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Biomedical subjects

E E Vokes

Publications and source records attributed to E E Vokes.

At least 37 records · Page 2Linked to original sources
PubMed2001

Trends and perspectives in multimodality therapy of locoregionally advanced non-small cell lung cancer.

In recent years progress has been made in the therapy of patients with stage III non-small cell lung cancer. Induction chemotherapy and concomitant chemoradiotherapy have been proven to be superior to radiation therapy alone for unresectable stage disease. In direct comparisons of induction and concomitant chemoradiotherapy, the latter has been found to lead to higher median survival times, albeit at the cost of increased toxicity within the irradiated field. Additional trials have explored the administration of both induction chemotherapy and concomitant chemoradiotherapy in sequence and the integration of the taxanes, gemcitabine and vinorelbine and irinotecan into the multimodality therapy setting. These and other novel concepts are discussed.

Antineoplastic Agents↗
PubMed2001

Chemotherapy in the management of squamous-cell carcinoma of the head and neck.

Previously reserved for palliation, chemotherapy is now also a central component of several curative approaches to the management of patients with advanced-stage head and neck cancer. Here we review the results of both induction chemotherapy and chemoradiotherapy trials in patients with curable disease, and chemotherapy trials in patients with recurrent and metastatic disease, and we highlight current areas of investigation. Compared with traditional treatment modalities, chemotherapy given on induction schedules to patients with advanced laryngeal cancer allows greater organ preservation without compromise to survival; when given concomitantly with radiotherapy to patients with resectable or unresectable advanced disease, chemotherapy again improves survival.

Antineoplastic Agents↗
PubMed2001

Phase II studies of bryostatin-1 in patients with advanced sarcoma and advanced head and neck cancer.

BACKGROUND: Bryostatin 1 is a marine derived macrolactone with antineoplastic activity modulated through protein kinase C, and with good activity in in vitro and in vivo models. There are few drugs that offer palliation for metastatic soft-tissue sarcoma and head and neck cancer, and drugs with new mechanisms of action warrant detailed disease specific study. PATIENTS AND METHODS: Two phase II studies for patients with incurable soft tissue sarcoma (12), or head and neck cancer (12) were conducted. Patients were treated with bryostatin, 120 mg/m2/72 hours every 2 weeks for 3 cycles prior to re-evaluation. Most patients had received prior chemotherapy. RESULTS: No patients had objective responses to therapy. Six patients had brief periods of disease stabilization. Toxicity was generally mild, with myalgia being prominent (n=8). Hyponatremia, not previously described, occurred in 5 patients. The mechanism of this toxicity was unclear. CONCLUSIONS: Bryosytatin 1 given as a single agent for advanced adult soft tissue sarcoma and head and neck cancer is inactive. Myalgia and hyponatremia were the predominant toxicities.

Adult↗
PubMed2001

A phase I trial of the oral platinum analogue JM216 with concomitant radiotherapy in advanced malignancies of the chest.

JM216 is an orally administered platinum analogue. We undertook this study to determine the maximally tolerated dose (MTD) of JM216 when administered with concomitant radiotherapy to the chest (200 cGy daily, 5 x/week) in patients with locoregionally advanced non-small cell lung (NSCLC) or esophageal cancer. Patients were excluded for inadequate bone marrow reserve, prior radiotherapy to the primary tumor or previous treatment with platinum drugs. A dose-limiting toxicity (DLT) was defined using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) and consisted of grade > or = 2 renal, hepatic, cardiac, or pulmonary toxicity or grade > or = 3 hematologic, neurological, or gastrointestinal toxicity. A total of 23 patients were registered; two never received treatment and are excluded from analyses. Six patients were treated at a dose of 30 mg/m2/day for 5 days with two grade 2 DLT's: cough (1 pt) and elevated trans-aminases (1 pt). Seven evaluable patients were treated at 60 mg/m2/day and seven experienced grade 3 or 4 toxicity, five related to myelosuppression. The dose was then reduced to 45 mg/m2/d. Eight patients were evaluable for toxicity, of which 5 experienced DLT: myelosuppression (3 pts), esophagitis (2 pts), dyspnea (1 pt), and elevated creatinine (1 pt). Fourteen patients were evaluable for efficacy, of which 6 had an objective response, including one complete response. The recommended phase II dose of JM216 with concurrent radiation therapy is 30 mg/m2/d for 5 days. The major DLT is myelosuppression with only limited increased toxicity within the field of radiation. This conceivably may limit the use of JM216 as a radiation sensitizer.

Administration, Oral↗
PubMed2001

A phase II trial of 9-aminocaptothecin (9-AC) as a 120-h infusion in patients with non-small cell lung cancer.

In a previous phase II trial of the synthetic topoisomerase I inhibitor, 9-aminocamptothecin (9-AC), given as a 72-h infusion, we identified modest single agent activity of 9% in patients with previously untreated advanced non-small cell lung cancer (NSCLC). Preclinical studies suggested that a more prolonged continuous infusion of the drug might lead to greater antitumor activity. A phase I study recommended a phase II dose of 25 microg/m2/hr for 120 h (3000 microg/m2 over 5 days), administered for 2 consecutive weeks of a 3-week cycle. We utilized this schedule and enrolled 13 chemotherapy-naïve patients with Stage IIIB and IV NSCLC in this trial: median age 67 (range 57-74); 46% male; 92% stage IV; and median performance status 1. Twelve patients are available for response and toxicity evaluation after 2 cycles of therapy. One patient achieved a partial response. Four patients had stable disease while seven patients had progressive disease. Patients with stable or progressive disease after two cycles received no additional 9-AC, and were offered conventional chemotherapy. The median survival time was 10.2 months and the one-year survival rate 28% (95% confidence interval, 5-58%). Significant toxicities included myelosuppression, fatigue, and anorexia. One patient had grade 4 neutropenia following the first week of cycle 2, and did not receive additional therapy. There were no neutropenia-related infections. These data suggest that this prolonged schedule is unlikely to increase 9-AC's very modest activity in NSCLC above that seen with the simpler 72-h administration schedule. Further evaluation of 9-AC in NSCLC is not recommended.

Aged↗
PubMed2001

Sequential induction chemotherapy and concomitant chemoradiotherapy in the management of locoregionally advanced laryngeal cancer.

PURPOSE: To determine overall survival, progression-free survival, rate of voice preservation, and patterns of failure in locoregionally advanced laryngeal cancer treated with induction chemotherapy with or without surgery followed by concomitant chemoradiation. BACKGROUND: Locoregionally advanced laryngeal cancer has been conventionally treated with either surgery and adjuvant radiotherapy or radiotherapy alone, and clinical and functional outcomes have been poor. Chemoradiotherapy has been demonstrated to improve functional outcome and disease control over conventional treatment in recent randomized head and neck trials. PATIENTS AND METHODS: Advanced head and neck cancer patients were enrolled onto two consecutive phase II studies. Induction treatment consisted of three cycles of cisplatin, 5-fluorouracil (5-FU), leucovorin, and interferon-alpha 2b (PFL-IFN) followed by surgery for residual disease. Surgical intent was to spare the larynx when possible. All patients then proceeded to concomitant chemoradiation consisting of seven or eight cycles of 5-FU, hydroxyurea, and a planned total radiotherapy dose of 7000 cGy (FHX). RESULTS: A subset of thirty-two laryngeal cancer patients with predominantly stage IV disease comprises the study group for this report. Clinical CR was observed in 59% of patients following induction therapy. The median follow-up was 63.0 months for surviving patients and 44.5 months for all patients. At five years, overall survival is 47%, progression-free survival is 78%, and locoregional control is 78%. No distant failures were observed. Voice preservation with disease control was 75% at five years. Only two total laryngectomies were performed during the course of treatment and follow-up. Treatment-related toxicity accounted for two deaths. CONCLUSIONS: The addition of concomitant chemoradiotherapy to induction chemotherapy for locoregionally advanced laryngeal cancer appears to increase locoregional control and survival rates. PFL-IFN-FHX resulted in high rates of disease cure and voice preservation in a group of patients that has traditionally fared poorly in both clinical and functional outcome.

Aged↗
PubMed2001

Induction chemotherapy followed by concomitant chemoradiotherapy for non-small cell lung cancer.

Multiple concepts of combined modality therapy for locoregionally advanced inoperable non-small cell lung cancer have been investigated. These include induction chemotherapy, concomitant chemoradiotherapy, and intensified radiation therapy schedules. To date, induction chemotherapy has been validated in randomized prospective trials versus radiotherapy alone. Concomitant chemoradiotherapy has led to promising results when combination chemotherapy regimens were used in the phase II setting. In addition, concomitant chemoradiotherapy has been shown to be superior to induction chemotherapy in direct comparison. Finally, accelerated radiotherapy has been shown to lead to improved locoregional control and survival in one randomized study. Based on these observations, the Cancer and Leukemia Group B (CALGB study 9431) investigated the addition of either vinorelbine, paclitaxel, or gemcitabine to cisplatin. In this trial, patients with locally advanced and inoperable non-small cell lung cancer received two cycles of induction chemotherapy with an additional two cycles of concomitant chemoradiotherapy utilizing the same agents accompanied by standard radiation to a total dose of 66 Gy. One hundred eighty-seven patients were entered on this study. An early analysis showed the median survival time was 17 months for all patients entered on the trial. In the context of other CALGB studies, the data from this trial are encouraging, and the regimens used warrant further study.

Adult↗
PubMed2001

Treatment of head and neck and esophageal xenografts employing Alimta and concurrent ionizing radiation.

We examined the interaction between Alimta and ionizing radiation (IR) as a potential strategy to enhance the therapeutic ratio of combined-modality cancer treatment. Mice bearing human esophageal adenocarcinoma xenografts (Seg-1) or squamous cell carcinoma xenografts (SQ-20B) were treated with Alimta and IR employing a fractionated treatment schedule. Treatment with Alimta alone slowed the growth of Seg-1 but not SQ-20B tumors compared with control tumors. In Seg-1 xenografts combined treatment with Alimta and IR produced significant tumor growth inhibition compared with Alimta alone or IR alone. In SQ-20B xenografts, treatment with Alimta did not enhance IR-mediated tumor growth inhibition suggesting that sensitivity to Alimta is necessary for an interactive cytotoxic effect with IR. The present data suggest the potential clinical efficacy of combining Alimta administration with radiotherapy for Alimta-sensitive cells and indicate that further testing needs to be conducted to optimize the dosing schedule to enhance the interaction between the therapeutic agents.

Adenocarcinoma↗
PubMed2001

Elimination pathways of [14C]losoxantrone in four cancer patients.

Losoxantrone is an anthrapyrazole derivative in Phase III development in the U.S. for solid tumors, notably breast cancer. To obtain information on the routes of elimination of the drug, a study was conducted in four patients with advanced solid tumors, which involved intravenous administration of 100 microCi of [14C]losoxantrone for a total dose of 50 mg/m(2) during the first course of losoxantrone therapy. Blood, urine, and feces were collected for up to 2 weeks and were analyzed for total radioactivity and parent drug. In addition, feces were profiled for the presence of metabolites. Plasma concentrations of total radioactivity exhibited a temporal pattern similar to the parent drug. Combined recovery of administered total radioactivity from urine and feces was 70% with the majority (87%) of this radioactivity excreted in the feces, presumably via biliary excretion. Feces extracts were profiled for metabolites using a high-performance liquid chromatography method developed to separate synthetic standards of previously identified human urinary metabolites. Only intact losoxantrone was found in the feces. About 9% of the dose was excreted in the urine, primarily during the first 24 h and mostly in the form of parent compound. Collectively, these data indicate that fecal excretion of unmetabolized drug via biliary and/or intestinal excretion is the primary pathway of intravenously administered losoxantrone elimination in cancer patients with refractory solid tumors.

Anthraquinones↗
PubMed2001

Docetaxel (Taxotere) in combination with radiation therapy and the potential of weekly administration in elderly and/or poor performance status patients with advanced non-small cell lung cancer.

A randomized phase II trial conducted by the Cancer and Leukemia Group B in patients with unresectable non-small cell lung cancer showed that induction chemotherapy followed by concurrent radiotherapy and chemotherapy was feasible when cisplatin was administered together with either gemcitabine, vinorelbine, or paclitaxel. The dominant toxicity was esophagitis. Preliminary survival data are encouraging. Other trials in progress or planned will elucidate the relative contributions of induction and concurrent therapy to outcome. A phase I study has shown that it is feasible to combine docetaxel (Taxotere: Aventis, Antony, France) with concomitant radiotherapy in patients with advanced non-small cell lung or esophageal cancer. Giving the drug once every 3 weeks during standard radiotherapy, the maximum tolerated dose is 40 mg/m2 per cycle. The dose-limiting toxicities are neutropenia and esophagitis. However, it is possible to escalate the total docetaxel dose to 60 mg/m2 per cycle by weekly administration of 20 mg/m2. Beyond this point, esophagitis is dose limiting. In the palliative-intent treatment setting, the weekly administration of docetaxel is also likely to be a helpful new approach to administering the drug in subgroups of patients such as the elderly and those with concomitant disease. Weekly docetaxel (36 mg/m2/wk) was administered to patients with advanced non-small cell lung cancer who were elderly (median age, 71 years) or had poor performance status. In this unfavorable group, weekly docetaxel produced a 19% objective response rate and with further follow-up, 1-year survival is 28%. This level of activity is similar to other single agents recently evaluated in more favorable patient groups. The lack of myelosuppression seen with weekly administration suggests that the dose intensity of docetaxel could be maintained in combination regimens.

Aged↗
PubMed2001

The impact of smoking status, disease stage, and index tumor site on second primary tumor incidence and tumor recurrence in the head and neck retinoid chemoprevention trial.

Second primary tumors (SPTs) develop at an annual rate of 3-7% in patients with head and neck squamous cell cancer (HNSCC). In a previous Phase III study, we observed that high doses of 13-cis-retinoic acid reduced the SPT rate in this disease. In 1991, we launched an intergroup, placebo-controlled, double-blind study to evaluate the efficacy of low-dose 13-cis-retinoic acid in the prevention of SPTs in patients with stage I or II squamous cell carcinoma of the larynx, oral cavity, or pharynx who had been previously successfully treated with surgery, radiotherapy, or both, and whose diagnoses had been established within 36 months of study entry. As of September 16, 1999, the Retinoid Head and Neck Second Primary (HNSP) Trial had completed accrual with 1384 registered patients and 1191 patients randomized and eligible. All of the patients were followed for survival, SPT development, and index cancer recurrence. Smoking status was assessed at study entry and during study. Smoking cessation was confirmed biochemically by measurement of serum cotinine levels. The annual rate of SPT development was analyzed in terms of smoking status and tumor stage. As of May 1, 2000, SPTs have developed in 172 patients. Of these, 121 (70.3%) were tobacco-related SPTs, including 113 in the aerodigestive tract (57 lung SPTs, 50 HNSCC SPTs, and 6 esophageal SPTs) and 8 bladder SPTs. The remaining 51 cases included 23 prostate adenocarcinomas, 8 gastrointestinal malignancies, 6 breast cancers, 3 melanomas, and 11 other cancers. The annual rate of SPT development observed in our study has been 5.1%. SPT development related to smoking status was marginally significant (active versus never, 5.7% versus 3.5%; P = 0.053). Significantly different smoking-related SPT development rates were observed in current, former, and never smokers (annual rate = 4.2%, 3.2%, and 1.9%, respectively, overall P = 0.034; current versus never smokers, P = 0.018). Stage II HNSCC had a higher overall annual rate of SPT development (6.4%) than did stage I disease (4.3%; P = 0.004). When evaluating the development of smoking-related SPTs, stage was also highly significant (4.8% for stage II versus 2.7% for stage I; P = 0.001). Smoking-related SPT incidence was significant for site as well (larynx versus oral cavity, P = 0.015; larynx versus pharynx, P = 0.011). Primary tumors recurred at an annual rate of 2.8% in a total of 97 patients. The rate of recurrence was higher in patients with stage II disease (4.1% versus 2.2%, P = 0.004) as well as oral cavity site when compared with larynx (P = 0.002). This is the first large-scale prospective chemoprevention study evaluating smoking status and its impact on SPT development and recurrence rate in HNSCC. The results indicate significantly higher SPT rates in active smokers versus never smokers and significantly higher smoking-related SPT rates in active smokers versus never smokers, with intermediate rates for former smokers.

Adult↗
PubMed2000

Lung cancer.

Lung cancer remains a major worldwide health problem, accounting for more than a sixth of cancer deaths. The proportion of cancers that are adenocarcinomas is increasing in North America and to some degree in Europe, leading to a changing clinical picture characterised by early development of metastases. Newer diagnostic techniques have allowed for more accurate tumour staging and treatment planning. In patients with non-small-cell cancer, surgical resection offers substantial cure rates in early-stage cases. Combined chemotherapy plus radiation therapy has clearly improved the treatment results for patients with locally advanced cancers, and patients with metastatic disease are now candidates for newer chemotherapy regimens with more favourable results than in the past. Small-cell lung cancer is highly responsive to chemotherapy, and recent advances in radiation therapy have improved the prospects for long survival. New techniques for screening, and innovative approaches to both local and systemic treatment offer hope for substantial progress against this disease in the near future.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Swallowing function in patients with head and neck cancer prior to treatment.

OBJECTIVE: To define the site-specific swallowing dysfunctions of patients with head and neck cancer with respect to tumor site and stage by, videofluoroscopic oropharyngeal motility (OPM) study prior to initiation of treatment. DESIGN: Retrospective survey. SETTING: Academic university institution. PATIENTS: A consecutive sample of 79 patients with stage III or IV head and neck cancer without prior treatment or tracheotomy. Patients were divided into groups according to tumor site: oral cavity (n = 7), oropharynx (n = 27), larynx (n = 24), and hypopharynx (n = 10). Patients with sinonasal, nasopharyngeal, and unknown primary carcinomas served as the comparison group (n = 11). INTERVENTION: All patients underwent OPM study prior to treatment. MAIN OUTCOME MEASURES: Parameters of swallowing function, including oral impairment, pharyngeal impairment, cervical esophageal impairment, aspiration, and Swallowing Performance Status Scale (SPSS) score (a global measure of swallowing function) were extracted from the pretreatment OPM study and analyzed with reference to tumor site, T stage, and overall stage. The relations between tumor site and area or degree of dysfunction, and between stage of disease and area or degree of dysfunction were analyzed using chi2 and Fisher exact tests. RESULTS: Aspiration status, cervical esophageal impairment, and pharyngeal impairment examined as a function of disease site showed statistically significant differences between groups, with laryngeal and hypopharyngeal sites revealing the most severe dysfunctions. The SPSS score did not correlate with tumor site, T stage, or overall stage. Other OPM parameters analyzed as a function of T stage and overall stage revealed no consistent patterns. CONCLUSIONS: Hypopharyngeal and laryngeal disease sites have a high degree of pretreatment functional impairment. The SPSS score is a good global measure of swallowing dysfunction. In addition, significant site-specific dysfunctions are found when the OPM study is analyzed via its separate parameters. It is therefore critical that posttreatment function is compared with baseline pretreatment dysfunction.

Adolescent↗
PubMed2000

The role of cervical lymphadenectomy after aggressive concomitant chemoradiotherapy: the feasibility of selective neck dissection.

OBJECTIVES: To evaluate the necessity, technical feasibility, and complication rate of neck dissection performed on patients with head and neck cancer after 5 cycles of concomitant chemoradiotherapy (CRT) and to justify a selective neck dissection (SND) approach and define the optimal timing of post-CRT neck dissection. DESIGN AND SETTING: Retrospective analysis in an academic university medical center. PATIENTS: Sixty-nine eligible patients with advanced (stage III and IV) head and neck cancer who have undergone 1 of 4 CRT protocols. Patients ranged in age from 36 to 75 years, and surgical procedures were performed over a 4-year period. Follow-up ranged from 6 to 64 months. INTERVENTION: Neck dissection (most commonly unilateral SND) performed within 5 to 17 weeks after CRT completion. MAIN OUTCOME MEASURES: Complication rate and incidence of positive pathology (viable cancer) in pathologic neck dissection specimens. RESULTS: Seven (10%) of 69 patients developed wound healing complications, 4 (6%) of whom required surgical intervention for ultimate closure. There were no wound infections. Other complications occurred in 11 (16%) of 69 patients and included need for tracheotomy, nerve transection and paresis, and permanent hypocalcemia. Twenty-four (35%) of 69 patients revealed microscopic residual disease. Ten (50%) of 20 patients with N3 neck disease had positive pathology, whereas 14 (36%) of 39 patients with N2 disease had viable carcinoma in the dissection specimen (P =.09 by chi(2) analysis). There was no significant relation between radiologic complete response or partial response and residual microscopic cancer. In 1 patient, disease recurred in the neck after dissection. Mean follow-up time was 30.3 months. CONCLUSIONS: (1) Neck dissection for patients with N2 or greater neck disease after CRT is necessary to eradicate residual disease. (2) The complication rate of SND after CRT with hyperfractionated radiotherapy is low. (3) SNDs are technically feasible when performed within the "window" between the acute and chronic CRT injury (4-12 weeks). (4) SNDs, rather than more radical procedures, appear to be therapeutically appropriate in this group of patients because of the low incidence of disease recurrence in the neck.

Adult↗
PubMed2000

Sex-associated differences in survival of patients undergoing resection for lung cancer.

BACKGROUND: The increasing incidence of lung cancer among women prompted us to assess whether sex-associated differences exist in the presentation and survival of patients who undergo major lung resection for lung cancer. METHODS: We performed a retrospective review of patients who had major lung resection for lung cancer from January 1980 to June 1998. RESULTS: There were 265 men and 186 women. Women were younger (60.7+/-0.8 versus 63.6+/-0.6 years; p = 0.005). Adenocarcinoma was more common among women (48% versus 40%; p = 0.001). Pathologic stages for men were: I = 43%, II = 26%, IIIA = 25%, IIIB or IV = 6%, and for women: I = 52%, II = 20%, IIIA = 22%, IIIB or IV = 6% (p = 0.146). Median survival was better for women (41.8 versus 26.9 months; p = 0.006). This was due both to a difference in stage at presentation and to a better median survival rate for adenocarcinoma compared with squamous cell cancer. The data suggest an association between sex and survival, although this failed to reach statistical significance. Sex influenced survival with a relative risk for women of 0.67 (95% confidence interval 0.35 to 1.29; p = 0.231 adjusted for stage, cell type, age, and spirometry). CONCLUSIONS: There are sex-associated differences in the presentation and possibly in the survival of patients with lung cancer. This finding has possible implications regarding the selection of patients for therapy and for the design of randomized therapeutic trials.

Adenocarcinoma↗
PubMed2000

Paclitaxel/ifosfamide or navelbine/ifosfamide chemotherapy for advanced non-small cell lung cancer: CALGB 9532.

In order to explore non-cisplatin containing regimens for advanced non-small cell lung cancer, Cancer and Leukemia Group B conducted a randomized Phase-II study of two novel combinations, paclitaxel/ifosfamide and vinorelbine/ifosfamide. Both regimens were active with a 38% response rate (95% CI: 24%, 53%) and 31% (95% CI: 18%, 47%), respectively. Median survivals were 8.5 and 7.4 months. Toxicity, mostly neutropenia, was acceptable. These two combinations establish a 'proof of principle' that non-cisplatin containing regimens also have activity in this setting.

Adult↗
PubMed2000

CI-980 in advanced melanoma and hormone refractory prostate cancer.

INTRODUCTION: CI-980 is a novel chemotherapeutic agent that inhibits polymerization of tubulin. Preclinical studies have indicated a high level activity of this agent against various tumor cell lines. METHODS: 13 malignant melanoma patients who had failed prior chemotherapy and/or immunotherapy and 13 hormone refractory prostate cancer patients, including 4 who had received prior chemotherapy, were treated in 2 separate NCI-supported clinical trials. Subjects received a recommended phase II dose of CI-980 of 4.5 mg/m2/day by continuous infusion for 72 hours every 3 weeks. RESULTS: No activity was seen in either study. Toxicity was tolerable with neutropenia being the most common, significant toxicity. Among the melanoma patients, 15% and 31% developed grade 3 and grade 4 neutropenia, while 7% and 38% of the prostate patients developed grade 3 and grade 4 neutropenia, respectively. CONCLUSIONS: CI-980 at this dose and schedule is ineffective against malignant melanoma and hormone refractory prostate cancer.

Adult↗