Biomedical subjects

B Zee

Publications and source records attributed to B Zee.

At least 55 records · Page 3Linked to original sources

PubMed1997

Fatigue in patients with cancer: results with National Cancer Institute of Canada Clinical Trials Group studies employing the EORTC QLQ-C30.

The purpose of this study was to examine the factors which affect the level of fatigue among patients participating in clinical trials in which this symptom had been assessed with the EORTC QLQ-C30. Data were assembled from 2390 patients in ten clinical trials in which the QLQ-C30 had been used to assess baseline and on-study quality of life. The relationship between the level of fatigue reported by the patients on the fatigue scale of this questionnaire and patient and disease characteristics was assessed in univariate and multivariate cross-sectional analyses. In addition, changes in fatigue scores were compared in a longitudinal analysis among patients on two arms of an anti-emetic trial whose emesis control was markedly different. Baseline fatigue levels differed substantially among patients taking part in the different trials. Factors associated with greater fatigue severity on univariate analysis included: female gender, presence of metastatic disease, and poorer performance status. In addition, on multivariate analyses the oldest patients were found to have less fatigue, as were patients with breast cancer, while patients with ovarian and lung cancer experienced greater fatigue. Patients on the arm of the anti-emetic trial in which emesis was better controlled showed significantly less increase in fatigue after receiving chemotherapy. The fatigue scale of the QLQ-C30 appears to provide a useful approach to assessing this important symptom. The relationships found between fatigue and patient and disease characteristics need further exploration as does the degree to which the QLQ-C30 fully captures this dimension of quality of life.

Adult↗

PubMed1997

Mammographic density in women on postmenopausal hormone replacement therapy.

BACKGROUND: Studies have suggested that mammographic density and pattern are affected by hormone replacement therapy (HRT) and may influence breast diagnosis. Because 40% of breast cancers diagnosed at our center are mammographically detected while still clinically occult, mammographic sensitivity is crucial. For this reason we studied the effect of HRT on mammographic density. METHODS: During a period of 18 months we studied consecutive women older than 54 years attending for breast screening. We recorded HRT use and dosing regimes. A breast density score (BDS) was developed and applied to all mammograms. RESULTS: Mammograms of 148 HRT users were compared with those of 158 nonusers. HRT users had a significantly higher mean density score (4.7 versus 3.4; p < 0.001). Only 11% of non-HRT users had high scores compared with 37% among HRT users (p < 0.001). The significant difference remained when women were stratified by age. Duration of HRT (longer or shorter than 5 years) did not affect density scores. CONCLUSIONS: HRT is associated with a significant increase in breast density. In turn, density and mammographic sensitivity are related. The possibility that increased breast density will hamper mammographic diagnosis of clinically occult cancers is worrisome.

Age Factors↗

PubMed1997

Macromolecular interstitial clearance, tumour vascularity, other prognostic factors and breast cancer survival.

BACKGROUND: Clearance of large molecules from the interstitial space is an important function of lymphatics and is affected by local pathologic changes. OBJECTIVE: To determine if the clearance rate of interstitially injected albumin is correlated to tumour characteristics and outcome in women with invasive breast cancer. METHOD: In a consecutive series of women coming to biopsy for suspected breast cancer, technetium-tagged albumin was injected into the tissue adjacent to the palpable mass. The isotope disappearance rate was measured over two hours. Also assessed were the maximum vessel density (MVD-using Factor VIII polyclonal antisera), the proliferation rate (using Ki-67 antisera), node status, tumour size, histologic and nuclear grade, mitotic rate, and p53 and c-erbB-2 oncoproteins. All patients were followed until relapse and for a minimum of 10 years. RESULTS: In multivariate analysis, an association between relapse-free survival and isotope clearance rate was suggested (p = 0.024). The best outcome was seen in patients with the least isotope clearance. Node status, size, histologic and nuclear grade, and mitotic rate correlated with survival. MVD did not correlate with survival and was inversely related to the isotope clearance rate. Tumour proliferation rate, and the c-erbB-2 and p53 oncoproteins did not relate to outcome. CONCLUSION: The role of lymphatics in breast cancer is difficult to study. Measurement of interstitial clearance may be a useful technique and could be a prognostic factor.

Aged↗

PubMed1997

The role of the 5-HT3 antagonists ondansetron and dolasetron in the control of delayed onset nausea and vomiting in patients receiving moderately emetogenic chemotherapy.

BACKGROUND: 5-HT3 antagonists are effective in reducing the acute nausea and vomiting caused by cancer chemotherapy. However, it is not clear whether continuing these agents beyond twenty four hours is useful in controlling emesis on days two to seven after chemotherapy. PATIENTS AND METHODS: Four hundred seven patients receiving moderately emetogenic chemotherapy who had been given dexamethasone 8 mg i.v. and either ondansetron 32 mg i.v. or dolasetron 2.4 mg/kg i.v. were randomized to continue either an oral form of their 5-HT3 antagonist (ondansetron 8 mg b.i.d. or dolasetron 200 mg daily) plus dexamethasone 8 mg p.o. daily or dexamethasone alone for days two to seven. Endpoints assessed by self-report were: 1) complete control (no vomiting, no rescue medications, no missing data) of emesis; 2) nausea severity; and 3) quality-of-life as measured by the EORTC QLQ-C30. RESULTS: Continuation of 5-HT3 antagonists improved slightly, but not significantly, the complete control rate (47% vs. 41%: P = 0.24 one-sided) after chemotherapy. However, mean nausea severity was significantly (P = 0.015 one sided) reduced (by 3 mm on a 10 cm scale) on the combined arm. Minimal differences in quality of life were observed. CONCLUSION: The benefit of continuing 5-HT3 antagonists beyond 24 hours is modest and the merits of routine use in these circumstances debatable.

Antiemetics↗

PubMed1997

Modification of the EORTC QLQ-C30 (version 2.0) based on content validity and reliability testing in large samples of patients with cancer. The Study Group on Quality of Life of the EORTC and the Symptom Control and Quality of Life Committees of the NCI of Canada Clinical Trials Group.

A revision of the Quality of Life Questionnaire (QLQ-C30) of the European Organization for Research and Treatment of Cancer (EORTC) was undertaken to improve low internal consistency estimates (Cronbach's alpha) and content validity for the role functioning scale and a conceptual difficulty (undue emphasis on physical functioning) in the global quality of life (QOL) scale. The role functioning items were reworded and a four-category response format was substituted for the previous dichotomous format. A new item asking about 'overall health' was substituted for the 'overall physical condition' item in the global QOL domain. The original and new versions were tested at three time points in a total of 1,181 patients with cancer in Canada (n = 696) and the Netherlands (n = 485). In both samples there was a marked improvement in internal consistency for the role functioning scale (Cronbach's alpha s ranging from 0.78-0.88) in the new version. In the global QOL scale, the substitution of the new item for the previous one did not alter internal consistency (Cronbach's alpha's ranging from 0.81-0.92). The revised versions of the role functioning and global QOL domains have been incorporated into the QLQ-C30 (version 2.0).

Adult↗

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↗

PubMed1997

Determinants of postchemotherapy nausea and vomiting in patients with cancer. Quality of Life and Symptom Control Committees of the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To assess whether prechemotherapy health-related quality-of-life (HQL) variables are associated with postchemotherapy nausea and vomiting (PCNV), and to determine their relationship to patient and treatment variables. PATIENTS AND METHODS: Eight hundred thirty-two chemotherapy-naive patients scheduled to receive antiemetic regimens containing a 5-hydroxytryptamine (5-HT3) antagonist with or without dexamethasone for moderately or highly emetogenic chemotherapy were enrolled. HQL was measured by the self-report European Organization for Research and Treatment of Cancer (EORTC) Care Quality of Life Questionnaire (QLQ-C30) within 7 days before chemotherapy. Prechemotherapy HQL scores, as well as other patient, disease, and treatment variables were compared in the groups of patients who had PCNV and those who did not have PCNV. All variables were assessed initially in a univariate analysis and then together in a multivariate analysis using step-wise logistic regression. The final model generated by the multivariate analyses was used in a risk factor analysis to predict PCNV. RESULTS: Univariate analyses identified 10 HQL variables and five patient and treatment characteristics that were associated with PCNV. In the multivariate analysis, the variables remaining in the final model included low social functioning, prechemotherapy nausea, female gender, highly emetogenic chemotherapy, and the lack of maintenance antiemetics (5-HT3 antagonists with or without dexamethasone) after chemotherapy. A history of low alcohol use was also associated with PCV, whereas increased fatigue and lower performance status were associated with PCN. In the risk factor analysis, the incidence of PCV increased from 20% in those having no risk factors to 76% in those having any four of the six risk factors. CONCLUSION: Several pretreatment HQL, patient, and treatment characteristics are associated with the occurrence of PCNV. Patients about to receive moderately or highly emetogenic chemotherapy should be screened for these factors and additional measures, such as behavior modification and modification of antiemetic therapy, should be considered in attempts to improve the control of PCNV.

Analysis of Variance↗

PubMed1997

Treatment of advanced Hodgkin's disease with chemotherapy--comparison of MOPP/ABV hybrid regimen with alternating courses of MOPP and ABVD: a report from the National Cancer Institute of Canada clinical trials group.

PURPOSE: This randomized, prospective trial compares outcomes for patients with advanced Hodgkin's disease treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/doxorubicin, bleomycin, and vinblastine (ABV) hybrid regimen or alternating MOPP/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). METHODS: Three hundred one patients with advanced Hodgkin's disease were randomized to receive MOPP/ ABV hybrid regimen or alternating MOPP/ABVD after stratification for prior treatment, B symptoms, and treatment center. Eligible patients were either previously untreated and found to have stage IIIB, IVA, or IVB disease or previously treated with wide-field irradiation. Responding patients received a minimum of eight cycles of chemotherapy. Those with residual disease in a localized region received irradiation between the sixth and seventh cycle of treatment. RESULTS: Response rates to the two regimens were similar. Five-year overall survival rates were 81% and 83% for MOPP/ABV hybrid and alternating MOPP/ ABVD, respectively (P = .74; 95% confidence interval [CI] for the difference, -11% to 7%). Five-year failure-free survivals were 71% and 67% for MOPP/ABV hybrid and alternating MOPP/ABVD, respectively (P = .87; 95% CI for the difference, -9% to 17%). Significantly more episodes of febrile neutropenia and stomatitis were observed with the MOPP/ABV hybrid regimen; there was no significant difference in fatal toxicity. Patients with predefined, high-quality partial responses (PR-1s) had results similar to those with complete responses (CRs). Planned subset analysis showed no significant difference in outcome between the two arms of the trial for patients with newly diagnosed disease (5-year failure-free survival rates were 70% for MOPP/ABV hybrid and 59% for alternating MOPP/ABVD; P = .180), but superiority of alternating MOPP/ABVD for patients with prior irradiation (5-year failure-free survival 94% v 73%; P = .017). CONCLUSION: MOPP/ABV hybrid and alternating MOPP/ABVD regimens are equally effective for patients with advanced Hodgkin's disease.

Actuarial Analysis↗

PubMed1997

Randomized trial of cyclophosphamide, methotrexate, and fluorouracil chemotherapy added to tamoxifen as adjuvant therapy in postmenopausal women with node-positive estrogen and/or progesterone receptor-positive breast cancer: a report of the National Cancer Institute of Canada Clinical Trials Group. Breast Cancer Site Group.

PURPOSE AND METHODS: By the mid 1980s, tamoxifen alone was considered standard adjuvant therapy for postmenopausal women with node-positive, estrogen receptor (ER)- or progesterone receptor (PgR)-positive breast cancer. From 1984 through 1990, 705 eligible postmenopausal women with node-positive, ER- or PgR-positive breast cancer were randomized to a National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) study that compared tamoxifen 30 mg by mouth daily for 2 years (TAM) versus TAM plus chemotherapy with all-intravenous cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, and fluorouracil 600 mg/m2 given every 21 days for eight cycles (CMF). RESULTS: There were no significant differences in overall survival, recurrence-free survival, locoregional recurrence-free survival, or distant recurrence-free survival between the two treatment arms. However, there was significantly greater severe toxicity, which included leukopenia (P < .0001), nausea and vomiting (P < .0001), and thromboembolic events (P < .0001), as well as significantly more mild or greater toxicity, which included thrombocytopenia (P = .04), anemia (P = .02), infection (P = .0004), mucositis (P = .0001), diarrhea (P = .0001), and neurologic toxicity (P = .006), in women who received TAM plus CMF. CONCLUSION: The addition of CMF to TAM adds no benefit and considerable toxicity in this group of women.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Phase III double-blind comparison of dolasetron mesylate and ondansetron and an evaluation of the additive role of dexamethasone in the prevention of acute and delayed nausea and vomiting due to moderately emetogenic chemotherapy.

PURPOSE: To compare the efficacy of dolasetron and ondansetron in controlling nausea and vomiting in the first 24 hours; to evaluate the efficacy when dexamethasone is added to either drug in the first 24 hours; and to extend these comparisons over 7 days in patients receiving moderately emetogenic chemotherapy. PATIENTS AND METHODS: This was a multicenter, double-blind, randomized study with six parallel arms that used a 2 x 2 factorial design in chemotherapy-naive patients. In arm 1, dolasetron (2.4 mg/kg) was given intravenously (I.V.) prechemotherapy, followed 24 hours later by oral dolasetron (200 mg once daily) for 6 days. Arms 2 and 3 consisted of dolasetron and dexamethasone 8 mg I.V., followed 24 hours later by oral dexamethasone (8 mg once daily) in one arm, and oral dexamethasone and dolasetron in the other, also for 6 days. In arms 4, 5, and 6, ondansetron (32 mg I.V. or 8 mg orally twice daily) was administered in a similar manner to arms 1, 2, and 3 before and 24 hours after chemotherapy. Mean nausea severity (MNS) was assessed on a visual analog scale (VAS) in a daily diary. RESULTS: Of 703 patients enrolled, 696 were eligible. There were 343 dolasetron- and 353 ondansetron-treated patients; 57% of dolasetron-treated patients had complete protection in the first 24 hours versus 67% of patients who received ondansetron (P = .013). MNS was also more pronounced on the dolasetron arm (P = .051). Sixty-seven percent of patients who received added dexamethasone in the first 24 hours had complete protection, compared with 55% without dexamethasone (P < .001). MNS was significantly reduced with the addition of dexamethasone (P < .001). At 7 days, dolasetron and ondansetron had equivalent complete protection rates (36% and 39%, respectively). With the addition of dexamethasone, 48% of patients compared with 28% had complete protection (P < .001). MNS was significantly improved with added dexamethasone (P < .001). CONCLUSION: At the doses used, dolasetron was significantly less effective than ondansetron at controlling nausea and vomiting in the first 24 hours in patients receiving moderately emetogenic chemotherapy, but there was no demonstrable difference between both drugs over 7 days. The addition of dexamethasone significantly improved the efficacy of both drugs in the first 24 hours and over 7 days.

Administration, Oral↗

PubMed1996

Quinolone-based antibacterial chemoprophylaxis in neutropenic patients: effect of augmented gram-positive activity on infectious morbidity. National Cancer Institute of Canada Clinical Trials Group.

OBJECTIVE: To determine whether augmented quinolone-based antibacterial prophylaxis in neutropenic patients with cancer reduces infections caused by gram-positive cocci and preserves the protective effect against aerobic gram-negative bacilli. DESIGN: Open, randomized, controlled, multicenter clinical trial. SETTING: Centers participating in the National Cancer Institute of Canada Clinical Trials Group. PATIENTS: 111 eligible and evaluable patients hospitalized for severe neutropenia (neutrophil count < 0.5 x 10(9)/L lasting at least 14 days) who were receiving cytotoxic therapy for acute leukemia or bone marrow autografting. INTERVENTION: One of three oral antibacterial prophylactic regimens (norfloxacin, 400 mg every 12 hours; ofloxacin, 400 mg every 12 hours; or ofloxacin, 400 mg, plus rifampin, 300 mg every 12 hours) beginning with cytotoxic therapy. MEASUREMENTS: Incidence and cause of suspected or proven infection. RESULTS: Microbiologically documented overall infection rates for norfloxacin, ofloxacin, and ofloxacin plus rifampin were 47%, 24%, and 9%, respectively (P < 0.001). Corresponding rates were 24%, 13%, and 3%, respectively for staphylococcal bacteremia (P = 0.03) and, 21%, 3%, and 3%, respectively for streptococcal bacteremia (P < 0.01). The pattern of bacteremia suggested that rifampin played a role in suppressing staphylococcal infection. Both ofloxacin alone and ofloxacin plus rifampin had a clinically significant antistreptococcal effect. Aerobic gram-negative rods were cleared from rectal surveillance cultures in all patients after a median of 5.5 days and caused infection in only one patient (0.9%). The reductions in the number of microbiologically documented infections among ofloxacin recipients and ofloxacin plus rifampin recipients were offset by concomitant increases in the number of unexplained fevers (24% of norfloxacin recipients, 53% of ofloxacin recipients, and 49% of ofloxacin plus rifampin recipients; P = 0.02). No statistically significant difference was found among the treatment arms with respect to the overall incidence of febrile neutropenic episodes as defined for this trial (79% for the norfloxacin group, 82% for the ofloxacin group, and 77% for the ofloxacin plus rifampin group). CONCLUSIONS: Quinolone-based antibacterial chemoprophylaxis protected patients from aerobic gram-negative bacillary infections. Augmentation of the gram-positive activity reduced the incidence of gram-positive infections but did not influence the overall incidence of febrile neutropenic episodes.

Adult↗

PubMed1996

Thermography. Its relation to pathologic characteristics, vascularity, proliferation rate, and survival of patients with invasive ductal carcinoma of the breast.

BACKGROUND: The reason for the thermal abnormality associated with some breast cancers is unclear. We previously reported that a thermographic abnormality is associated with tumor size and lymph node involvement. Despite this association, we were unable to demonstrate an independent association between an abnormal thermogram and survival. METHODS: To expand our previous findings, we assessed patients undergoing liquid crystal (contact) thermography (LCT) to identify a basis for the thermal abnormality and its relationship to survival. We assessed 420 women with invasive ductal carcinoma (IDC) followed for a mean of 6.2 years. In a consecutive series of 181 patients from the overall group, vascularity was assessed using a Doppler ultrasound (US) and microvessel density (MVD) by immunohistochemical staining with Factor VIII-related antigen. The tumor proliferation rate was measured immunohistochemically using Ki-67 monoclonal antibody. RESULTS: An abnormal thermogram was found in 18.6% of patients with IDC. A significant association was demonstrated between an abnormal LCT and age, stage, lymph nodal status, size, grade, and estrogen receptor status. We found no association between a LCT abnormality and MVD or proliferation rate. There was a significant relationship with US-demonstrated vascularity. In multivariate analysis, we found that LCT abnormality was not an independent prognostic variable for either overall or disease free survival. CONCLUSIONS: An abnormal thermogram is associated with large tumor size, high grade, and lymph node positivity but not proliferation rate or MVD. It also may be associated with relatively large regional vessels that can be identified by US. However, thermography is not an independent prognostic indicator.

Age Factors↗

PubMed1996

Vascularity demonstrated by Doppler ultrasound and immunohistochemistry in invasive ductal carcinoma of the breast.

BACKGROUND: Vascularity is an important determinant of a tumour's ability to grow and disseminate. Breast tumour vascularity can be determined with doppler ultrasound (US) and by counting the vessels microscopically (microvascular density-MVD). The biologic characteristics of tumours based on their vascularity have not been extensively studied. METHOD: Preoperative US was performed on 207 patients with invasive ductal breast carcinomas (IDC). MVD was assessed immunohistochemically using polyclonal antisera against factor VIII and the proliferation rate was measured with Ki-67 polyclonal antisera. Histologic tumour characteristics and oestrogen receptor (ER) status were determined. Thermography was performed on 174 of the patients. RESULTS: Twenty-five percent of IDC demonstrated US-vascularity. US-vascular tumours were more likely to be node positive, and had a higher mitotic rate than avascular cancers. US-vascularity was more common in tumours with MVD greater than 80 vessels/250x field than those with fewer vessels. The proliferation rate, histologic grade III, and nuclear grade III were higher and ER positivity lower, but the differences were not statistically significant. US-vascular cancers were associated with significantly more thermographic abnormalities. The cancer recurrence rate at three years was higher in patients with vascular cancers although the difference was not statistically significant. CONCLUSION: US appears to be a simple, non-invasive method of identifying vascular cancers associated with factors indicating a poor prognosis.

Adult↗

PubMed1996

Validation of a 3D optoelectronic motion analysis system for the wrist joint.

OBJECTIVE: A study was undertaken to determine the experimental accuracy of a non-invasive optoelectonic 3-dimensional tracking system in assessing wrist joint motion. DESIGN: This was an in vivo experimental study involving volunteer subjects performing prescribed wrist motions. BACKGROUND: Current clinical practice does not include routine kinematic analysis for evaluating arthritic disease state, although motion disorders are common. METHODS: Surface markers were applied to 24 subjects assigned two hand postures in a test-retest factorial design for the expected range of motion. The marker positions were measured optoelectronically and using calibrated stereoradiography, to determine the positions of the surface markers and of key bone landmarks. Alignment and motion were compared for the three measurement techniques. Standard kinematic analyses were performed to extract Euler angles and equivalent screw displacement axes for paired postures. RESULTS: The three measurement techniques were highly correlated for wrist flexion-extension. Uncertainties were less than 6 degrees, similar to uncertainties from bone landmark identification errors when implanted markers cannot be used. Measures of motion exhibited higher correlations than those for alignment. Equivalent screw displacement axis orientations had poor intraclass correlations, reflecting sensitivity to coordinate system definitions. CONCLUSIONS: For motion analysis in the wrist in vivo, a non-invasive optoelectronic measurement system is as accurate as stereoradiographic analysis of bone segments.

Journal Article↗

PubMed1996

Quality of life studies in chemotherapy-induced emesis.

Health-related quality of life (HQL) was assessed before and after either moderately or highly emetogenic chemotherapy. When the pretreatment HQL in patients who did not vomit after chemotherapy (n = 203) was compared to those who vomited (n = 230), it was found that patients who did not vomit had better physical, role, and social function scores as well as a better global quality of life score than did patients who had one or more episodes of vomiting. Furthermore, in patients who did not vomit, the pretreatment fatigue and anorexia scores were better than in patients who did vomit. Thus, pretreatment HQL scores appear to have value in predicting which patients will experience chemotherapy-induced emesis. In the week following chemotherapy, HQL change scores from prechemotherapy values for cognitive function, global quality of life, fatigue, anorexia, insomnia and dyspnea were significantly worse in the group experiencing emesis than in the group who remained completely free of emesis. There were no differences in physical, role, emotional and social function attributable to chemotherapy-induced vomiting.

Antiemetics↗

PubMed1996

Increased thromboembolic complications with concurrent tamoxifen and chemotherapy in a randomized trial of adjuvant therapy for women with breast cancer. National Cancer Institute of Canada Clinical Trials Group Breast Cancer Site Group.

PURPOSE AND METHODS: Associations between thromboembolism and malignancy, usually widespread, and between thromboembolism and hormonal and/or chemotherapy have been previously reported. We performed a randomized trial of tamoxifen 30 mg/d for 2 years (T) versus T plus 6 months of intravenous chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF) for postmenopausal women with involved axillary nodes and positive estrogen receptor (ER) or progesterone receptor (PgR) status following primary therapy for breast cancer. RESULTS: We observed one or more thromboembolic events in 48 of 353 women (13.6%) allocated to receive T plus CMF in comparison to five of 352 women (2.6%) randomized to receive T alone (P < .0001). Six women in the T plus CMF arm, but none randomized to receive T alone, suffered two thromboembolic events while an study therapy. There were also significantly more women who developed severe (grade 3 to 5) thromboembolic events in the T plus CMF arm than in the T arm (34 v five; P < .0001). Most thromboembolic events (39 of 54) occurred while women were actually receiving chemotherapy (P < .0001). Thromboembolic complications resulted in more days in hospital and more deaths than any other complication of therapy, including infection, in this trial. CONCLUSION: Thromboembolism related to the addition of CMF chemotherapy to tamoxifen as adjuvant therapy in this group of women represents a relatively common and serious complication that may outweigh any benefits offered by this additional therapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

Improved local control of invasive bladder cancer by concurrent cisplatin and preoperative or definitive radiation. The National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: A prospective randomized trial was conducted to determine whether the addition of concurrent cisplatin to preoperative or definitive radiation therapy in patients with muscle-invasive bladder cancer improved local control or survival. PATIENTS AND METHODS: Ninety-nine eligible patients with T2 to T4b transitional cell bladder cancer participated, 64% with cT3b or cT4. Patients and their physicians selected either definitive radiotherapy or precystectomy radiotherapy; patients were then randomly allocated to receive intravenous cisplatin 100 mg/m2 at 2-week intervals for three cycles concurrent with pelvic radiation, or to receive radiation without chemotherapy. Patients were stratified by clinical tumor stage and by radiation plan. The median follow-up duration is 6.5 years. RESULTS: The occurrence of distant metastases was the same in both study arms. However, 25 of 48 control patients have had a first recurrence in the pelvis, compared with 15 of 51 cisplatin-treated patients (P = .036). The pelvic relapse rate in the two groups was significantly reduced by concurrent cisplatin (P = .038, log-rank test) and this effect was preserved in a stepwise Cox regression model of prognostic factors (hazards ratio, 0.50; 90% confidence interval [CI], 0.29 to 0.86; P = .036). The hazard reduction was similar for both radiation plans. Pretreatment leukocytosis and high clinical stage were independent adverse factors in a Cox model of overall survival, but the effect of cisplatin was not significant. CONCLUSION: Concurrent cisplatin may improve pelvic control of locally advanced bladder cancer with preoperative or definitive radiation, but has not been shown to improve overall survival. The use of concurrent cisplatin had no detectable effect on distant metastases.

Adult↗

PubMed1996

Influence of age on the treatment of limited-stage small-cell lung cancer.

PURPOSE: To evaluate the prognostic importance of age on response rate and survival in patients with limited-stage small-cell lung cancer (SCLC), and to determine the effect of age on chemotherapy dose delivery and toxicity. PATIENTS AND METHODS: We undertook a retrospective analysis of data from two multicenter, randomized trials conducted by the National Cancer Institute of Canada (NCIC) in which 608 SCLC patients who presented with limited disease (LD) all received the same chemotherapy. Treatment consisted of cyclophosphamide, doxorubicin, and vincristine (CAV), and etoposide plus cisplatin (EP) administered in an immediate or delayed alternating fashion, plus cranial and thoracic irradiation. RESULTS: There were 520 patients aged less than 70 years, and 88 > or = 70. No significant differences existed between the two age groups in baseline characteristics, including treatment protocol, performance status, and serum lactate dehydrogenase (LDH) level. There were more men in the older group (P = .05). Overall response rates were comparable (78% v 82%, P = .50), and 5-year survival rates were also similar (P = .14), with 11% alive in the younger group and 8% in the older group. Age was a significant predictor of overall survival when analyzed as a continuous variable in a univariate model (P = .01), but it was no longer an independent prognostic factor in our multivariate regression analysis. An analysis of chemotherapy delivery between the two age groups showed that patients aged > or = 70 years received lower total doses of each drug compared with the intended full protocol dose, primarily as a result of dose omissions, rather than dose reductions. The frequency of dose delays was not different between groups. No significant differences were seen in the incidence of either hematologic or most nonhematologic toxicities. CONCLUSION: Age is not a significant adverse prognostic variable in SCLC patients with LD. Moderately aggressive chemotherapy may be delivered safely to elderly patients with a good performance status, although modest attenuation of therapy through either dose reduction or omission may occur more frequently in this population.

Adolescent↗