Assessing quality of life in clinical trials.
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Clinical Trials as Topic↗
Biomedical subjects
J Pater
Publications and source records attributed to J Pater.
The restaging of responding patients with limited small cell lung cancer. Is it really useful?
A retrospective review of data on patients entered on two limited small cell lung cancer studies of the National Cancer Institute of Canada (BR.3 and BR.6) was undertaken to determine the value of restaging and rebronchoscopy in responding patients. An economic evaluation was also done. Repeat scans (brain, liver) and bronchoscopy were carried out in 190 patients and 5 (2.6 percent) were positive, despite other evidence suggesting response. One hundred thirty-nine of 324 patients who achieved complete response on the two trials underwent rebronchoscopy. Among these, 122 (87.7 percent) were negative and eight (5.8 percent) were inconclusive. Nine (6.5 percent) were positive despite other evidence suggesting the patient had achieved a complete response. A small group of nine patients with positive rebronchoscopy survived for a shorter time than the group with negative or inconclusive rebronchoscopies. The survival difference was only statistically significant when analyzed using the log rank test, but it was not significant when analyzed by the Wilcoxon test. The economic analysis showed that it costs $11,333 per patient reclassified when scans were redone in these patients. The cost could even have been higher had we used present-day scanning techniques (computed tomography and magnetic resonance imaging), although they might be slightly more sensitive. The cost of rebronchoscopy per patient reclassified was $14,960. Therefore, we recommend that restaging (scans or rebronchoscopy) not be done in responding patients with limited small cell lung cancer, thus potentially saving health care dollars as well as reducing patient inconvenience with no detrimental effect on survival.
Bronchoscopy↗
Allotolerance induced by intrathymic application of alloantigen: introduction of a new and clinically relevant procedure allowing heart graft survival in high-responder rats.
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Animals↗
Quality-of-life assessment: patient compliance with questionnaire completion.
BACKGROUND: Previous investigators have found that compliance with quality-of-life data collection on cancer clinical trials is poor. There is general belief that collecting complete quality-of-life data is at present an unachievable goal. PURPOSE: We assessed the completeness of quality-of-life data collection on trials instituted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG), since incorporation of quality-of-life outcomes into trials became mandatory for the group. METHODS: Data from three NCIC CTG trials in which quality of life was a study end point were examined to determine the extent to which protocol specifications were met with respect to questionnaire completion. Two of the studies examined adjuvant therapies, and one examined anti-emetics. In two trials, the quality-of-life questionnaire of the European Organization for Research and Treatment of Cancer was used; in the other, the Breast Cancer Chemotherapy Questionnaire. RESULTS: Patient compliance with questionnaire completion was unexpectedly high: More than 95% of the scheduled questionnaires were returned, and more than 99% of the questions were answered. CONCLUSIONS: We attribute this success to a comprehensive set of measures taken to enhance compliance on these studies. Which of these measures was most contributory requires further investigation, as does the issue of whether similar results can be obtained in other circumstances. IMPLICATIONS: It seems that the commonly held belief that quality-of-life data cannot be successfully collected in multicenter cancer trials is incorrect.
Clinical Trials as Topic↗
A randomised, double-blind comparison of granisetron with high-dose metoclopramide, dexamethasone and diphenhydramine for cisplatin-induced emesis. An NCI Canada Clinical Trials Group Phase III Trial.
151 patients (149 evaluable) receiving their first course of chemotherapy containing cisplatin in a dose of at least 50 mg/m2 were randomised to receive either a single dose of intravenous granisetron 80 micrograms/kg or intravenous metoclopramide 2 mg/kg every 2 h for five doses plus a single dose of dexamethasone 10 mg and diphenhydramine. After 24 h, there was no significant difference between groups with respect to nausea or vomiting: in the granisetron group 46% of patients had no emesis, versus 44% of the standard group. Granisetron is an antiemetic agent with efficacy similar to that of high-dose metoclopramide plus dexamethasone.
Antiemetics↗
Systemic infusion versus bolus chemotherapy with 5-fluorouracil in measurable metastatic colorectal cancer.
From January 31, 1986 to January 31, 1989, 184 eligible patients were enrolled in a randomized study of either infusional or bolus 5-fluorouracil (5-FU) for the treatment of metastatic measurable colorectal cancer. Infusion was administered at an escalated dose schedule starting at 350 mg/m2 per day for 2 weeks with a 2-week rest period on a monthly basis, while bolus 5-FU was started at 400-450 mg/m2 for 5 days every 28 days. In these chemotherapy-naive patients with good performance status, the infusion arm produced a response in 11 of 88 patients versus 6 of 82 in the bolus arm (p = 0.384). Progression free survival was significantly longer (p = 0.0139) in the infusion group (3.8 versus 2.3 months), but no significant difference in survival was observed (p = 0.207). As expected, the toxicities of the regimens were different in character, but each had approximately a 20% incidence of significant toxicities. Neither of these methods of administering fluorouracil results in an exceptional response rate, nor does the infusion have an impact on survival as compared to the bolus route. If this type of complicated infusional approach is to continue, especially with increasing dosage (which could be accomplished on our schedule), randomized studies with survival as an endpoint must remain the gold standard.
Adult↗
A phase II study of menogaril in low-grade non-Hodgkin's lymphoma. An NCI Canada Clinical Trials Group study.
The NCI Canada Clinical Trials Group conducted a phase II study of menogaril given intravenously every 4 weeks in low-grade non-Hodgkin's lymphoma. Fifteen of 26 eligible patients had had no prior therapy. Partial responses were seen in 9 patients (35%). Toxicity was moderate including myelosuppression, nausea, phlebitis, alopecia, and lethargy. This drug has only modest activity in this potentially responsive group of patients.
Antineoplastic Agents↗
A randomized, double-blinded study comparing six doses of batanopride (BMY-25801) with methylprednisolone in patients receiving moderately emetogenic chemotherapy.
Several agents in a new class of antiemetic compounds, 5-hydroxytryptamine (5-HT3) antagonists, have shown promise as effective antiemetics with fewer side effects than metoclopramide. One of these agents, batanopride, produced no severe toxicity at doses that prevented emesis due to chemotherapy in early Phase I trials. We conducted a randomized, double-blinded, 7 arm clinical trial to: (1) identify the presence of a dose-response for complete protection from emesis, and (2) compare batanopride with a standard antiemetic, methylprednisolone if a dose-response was found not to exist. Prior to chemotherapy, six patient groups each received a single intravenous dose of batanopride ranging from 0.2 to 6.0 mg/kg whereas a seventh group received methylprednisolone 250 mg intravenously. Chemotherapy-naïve cancer patients scheduled to receive moderately emetogenic chemotherapy were eligible. Primary treatment outcomes that were recorded and analyzed included the number of episodes of emesis, the time to the first episode of emesis as well as the frequency and severity of nausea. Two hundred and eight patients accrued between April 1989 and February 1990 were evaluable for response. A significant dose-response effect for complete protection from emesis was not seen over the first 24 hours after chemotherapy (p = 0.102). However, a linear dose-response effect for time to first emesis was evident in a multivariate analysis (p = 0.029). While the highest batanopride dose group was associated with a higher complete protection rate (CPR) than the control group, this group also exhibited a higher incidence of diarrhea (p = 0.013), hypotension, and electrocardiographic abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Effect of daily etidronate on the osteolysis of multiple myeloma.
Progressive bone disease in multiple myeloma frequently leads to osteolysis, bone resorption, pathologic fractures, vertebral compression, and hypercalcemia. We conducted a double-blind study in 173 newly diagnosed multiple myeloma patients of etidronate disodium (EHDP), a diphosphonate compound that reduces bone resorption by inhibiting osteoclastic activity. The patients were randomly assigned to receive oral EHDP 5 mg/kg/d or placebo until death or discontinuation due to intolerance or refusal. The extent of vertebral deformity was measured by a vertebral index as well as height. The frequency of pathologic fractures, hypercalcemia, and bone pain was regularly assessed, as well as size and number of osteolytic lesions. All patients received melphalan and prednisone daily for 4 days every 4 weeks as the primary chemotherapy for their disease. Although the repeated measures analysis showed a significant height loss, there was no difference between treatment arms (P = .98). There was no significant difference in bone pain, episodes of hypercalcemia, or development of pathologic fractures. Patients on EHDP showed less deterioration in their vertebral index, but this difference only approached statistical significance (P = .07). We conclude that EHDP therapy used in this dosage schedule does not have a clinically significant impact in multiple myeloma.
Aged↗
Counting the costs of chemotherapy in a National Cancer Institute of Canada randomized trial in nonsmall-cell lung cancer.
An economic evaluation was undertaken of a previously reported National Cancer Institute of Canada (NCIC) trial of chemotherapy in advanced nonsmall-cell lung cancer (NSCLC). That trial had demonstrated a survival benefit associated with the use of either vindesine and cisplatin (VP) or cyclosphosphamide, doxorubicin, and cisplatin (CAP) in relation to best supportive care (BSC). The economic technique used in this evaluation was cost-effectiveness analysis (CEA). All costs were determined from the viewpoint of two provincial health care plans. When compared with BSC, the survival benefit of 8 weeks in favor of patients receiving CAP chemotherapy was associated with an economic saving of $949.49 (in 1984 Canadian dollars). This translated into a savings of $6,171.69 per year of life gained. The mean survival benefit of 12.8 weeks that was obtained with VP chemotherapy compared with BSC was associated with an increased cost of $3,637.60 per patient, or $14,777.75 per year of life gained. The economic evaluation demonstrated that the majority of costs on each of the three treatment arms was related to hospitalization and not to the use of chemotherapy agents. These results compare favorably with estimates of cost-effectiveness (CE) of commonly used treatments for other diseases and demonstrate that a policy of supportive care is associated with costs that may exceed those of active treatment. It is concluded that economic factors should not adversely affect decisions regarding the use of chemotherapy in advanced NSCLC.
Antineoplastic Combined Chemotherapy Protocols↗
[Structure of the needs of former prisoners of the Nazi concentration camps].
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Concentration Camps↗
[The concept of values in former prisoners of Nazi concentration camps].
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Aged↗
Cost-effectiveness of cancer chemotherapy: an economic evaluation of a randomized trial in small-cell lung cancer.
An economic evaluation of a randomized trial of cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and vincristine alone or alternating with etoposide (VP-16) and cisplatin in extensive small-cell lung cancer (SCLC) was undertaken. A survival benefit of 1.6 months in favor of alternating chemotherapy was associated with an additional cost of $450 (1984 Canadian dollars) per patient. This translated to a cost of $3,370 per year of life gained. Sensitivity analyses demonstrated that the cost-effectiveness (CEA) of alternating chemotherapy was greatest when treatment was given on an outpatient basis. The results of the evaluation were sensitive to hospitalization rates, but even the most unfavorable analyses revealed the CEA of alternating chemotherapy to be comparable to that of treatments of common nonmalignant diseases. It is concluded that the CEA of alternating chemotherapy for SCLC was favorable when compared with accepted treatments for nonmalignant diseases. The survival benefit seen with alternating chemotherapy was felt to be clinically significant and alternating chemotherapy is recommended as routine therapy for extensive SCLC.
Antineoplastic Combined Chemotherapy Protocols↗
The use of VP-16 plus cisplatin during induction chemotherapy for small-cell lung cancer.
In an attempt to circumvent innate or acquired tumor-cell resistance to chemotherapy, patients with small-cell lung cancer (SCLC) were treated with induction therapy that incorporated two active and potentially non-cross-resistant chemotherapy regimens on two National Cancer Institute of Canada (NCI-C) trials. Patients with limited disease (LD) SCLC were treated with cyclophosphamide, doxorubicin (Adriamycin [Adria Laboratories, Columbus, Ohio]) and vincristine (CAV) and VP-16 plus cisplatin in two different sequences. One arm was randomized to receive CAV alternating with VP-16 plus cisplatin for a total of six treatment cycles, and the other arm received three courses of CAV followed by three courses of VP-16 plus cisplatin. Both treatment strategies produced similar response rates and survival curves, and each treatment group has a projected 2-year survival of 20%. Patients with extensive disease (ED) were treated with either six cycles of CAV (standard regimen) or CAV alternating with VP-16 plus cisplatin for a total of six treatment cycles. In this study, the alternating regimen produced a higher complete response (CR) rate (40% v 27%) and overall response rate (61% v 39%; P less than .01). The progression-free survival was also superior for the alternating arm (P = .001), as was overall survival (P less than .05). The frequency of thrombocytopenia and severe gastrointestinal toxicity was slightly greater in the alternating arm, but the frequency of neutropenia and infection was less. The alternation of CAV and VP-16 plus cisplatin during induction therapy is an effective treatment strategy in the management of SCLC and superior to CAV alone in extensive SCLC.
Antineoplastic Combined Chemotherapy Protocols↗
Phase II study of acivicin in non-small cell lung cancer: a National Cancer Institute of Canada Study.
Thirty-six previously untreated patients with metastatic non-small cell lung cancer received acivicin at a starting dose of 15 mg/m2, given over 5 days and repeated every 21 days. Hematological toxicity was dose-related; one patient died of neutropenic sepsis at 18 mg/m2. Nonhematological toxicity was mild, with gastrointestinal symptoms being the most prominent. Neurological toxicity was seen in 48% of the patients and consisted of confusion, hallucinations, and sleeping difficulty. A minority of patients required dose reduction because of these symptoms. In 33 evaluable patients, two partial remissions were documented, with seven additional patients showing evidence of minor responses. Although modest, these responses warrant further study of acivicin in non-small cell lung cancer in combination with other agents.
Adult↗
A multicenter comparative trial of tobramycin and ticarcillin vs moxalactam and ticarcillin in febrile neutropenic patients.
During a multicenter prospective randomized trial in febrile neutropenic patients (neutrophil count, less than 1,000/cu mm), 103 episodes were treated with tobramycin sulfate plus ticarcillin disodium (TT) while 117 were treated with moxalactam plus ticarcillin disodium (MT). The majority of patients had an underlying diagnosis of leukemia (60%) and most (62.8%) had granulocyte counts of less than 100/cu mm at the start of therapy. The response rates for clinically or microbiologically documented episodes were 38 of 60 (55.1%) for TT and 38 of 64 (59.4%) for MT. The MT regimen appeared to be more effective for gram-positive infections (56% vs 33%) while TT appeared more effective for gram-negative infections (64% vs 40%). Nephrotoxicity attributable to study drugs occurred in only 2.3% of cases (one on each treatment arm). Prolongation of the prothrombin time was observed in only six of 78 (7.7%) in the TT arm as compared with 39 of 103 (38%) in the MT arm. Neither regimen was adequate for the unusually high frequency of gram-positive pathogens seen during this study.
Adolescent↗
Survey of surgical management of malignant melanoma in Canada: optimal margins of excision and lymph-node dissection.
The feasibility of clinical trials involving the surgical management of primary melanoma was assessed through a survey of Canadian surgeons who treat this disease. Surgeons were polled as to their current practice regarding node dissection and margins of resection of the primary lesion. Their interest in randomized trials addressing these practices was also assessed. Two hundred and forty questionnaires were distributed to 20 centres across Canada. The total number of patients with melanoma seen annually by the 131 surgeons who responded was 790 - of the approximately 1000 new cases of melanoma diagnosed in Canada each year. Of responding surgeons, 63% currently perform wide excision (taking 3 to 5 cm of normal tissue) for lesions less than 1.5 mm in depth and 37% perform limited excision (including 1 to 2 cm of normal tissue). Of all surgeons responding, 76% were interested in a randomized trial comparing wide and limited excision in these superficial lesions. Currently, 90% of surgeons perform wide excision of lesions 1.5 mm or more in depth and 10% perform limited excision. Fifty-nine percent were interested in a randomized trial comparing wide and limited excision in these deeper lesions. Twenty-four percent of surgeons routinely perform prophylactic node dissection on all patients with lesions 1.5 mm or more in depth; 66% wait until there is clinical suspicion of nodal metastases and 9% follow some other policy. The results of this survey indicate that (a) surgical management is varied, (b) radical surgery remains common practice and (c) surgeons are interested in randomized trials that will determine optimal treatment.
Canada↗
Studies of human natural killer cells. III. Neutropenia associated with unusual characteristics of antibody-dependent and natural killer cell-mediated cytotoxicity.
A 52-year-old Caucasian man with chronic neutropenia and recurrent infections was found to have an increased proportion of peripheral T lymphocytes having Fc receptors for IgG (T gamma ). Although levels of antibody-dependent cell-mediated cytotoxicity (ADCC) and "natural" killing (NK) by unfractionated lymphocytes were similar to those of a control donor, the frequency of KN cells was markedly increased. Removal of E rosette-forming cells eliminated both NK and ADCC by the patient's peripheral blood, in marked contrast to the enhanced cytotoxicity seen with control lymphocytes. Both normal and patient ADCC and NK functions were removed by depletion of Fc receptor-bearing cells. These depletion experiments proved that all of the patient's killer cells were E rosette-forming T gamma cells, in contrast to the heterogeneous pattern of null gamma and T gamma killer cells seen in the blood of normal donors. The homogeneity of the T gamma proliferation suggested that ADCC and NK were mediated by the same cell type, albeit acting by different mechanisms. The addition of the patient's serum and lymphocytes to chromium-labelled normal granulocytes caused a low but significant level of cytotoxicity, indicating that the patient's neutropenia may have been caused by a similar mechanism in vivo. There was no evidence of complement-dependent serum antibody-mediated neutrophil lysis, but one serum sample taken over the course of the patient's disease agglutinated granulocytes from four of five donors tested.
Agglutination↗