIONS: Lonafarnib plus paclitaxel demonstrated clinical activity in patients with taxane-refractory/resistant metastatic NSCLC. In addition, the combination of lonafarnib and paclitaxel was well tolerated with minimal toxicity. Evaluation of this combination therapy in additional clinical trials is warranted.

Adult↗
PubMed2005

Phase I study of thoracic radiation dose escalation with concurrent chemotherapy for patients with limited small-cell lung cancer: Report of Radiation Therapy Oncology Group (RTOG) protocol 97-12.

PURPOSE: The purpose of RTOG 97-12 was to determine the maximum tolerated dose (MTD) of thoracic radiation therapy (RT) with concurrent chemotherapy for patients with limited-stage small-cell lung cancer. PATIENTS AND METHODS: Sixty-four patients received four cycles of cisplatin (60 mg/m(2) i.v.) and etoposide (120 mg/m(2) i.v. Days 1-3) (PE), with concurrent thoracic RT starting on Day 1. Thoracic RT was given during the first two cycles with 1.8 Gy/fraction daily to the clinical target volume, followed by thoracic RT to the gross tumor volume b.i.d. for the last 3, 5, 7, 9, or 11 treatment days (total dose 50.4, 54.0, 57.6, 61.2, or 64.8 Gy, respectively). The MTD was based on the dose that produced Grades 3-4 nonhematologic toxicity (mainly esophagitis and pneumonitis) in greater than 50% of patients. RESULTS: After the first 8 patients were enrolled in Arm 1, administration of etoposide was changed from 120 mg/m(2) i.v. on Days 2 and 3 of each cycle to 240 mg/m(2) p.o. for patient convenience as outpatients. Total thoracic RT doses from 50.4 Gy to 61.2 Gy over 5 weeks given with PE were well tolerated. Three of the first 5 patients in the 64.8 Gy arm developed Grade 3 acute esophagitis; the MTD was determined to be 61.2 Gy. Fifty-four (87%) of the 62 evaluable patients achieved a complete (68%) or partial (19%) tumor response. The 18-month survival was 25% for patients receiving 50.4 Gy and 82% for those receiving 61.2 Gy. CONCLUSIONS: The MTD for this accelerated thoracic RT regimen with concurrent PE was 61.2 Gy over 5 weeks.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Neoadjuvant chemotherapy for squamous cell carcinoma of the oral tongue in young adults: a case series.

BACKGROUND: Squamous cell carcinoma of the oral tongue (SCCOT) in the young population has emerged as a growing worldwide health problem. Standard therapies, consisting primarily of surgery with possible adjuvant radiotherapy, have resulted in only modest improvements in survival in recent decades, whereas the treatments for SCCOT continue to impair oral function. With the increased use and improved functional results of neoadjuvant chemotherapy in the treatment of squamous cell carcinoma of other upper aerodigestive tract sites, we have reviewed our experience with neoadjuvant chemotherapy in young patients with SCCOT. METHODS: A retrospective review was conducted of all patients younger than 45 years (N = 49) with previously untreated SCCOT evaluated at a comprehensive cancer center from July 1995 to August 2001. Charts were reviewed to obtain demographic data, comorbidities, nutritional status, tumor status, treatment and response information, and follow-up data. RESULTS: Fifteen patients were identified who received neoadjuvant chemotherapy with taxane-based regimens before undergoing glossectomy and neck dissection. Thirteen of these patients (87%) exhibited stage III or IV disease at presentation, and all exhibited at least a partial response at the primary site. Pathologically positive nodes were identified in only six patients (40%), although 13 (87%) had clinically or radiographically suspicious nodes at presentation. Adjuvant radiation therapy was administered to seven patients (47%). With a median follow-up of 39 months, no patient has had local or regional recurrence, although three patients (20%) have had distant metastases develop; one patient with an isolated distant metastasis was successfully salvaged with radiation. By comparison during the same period, 34 young adult patients with SCCOT were treated with surgery with or without postoperative radiotherapy but without the use of chemotherapy. Although these patients had lower T classifications (18% vs 67% T3/T4; p = .0007), incidence of nodal metastases (15% vs 87% N+; p < .0001), and overall disease stage (24% vs 87% stage III/IV; p < .0001) than the neoadjuvant chemotherapy group, the overall survival (82%), disease-specific survival (88%), and recurrence-free survival (82%) of the surgery-first group was similar to that of the neoadjuvant chemotherapy group (87%, 87%, and 80%, respectively). CONCLUSIONS: This retrospective investigation demonstrates that neoadjuvant chemotherapy with taxane-based regimens may play a role in the successful treatment of SCCOT in young adult patients. Ultimately, this treatment plan may lead to improved functional outcomes in young patients with SCCOT by allowing function-sparing surgery and avoiding postoperative radiotherapy, without sacrificing disease control and survival, but a prospective trial is needed. We have initiated a prospective clinical trial to further investigate the impact of neoadjuvant chemotherapy in patients younger than 50 with SCCOT.

Adolescent↗
PubMed2004

Sinonasal malignancies with neuroendocrine differentiation: patterns of failure according to histologic phenotype.

BACKGROUND: Sinonasal neuroendocrine tumors are rare malignancies that are represented by a spectrum of histologies, including esthesioneuroblastoma (ENB), sinonasal undifferentiated carcinoma (SNUC), neuroendocrine carcinoma (NEC), and small cell carcinoma (SmCC). The authors reviewed their institutional experience to determine whether sinonasal neuroendocrine tumors of different histologies have distinct clinical characteristics that warrant individualized treatment approaches. METHODS: The authors treated 72 adults with pathologically proven, nonmetastatic, primary sinonasal neuroendocrine tumors from 1982 to 2002. There were 31 patients with ENB, 16 patients with SNUC, 18 patients with NEC, and 7 patients with SmCC. Patients with ENB usually were treated with local therapy alone (surgery and/or radiotherapy); only 3 of 31 patients (9.7%) received treatment (radiation) to regional lymphatics, and only 5 of 31 patients (16.1%) received chemotherapy. In contrast, patients with non-ENB histologies usually received chemotherapy (10 of 16 patients with SNUC, 12 of 18 patients with NEC, and 5 of 7 patients with SmCC), and nonsurgical locoregional therapy was used more frequently (6 of 16 patients with SNUC, 4 of 18 patients with NEC, and 5 of 7 patients with SmCC). RESULTS: The median follow-up for surviving patients was 81.5 months (range, 6-266 months). The Kaplan-Meier estimate of overall survival at 5 years was 93.1% for patients with ENB, 62.5% for patients with SNUC, 64.2% for patients with NEC, and 28.6% for patients with SmCC (P = 0.0029; log-rank test). The local control rate at 5 years also was superior for patients who had ENB (96.2%) compared with patients who had SNUC (78.6%), NEC (72.6%), or SmCC (66.7%) (P = 0.04). The regional failure (RF) rate at 5 years was 8.7% for patients with ENB, 15.6% for patients with SNUC, 12.9% for patients with NEC, and 44.4% for patients with SmCC. Additional late events increased the RF rate for patients with ENB to 31.9% at 10 years. The distant metastasis rate at 5 years was 0.0% for patients with ENB, 25.4% for patients with SNUC, 14.1% for patients with NEC, and 75.0% for patients with SmCC. CONCLUSIONS: This spectrum of malignancies with neuroendocrine features shares a common site of origin within the head and neck, but their natural histories appear to diverge into two main groups: ENB and non-ENB. Patients with ENB had excellent local and distant control rates with local therapy alone. Given the higher rates of systemic failure for patients with SNUC, NEC, and SmCC, the authors favor the use of combined-modality therapy for these patients.

Adolescent↗
PubMed2004

Phase I evaluation of docetaxel and topotecan for patients with advanced solid tumors.

BACKGROUND: The authors administered a combination of docetaxel and topotecan with granulocyte-colony-stimulating factor (G-CSF) support in a Phase I study to define the maximum tolerated dose (MTD) of this regimen. METHODS: Patients with advanced-stage solid tumors were eligible for this trial if they had a Zubrod performance status of </= 2 and normal renal, hepatic, and bone marrow function. No previous therapy with taxanes or topoisomerase inhibitors was allowed. The authors administered both docetaxel and topotecan in a dose-escalated manner until the MTD was reached. Docetaxel was given on Day 1 of each cycle before topotecan, which was administered intravenously on Days 1-3. Granulocyte-colony-stimulating factor (G-CSF) support with 5 microg/kg subcutaneous injections was initiated on Day 4 and continued until the absolute granulocyte count recovered to 2000/microL. Treatment cycles were repeated every 21 days. RESULTS: Of the 11 patients enrolled in the current study, all were evaluable for toxicity and 10 were evaluable for response. A median of three treatment cycles was received (range, one to nine treatment cycles). The dose-limiting toxicity was Grade 4 (according to the National Cancer Institute Common Toxicity Criteria for Adverse Events [version 2.0]). neutropenia with fever. The MTD was 75 mg/m2 of docetaxel on Day 1 and 1.4 mg/m2 of topotecan on Days 1-3. There was one complete response and one partial response in patients with nasopharyngeal carcinoma and one partial response in a patient with small cell lung carcinoma (SCLC). The response durations were 24 weeks, 29 weeks, and >/= 244 weeks, respectively. At the time of last follow-up, both patients with nasopharyngeal carcinoma were still alive at 241 weeks and 244 weeks, respectively. CONCLUSIONS: This trial demonstrated that a regimen of docetaxel and topotecan with G-CSF support was generally well tolerated and had promising activity in patients with nasopharyngeal and SCLC.

Aged↗
PubMed2004

Phase I study of the farnesyltransferase inhibitor lonafarnib with paclitaxel in solid tumors.

PURPOSE: To establish the maximum tolerated dose of lonafarnib, a novel farnesyltransferase inhibitor, in combination with paclitaxel in patients with solid tumors and to characterize the safety, tolerability, dose-limiting toxicity, and pharmacokinetics of this combination regimen. EXPERIMENTAL DESIGN: In a Phase I trial, lonafarnib was administered p.o., twice daily (b.i.d.) on continuously scheduled doses of 100 mg, 125 mg, and 150 mg in combination with i.v. paclitaxel at doses of 135 mg/m(2) or 175 mg/m(2) administered over 3 h on day 8 of every 21-day cycle. Plasma paclitaxel and lonafarnib concentrations were collected at selected time points from each patient. RESULTS: Twenty-four patients were enrolled; 21 patients were evaluable. The principal grade 3/4 toxicity was diarrhea (5 of 21 patients), which was most likely due to lonafarnib. dose-limiting toxicities included grade 3 hyperbilirubinemia at dose level 3 (100 mg b.i.d. lonafarnib and 175 mg/m(2) paclitaxel); grade 4 diarrhea and grade 3 peripheral neuropathy at dose level 3A (125 mg b.i.d. lonafarnib and 175 mg/m(2) paclitaxel); and grade 4 neutropenia with fever and grade 4 diarrhea at level 4 (150 mg b.i.d. lonafarnib and 175 mg/m(2) paclitaxel). The maximum tolerated dose established by the continual reassessment method was lonafarnib 100 mg b.i.d. and paclitaxel 175 mg/m(2). Paclitaxel appeared to have no effect on the pharmacokinetics of lonafarnib. The median duration of therapy was eight cycles, including seven cycles with paclitaxel. Six of 15 previously treated patients had a durable partial response, including 3 patients who had previous taxane therapy. Notably, two of five patients with taxane-resistant metastatic non-small cell lung cancer had partial responses. CONCLUSIONS: When combined with paclitaxel, the recommended dose of lonafarnib for Phase II trials is 100 mg p.o. twice daily with 175 mg/m(2) of paclitaxel i.v. every 3 weeks. Additional studies of lonafarnib in combination regimens appear warranted, particularly in patients with non-small cell lung cancer.

Adult↗
PubMed2004

Effects of amifostine on acute toxicity from concurrent chemotherapy and radiotherapy for inoperable non-small-cell lung cancer: report of a randomized comparative trial.

PURPOSE: To determine the ability of amifostine to reduce the severity and/or incidence of the acute toxicities of concurrent chemotherapy and radiotherapy (RT) for non-small-cell lung cancer. METHODS AND MATERIALS: Patients with inoperable, nonmetastatic non-small-cell lung cancer receiving concurrent chemoradiotherapy were randomized to one of two treatment groups. Arm 1 patients received thoracic RT (total dose, 69.6 Gy in 58 fractions of 1.2 Gy b.i.d. 5 d/wk), plus oral etoposide (50 mg b.i.d. 30 min before thoracic RT for 10 days, repeated on Day 29) and cisplatin (50 mg/m2 i.v. on Days 1, 8, 29, and 36). Arm 2 patients received the same treatment plus amifostine (500 mg i.v. 20-30 min before any treatment the first 2 days of each week). Acute effects were assessed using the National Cancer Institute Common Toxicity Criteria. RESULTS: Sixty-two patients were enrolled between November 1998 and January 2001. The minimal follow-up was 24 months, and the median follow-up of living patients was 31 months. The patient and tumor characteristics were equally distributed between the patients in the two arms. The median survival time was 20 months in Arm 1 patients and 19 months in Arm 2 patients. The maximal esophageal toxicity was mild (Grade 1) in 23%, moderate (Grade 2) in 42%, and severe (Grade 3-4) in 35% of patients in Arm 1; the corresponding rates for the Arm 2 patients were 48%, 35%, and 16% (p = 0.021). Severe pneumonitis occurred in 16% of the Arm 1 and none of the Arm 2 patients (p = 0.020, chi-square test). Neutropenic fever occurred in 39% of Arm 1 and 16% of Arm 2 patients (p = 0.046, chi-square test). Mild hypotension, dysgeusia, and sneezing were significantly more frequent among the patients in Arm 2. CONCLUSION: Amifostine reduced the severity and incidence of acute esophageal, pulmonary, and hematologic toxicity resulting from concurrent cisplatin-based chemotherapy and RT. Amifostine had no apparent effect on survival in these patients with unresectable non-small-cell lung cancer, suggesting that it does not have a tumor-protective effect.

Adult↗
PubMed2004

Is concurrent chemoradiation the treatment of choice for all patients with Stage III or IV head and neck carcinoma?

BACKGROUND: Many patients with small primary tumors of the oropharynx have AJCC Stage III/IV disease on the basis of lymphadenopathy. In the current retrospective study, the authors hypothesized that these patients have high rates of locoregional control when treated with radiotherapy, either alone or combined with neck surgery, and may not require concurrent chemotherapy. METHODS: Two hundred ninety-nine patients met staging and inclusion criteria. Stage distribution was as follows: T1, 99 patients (33%); T2, 182 patients (61%); Tx, 18 patients (6%); N1, 74 patients (25%); N2, 170 patients (57%); N3, 39 patients (13%); and Nx, 16 patients (5%). Primary tumor resection or tonsillectomy had been performed in 36 patients (12%) and excisional lymph node biopsy or formal neck dissection in 192 patients (64%). Thirty-three additional patients (10%) received chemotherapy and were analyzed separately. RESULTS: The median follow-up was 82 months (range, 8-299 months). The actuarial 5-year rates of locoregional failure, distant metastases, and overall survival were 15%, 19%, and 64%, respectively. T status was associated with the 5-year rate of locoregional control: 95% for patients with T1-/Tx disease, compared with 79% for patients with T2 disease (P < 0.01). The 5-year rate of distant metastases for patients with N1/2a disease was 11%, compared with 28% for patients with N2b/N2c/N3 disease (P < 0.001). CONCLUSIONS: Patients with early-T status oropharyngeal carcinoma, which is considered advanced due to the presence of lymphadenopathy, have high rates of locoregional control when treated with radiotherapy without or with neck surgery. Local treatment intensification by the addition of concurrent chemotherapy to radiotherapy would not significantly benefit most of these patients.

Adolescent↗
PubMed2004

A Phase II study of docetaxel and carboplatin as neoadjuvant therapy for nasopharyngeal carcinoma with early T status and advanced N status.

BACKGROUND: Promising results from a Phase II trial of induction chemotherapy and sequential radiotherapy for advanced nasopharyngeal carcinoma (NPC) at The University of Texas M. D. Anderson Cancer Center (Houston, TX) and two retrospective reviews of the authors' historical experience with NPC demonstrated that distant failure was directly correlated with advanced lymph node status. Furthermore, local control was excellent for patients with T1-3 disease that was managed with radiation alone or with a sequential approach involving chemotherapy. Neoadjuvant chemotherapy (primarily with cisplatin + 5-fluorouracil) was associated with a significantly decreased risk of distant metastasis and with improved survival. Based on these findings, the authors evaluated a novel induction regimen involving docetaxel and carboplatin for patients with previously untreated T1-2N2-3M0 NPC. METHODS: Docetaxel (80 mg/m2 on Day 1) and carboplatin (to an area under the time-concentration curve of 6 on Day 1) were administered every 21 days for 3 cycles, after which radiotherapy was administered. NPC was restaged with magnetic resonance imaging and nasopharyngoscopy 3 weeks after the completion of chemotherapy and 6 weeks after the completion of radiotherapy. RESULTS: Over 5 years, 18 patients were enrolled in the study. Grade 4 neutropenia and Grade 2 fatigue were observed in 51% and 28% of chemotherapy courses, respectively. After chemotherapy, 2 patients had complete responses, 14 had partial responses, 1 had a minor response, and 1 had progressive disease. The latter two patients and one patient who had a partial response underwent off-study chemoradiotherapy. After radiotherapy or chemoradiotherapy, 12 patients had complete responses and 6 had partial responses. Seven patients had recurrent disease; two had local recurrences, and five had distant metastases. CONCLUSIONS: Although unlikely to be superior to cisplatin + 5-fluorouracil, the trial regimen could be administered quickly in the outpatient setting, was logistically more convenient for the patient, and was devoid of serious nonhematologic toxic effects. We believe that the risk-based approach examined in the current study merits further investigation.

Adult↗
PubMed2004

Trastuzumab in combination with cisplatin and gemcitabine in patients with Her2-overexpressing, untreated, advanced non-small cell lung cancer: report of a phase II trial and findings regarding optimal identification of patients with Her2-overexpressing disease.

The purpose of this study was to evaluate the feasibility, efficacy, safety, and pharmacokinetics of trastuzumab plus cisplatin and gemcitabine in patients with Her2-overexpressing stages IIIB or IV non-small cell lung cancer (NSCLC) and to study the relationship between results from the two methods for determining levels of Her2 overexpression. Chemonaive patients were eligible if they had stages IIIB or IV NSCLC with either a Her2 score of at least 1+ by immunohistochemical (IHC) analysis or a serum Her2 shed antigen level of at least 15 ng/ml by enzyme-linked immunosorbent assay (ELISA). Treatment consisted of cisplatin 75 mg/m(2) day one plus gemcitabine 1250 mg/m(2) days one and eight plus trastuzumab 4 mg/kg day one and 2 mg/kg weekly thereafter on a 21-day cycle for six cycles followed by weekly maintenance trastuzumab therapy. Of the 21 patients enrolled, 8 (38%) patients had a partial response. The 1-year survival rate was 62% (13/21). Median time to progression was 36 weeks. Pharmacokinetic studies revealed no interaction between trastuzumab and gemcitabine plus cisplatin. In patients screened for this study, Her2 expression was zero in 283/360 (79%); 1+ in 32/360 (9%); 2+ in 27/360 (8%); and 3+ in 18/360 patients (5%). Serum Her2 shed antigen was >15 ng/ml in 27/ 288 (9%) patients. Of patients who had both Her2 assays, 24% (4/17) with ELISA scores >15 ng/ml had IHC scores of 3+, compared with only 2% (3/145) of the patients <15 ng/ml and 4% (7/162) of all patients. The addition of trastuzumab to cisplatin and gemcitabine was well tolerated, but further study will be required to determine whether this combination is superior to chemotherapy alone. This may be demonstrated if only those patients with Her2, having a score of IHC 3+ were eligible. Since IHC 3+ is rare in NSCLC, performing IHC in only those patients with serum Her2 shed antigen >15 ng/ml would greatly increase the efficiency of IHC screening though at the cost of excluding nearly half the patients with Her2 scores of 3+ on IHC analysis. Thus, if sequential screening consisting of serum ELISA followed by IHC analysis is implemented, it may make a trastuzumab trial feasible but should ultimately be supplanted by another screening system if trastuzumab is shown to be beneficial to some patients with IHC Her2 scores of 3+.

Aged↗
PubMed2003

Management of nonsinonasal neuroendocrine carcinomas of the head and neck.

BACKGROUND: Nonsinonasal neuroendocrine carcinomas (NSNEC) of the head and neck are rare and pose a diagnostic and management challenge. The authors undertook a retrospective study to gain insights into the spectrum of clinicopathologic characteristics, patterns of failure, and optimal management of patients with this disease. METHODS: The authors treated 23 adults with pathologically proven, nonmetastatic, primary NSNEC from 1984 to 2001. The majority (13 patients) had laryngeal origin with the following American Joint Committee on Cancer stage distribution: Stage I disease in 1 patient, Stage II disease in 2 patients, Stage III disease in 6 patients, and Stage IV disease in 14 patients. Nine patients underwent definitive surgery with or without postoperative radiation, and 14 patients received definitive radiotherapy. The median definitive radiation dose was 66 grays (Gy) (range, 44-72 Gy) using conventional fractionation. Fourteen patients received chemotherapy, with two to four cycles of induction platinum plus etoposide used most commonly. RESULTS: The median follow-up time for surviving patients was 40 months (range, 15-89 months). The actuarial 2-year and 5-year overall survival (OS) rates were 53% and 33%, respectively; and the disease-free survival (DFS) rates were 41% and 25%, respectively. Both the 2-year OS rate (68% vs. 30%; P = 0.002) and the 2-year DFS rate (55% vs. 17%; P = 0.004) were improved with chemotherapy compared with local therapy alone. Seventy-five percent of patients with measurable disease had complete clinical responses to induction chemotherapy. There was 100% complete clinical response of tumor after radiotherapy. The actuarial 2-year local failure rate was 23%. Chemotherapy did not reduce local failure (P = 0.91). There was no regional failure. The 2-year and 5-year distant metastasis rates were 54% and 71%, respectively. The 2-year rates of metastases without and with chemotherapy were 79% and 39%, respectively (P = 0.006). The 2-year and 5-year rates of intracranial metastases were 25% and 44%, respectively, and the 2-year and 5-year rates of isolated brain metastases were 21% and 41%, respectively. CONCLUSIONS: Based on these results, the authors' treatment strategy for patients with NSNEC is sequential chemotherapy and radiation. They recommend full-dose radiotherapy alone for patients with NSNEC who achieve a complete clinical response to induction chemotherapy. Newer chemotherapeutic regimens or additional adjuvant chemotherapy should be investigated for patients with NSNEC given the high rate of distant failure. Due to the very high rate of brain metastases among patients in the current study, the authors now consider incorporating prophylactic cranial irradiation into primary radiotherapy for individual patients who have complete clinical responses to induction chemotherapy.

Adult↗
PubMed2003

Intraarterial cisplatin with intravenous paclitaxel and ifosfamide as an organ-preservation approach in patients with paranasal sinus carcinoma.

BACKGROUND: The objectives of this study were to determine the efficacy, organ-preservation rate, and safety of intraarterial (IA) cisplatin in combination with intravenous paclitaxel and ifosfamide in patients with locally advanced carcinoma of the paranasal sinuses who required orbital exenteration or major craniofacial resection for complete tumor resection. METHODS: Patients were treated with intravenous paclitaxel (135 mg/m(2)) on Day 1, ifosfamide (1000 mg/m(2)) on Days 1-3, sodium mercaptoethanesulfonate (600 mg/m(2)) on Days 1-3, and IA cisplatin (100 mg/m(2)) on Day 1 every 21 days. RESULTS: Of 24 study participants, 20 patients received at least 1 course of IA cisplatin, 1 patient had an early death, and 19 patients were evaluable for response. Five of those 19 patients (26%) achieved a complete response (CR), 6 patients (32%) achieved a partial response, and 8 patients (42%) had stable disease or developed progressive disease. Eye-sparing surgery followed by radiotherapy (RT) was feasible in 7 of 24 patients, RT was offered to only 7 patients, whereas 3 patients received chemotherapy and RT, 2 patients refused further therapy, 3 patients underwent craniofacial resection with orbitectomy, and 1 patient was treated systemically for metastatic disease. At the completion of treatment, 14 of 23 patients (61%) with locally advanced disease were disease free, and the orbit was preserved in 21 of 24 patients (88%). The overall survival, progression-free survival, and disease-free survival rates at 2 years were 60%, 50%, and 84%, respectively. Toxicity was substantial, with two patients experiencing cerebrovascular ischemia (one transient and one cerebrovascular accident) and three patients experiencing cranial neuropathy, which was reversible in two patients. CONCLUSIONS: Despite the encouraging organ-preservation rate, the approach studied resulted in substantial toxicity, and more effective adjunctive therapy is needed. Alternative approaches, including the integration of targeted therapy agents in induction chemotherapy regimens followed by concomitant chemotherapy and RT or eye-sparing surgery, need further exploration.

Adult↗
PubMed2003

Treatment of metastatic head and neck cancer: chemotherapy and novel agents.

For more than a decade, the de facto "standard of care" for palliative mangement of recurrent head/neck squamous carcinoma (HNSCC) has been the combination of cisplatin/5-flourouracil. With the advent of new cytotoxins, such as the taxanes, and of the molecularly targeted agents, eg., the EGFR inhibitors, the number of options for treatment in this setting has increased. However, none of these new approaches has yet been proven to be more effective than cisplatin/5-fluorouracil. Further, despite the pallitive intent of therapy in this setting, the palliative effects have been only infrequently assessed, with many studies relying on response as a surrogate for palliation. This chapter will focus on clinical and translational research efforts in the past decade focusing on the patient with incurable locoregionally recurrent or metastatic HNSCC. Ongoing and planned future trails will also be discussed.

Antineoplastic Agents↗