Biomedical subjects

J Dancey

Publications and source records attributed to J Dancey.

31 records · Page 2Linked to original sources

PubMed1999

Multitargeted antifolate LY231514 as first-line chemotherapy for patients with advanced non-small-cell lung cancer: A phase II study. National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To evaluate the efficacy and safety of the multitargeted antifolate LY231514 (MTA) in patients receiving initial chemotherapy for unresectable, advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with measurable, advanced NSCLC who had not received previous chemotherapy for advanced disease were considered for this study. Eligible patients who gave written informed consent initially received MTA 600 mg/m(2) intravenously (IV) for 10 minutes every 3 weeks. After three patients received treatment at this dose, the dose was reduced to 500 mg/m(2) IV at the same infusion time and frequency because of toxicity seen in this study and another Canadian MTA trial in colorectal cancer. Patients received up to four cycles after complete or partial remission or six cycles after stable disease was documented. RESULTS: Thirty-three patients were accrued onto the study. All were assessable for toxicity, and 30 patients were assessable for response. All but one patient had an Eastern Cooperative Oncology Group performance status score of 0 or 1, 18 patients (55%) had adenocarcinoma, and nine patients (27%) had squamous cell carcinoma. Twenty-five patients (76%) had stage IV disease, and the remainder had stage IIIB disease at trial entry. Seven patients experienced a confirmed partial response and no complete responses were seen; thus, the overall response rate was 23.3% (95% confidence interval, 9.9% to 42.3%). The median duration of response was 3.1 months (range, 2. 3 to 13.5 months) after a median follow-up period of 7.9 months. Four (67%) of six patients with stage IIIB disease and three (12.5%) of 24 with stage IV disease responded to treatment. Four patients (13.3%) experienced febrile neutropenia and 13 (39%) experienced grade 3 or 4 neutropenia, whereas only one patient (3%) developed grade 4 thrombocytopenia. Nonhematologic toxicity was generally mild or moderate, but 39% of patients developed a grade 3 skin rash. Most other toxicities comprised grade 1 or 2 stomatitis, diarrhea, lethargy, and anorexia. Ten patients stopped protocol therapy because of toxicity. CONCLUSION: MTA seems to have clinically meaningful activity as a single agent against advanced NSCLC. Toxicity is generally mild and tolerable. Further study of this agent in combination with cisplatin and other active drugs is warranted in this disease.

Adult↗

PubMed1998

A multicentre phase II study of carboplatin and prolonged oral etoposide in the treatment of cancer of unknown primary site (CUPS).

Cisplatin-based combination chemotherapy is frequently used to treat patients with carcinoma of unknown primary site (CUPS). Response rates in the literature range from 12% to 26% and median survival from 5 to 7 months. The goal of this study was to evaluate the combination of carboplatin and prolonged oral etoposide in patients with CUPS, with the hope of minimizing toxicity but improving efficacy and convenience. Treatment consisted of carboplatin, 300 mg m(-2) on day 1, and oral etoposide 50 mg on days 1-20, every 4 weeks for up to nine cycles. A total of 33 patients were treated and all were evaluable for toxicity. Non-haematological toxicity was mild to moderate, with the exception of one case of grade 4 stomatitis. Grade 4 leucopenia was observed in eight (24%) patients and sepsis in four (12%), with two and possibly three treatment-related deaths. For the 26 patients evaluable for response, the response rate was 23% with responses lasting a median of 11 months (range 7-13 months), with one patient still responding at 12 months. An additional nine patients (35%) had stable disease. Median survival for all patients was 5.6 months (range 2 weeks to 33 months). The combination of carboplatin with prolonged oral etoposide has moderate activity similar to that of other platinum-based regimens and is a well tolerated, convenient, outpatient regimen. Dosing according to estimated creatinine clearance to achieve a carboplatin AUC of 6.0 mg ml(-1) min might have decreased the incidence of severe myelotoxicity without compromising the regimen's efficacy.

Adenocarcinoma↗

PubMed1998

The psychosocial impact of bone marrow transplantation: a review of the literature.

Bone marrow transplant (BMT) is a procedure used for the treatment of a variety of cancers and malignant diseases. Recovery from this intensive process requires a long-term course, often accompanied by acute morbidity which includes various distressing physical symptoms. Recent literature has begun to explore the impact of this procedure on quality of life and psychosocial issues. While survivorship is often associated with a highly rated global quality of life, recovery from BMT is accompanied by several psychosocial difficulties which negatively impact patients. Fatigue is a common complaint, often hindering recipients for several years following their transplant. As well, reports of psychological distress, psychiatric symptoms, and/or mood disturbances such as anxiety or depression are not uncommon. Many patients also indicate interruption of sexual activity and increased sexual difficulty for several months following BMT. While some investigators have begun to examine hormone replacement therapy (HRT) as a treatment option for reducing sexual dysfunction, there is a general paucity of literature evaluating interventions for BMT survivors. This article reviews the literature examining various quality of life aspects including fatigue, psychosocial difficulties, and sexual functioning of patients during recovery from BMT. Limitations of past research are discussed and directions for future research suggested.

Bone Marrow Transplantation↗

PubMed1997

Non-small cell lung cancer: an overview of current management.

Non-small cell lung cancer (NSCLC) will remain a worldwide health problem for the foreseeable future. Unfortunately, local treatment of this disease is disappointing as most patients develop uncontrollable locally advanced or distant metastatic disease. The recent meta-analysis using updated patient data has suggested a potential role for adjuvant cisplatin-based chemotherapy (CT) in early stage disease, and has shown a significant, albeit modest, improvement in survival when combined with radiotherapy in locally advanced disease and as a single modality in metastatic disease. Although quality and cost of extra life with this more aggressive treatment need to be defined in prospective studies, CT should be considered standard treatment for patients with locally advanced and metastatic NSCLC able to receive cisplatin-based CT. Its role in stage I and II disease is under current investigation. Ongoing clinical studies with more active agents, novel combined modality treatment strategies and laboratory discoveries continue to emerge which may lead to valuable new treatment options to extend this survival advantage.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Quality of life scores: an independent prognostic variable in a general population of cancer patients receiving chemotherapy. The National Cancer Institute of Canada Clinical Trials Group.

This report examines the prognostic associations between QOL scores measured by the EORTC QLQ-C30 and survival in a large heterogeneous population of cancer patients. Eight hundred and fifty-one cancer patients who were to receive chemotherapy were enrolled in two National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) antiemetic trials. All patients completed the EORTC QLQ-C30 immediately prior to their first chemotherapy. Survival data were available and obtained for 474 of 639 patients (74%). Cox's proportional hazards model was used to assess the independent impact of QOL and demographic variables on survival. Presence of metastatic disease, diagnosis of lung or ovarian cancer, ECOG performance status, global quality of life and emotional functioning were significantly associated with survival. Global QOL was predictive in all patients, in subgroups of patients with metastatic disease, with breast and lung cancer and other tumour types. In patients with low global quality of life scores, patients with low emotional functioning ratings lived longer than did patients with high emotional functioning ratings. Patients with high global QOL live significantly longer than do patients with low global QOL. The relationship between emotional functioning in patients with low global QOL and survival needs confirmation.

Female↗

PubMed1996

Current perspectives on camptothecins in cancer treatment.

The camptothecins are a new class of chemotherapeutic agents which have a novel mechanism of action targeting the nuclear enzyme topoisomerase I. Knowledge of the structure-activity relationships of the parent compound camptothecin has led to the development of effective soluble analogues with manageable toxicities. Broad anti-tumour activity shown in preclinical studies has been confirmed in phase I/II studies for irinotecan and topotecan. Two other derivatives, 9-aminocamptothecin and GI 147211C, are undergoing phase I and early phase II evaluation. Although camptothecin is a plant extract, it and most of its derivatives are not affected by the classic P-gpMDR1 mechanism of resistance which may allow the development of novel combination chemotherapeutic regimens. Important areas of future endeavour will include the development of rational combination regimens and the pursuit of randomised trials. Based on single agent data, colorectal cancer and non-small-cell lung cancer should be the focus for future irinotecan studies. Small-cell lung cancer and ovarian carcinoma are logical tumour types to pursue with topotecan. Both 9-aminocamptothecin and GI 147211C are too early in their clinical evaluation to make recommendations about their future roles. Finally, the unfolding story of camptothecin analogue development will give important insights into the predictive value of preclinical observations on relative efficacy, schedule dependency, combination strategies and resistance mechanisms which have helped determine the strategies for clinical evaluation of these agents.

Antineoplastic Agents, Phytogenic↗

PubMed1996

Prospective comparison of the sclerosing agents doxycycline and bleomycin for the primary management of malignant pericardial effusion and cardiac tamponade.

PURPOSE: To compare the clinical efficacy and toxicity of doxycycline and bleomycin as sclerosing agents in the primary management of malignant pericardial effusion (MPE). METHODS: Twenty-seven consecutive adult patients referred to a tertiary-care institution for the management of cardiac tamponade and malignancy underwent pericardial drainage through a percutaneously placed pigtail catheter. They were then alternately assigned to undergo bleomycin or doxycycline pericardial sclerosis. RESULTS: There were 13 men and 14 women, with a median age of 59 years. They mainly had lung (70%) and breast cancers (11%), and all had clinical and echocardiographic evidence of cardiac tamponade. Although all patients had successfully placed catheters, six were inadvertently dislodged before sclerosis; 11 underwent bleomycin sclerosis and 10 doxycycline sclerosis. Twenty patients (one early death) were assessable. One patient in each group failed to respond to sclerosis with the initial agent, but both were sclerosed successfully with the other agent. Sclerosis was achieved with a median of two instillations for each agent and total median doses of bleomycin 20 mg and doxycycline 1,250 mg. Seventy percent of doxycycline patients developed significant retrosternal pain, compared with no bleomycin patients (P = .04). Doxycycline patients required a median of 3.5 more days of hospitalization (8.5 v 5) and 2 more days of pericardial catheterization (7 v 5) compared with bleomycin patients. Tamponade recurred in one bleomycin patient at 253 days, and in no doxycycline patient. CONCLUSION: Although bleomycin and doxycycline are equally effective sclerosing agents, bleomycin is associated with significantly less morbidity and should be the first-line chemical sclerosing agent for malignant pericardial effusions.

Adult↗

PubMed1996

Health-related quality-of-life studies of the National Cancer Institute of Canada Clinical Trials Group.

Since 1989, the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) has been successful in implementing and completing health-related quality-of-life (HQL) assessments as part of phase III clinical trials. Compliance rates for completing HQL instruments remain high, with a minimal amount of missing data. It is believed that this success is attributable not only to the high degree of commitment to measuring HQL by clinical trials investigators, nurses, data managers, and central office administrative staff, but also to the educational process that was instituted after the development of a CTG policy for measuring HQL. From inception to May 1995, a total of 27 clinical trials with HQL assessment have been initiated or completed. In the majority of trials, the core HQL instrument is the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). In addition to answering specific questions about HQL in these clinical trials, the trials provide the opportunity to do research into the measurement of HQL. Thus, current clinical trials include research questions about the appropriate timing of assessments, the reliability and validity of the QLQ-C30 and other instruments, the role of HQL data in assessing toxicity, and the significance of the results of HQL assessments. It is anticipated that this activity not only will be a rich source of information about the effects of cancer and its treatment on HQL but also will lead to improvements in measuring HQL in oncology.

Canada↗

PubMed1995

The role of vindesine in oncology--recommendations after 10 years' experience.

Vindesine, a vinca alkaloid derived from vinblastine, has been examined for activity against a variety of solid and hematological malignancies. Single-agent response rates average 18% in non-small cell lung cancer and it has been widely used in combination with cisplatin as first-line therapy for this disease. It has limited activity in breast cancer (average 16% response rate) and does not appear to improve outcome when combined with anthracyclines. Vindesine is frequently incorporated into combination regimens for the treatment of malignant melanoma, and head and neck cancer, although its single-agent activity in these diseases is modest (average 14 and 12% response rates, respectively). Its activity in the hematological malignancies appears to be greater and it has an important role in the treatment of acute lymphoblastic leukemia, particularly in children. It is currently being examined for its potential to synergize with the interferons and for its value as prolonged therapy in preventing metastasis.

Antineoplastic Agents, Phytogenic↗

PubMed1987