PubMed Health⌕ Search

Biomedical subjects

J W Meakin

Publications and source records attributed to J W Meakin.

At least 19 recordsLinked to original sources
PubMed1998

Analysis of cause-specific failure endpoints using simple proportions: an example from a randomized controlled clinical trial in early breast cancer.

PURPOSE: To describe a statistically valid method for analyzing cause-specific failure data based on simple proportions, that is easy to understand and apply, and outline under what conditions its implementation is well-suited. METHODS AND MATERIALS: In the comparison of treatment groups, time to first failure (in any site) was analyzed first, followed by an analysis of the pattern of first failure, preferably at the latest complete follow-up time common to each group. RESULTS: A retrospective analysis of time to contralateral breast cancer in 777 early breast cancer patients was undertaken. Patients previously treated by mastectomy plus radiation therapy to the chest wall and regional nodal areas were randomized to receive further radiation and prednisone (R+P), radiation alone (R), or no further treatment (NT). Those randomized to R+P had a statistically significantly delayed time to first failure compared to the group randomized to NT (p = 0.0008). Patients randomized to R also experienced a delayed time to first failure compared to NT, but the difference was not statistically significant (p = 0.14). At 14 years from the date of surgery (the latest common complete follow-up time) the distribution of first failures was statistically significantly different between R+P and NT (p = 0.005), but not between R and NT (p = 0.09). The contralateral breast cancer first failure rate at 14 years from surgery was 7.2% for NT, 4.6% for R, and 3.7% for R+P. The corresponding Kaplan-Meier estimates were 13.2%, 8.2%, and 5.4%, respectively. CONCLUSION: Analyzing cause-specific failure data using methods developed for survival endpoints is problematic. We encourage the use of the two-step analysis strategy described when, as in the example presented, competing causes of failure are not likely to be statistically independent, and when a treatment comparison at a single time-point is clinically relevant and feasible; that is, all patients have complete follow-up to this point.

Adult↗
PubMed1997

An individual patient-based meta-analysis of tamoxifen versus ovarian ablation as first line endocrine therapy for premenopausal women with metastatic breast cancer.

We performed a meta-analysis of randomized trials comparing tamoxifen to ovarian ablation carried out either by surgery or irradiation as first-line hormonal therapy for pre-menopausal women with metastatic breast cancer. Patients in all trials included were required to have measurable disease and to be currently menstruating or within 1 year of cessation of menses, and to have estrogen receptor (ER) positive or unknown disease (ER negative women were admitted to one of the studies). Individual patient data were obtained from the four studies identified and the results updated to June 1992. A total of 220 eligible patients were enrolled in the four trials. There was no difference in overall response rate between tamoxifen and oophorectomy across the four trials (p = 0.94, Mantel-Haenszel test). The odds reduction for progression was 14% +/- 12% and for mortality 6% +/- 13% in favour of tamoxifen, results which were not statistically significant (p = 0.32 and 0.72, respectively). Although the design of all four studies included a cross-over to the other therapy, only 54/111 patients receiving ovarian ablation and 34/109 patients receiving tamoxifen as primary therapy actually crossed over to the other arm at the time of disease progression. Response to initial treatment with tamoxifen was predictive of subsequent response to ovarian ablation (p < 0.05), and response to initial therapy with ovarian ablation was predictive of subsequent response to tamoxifen (p < 0.05). Support curves based on log-likelihood ratios revealed that this meta-analysis provides moderate evidence rejecting a 14% advantage for ovarian ablation compared to tamoxifen in terms of odds of disease progression. A 25% advantage for ovarian ablation with respect to odds of death is also rejected with moderate evidence. We conclude that the efficacy of tamoxifen appears to be similar to that of ovarian ablation by surgery or irradiation as first-line therapy for premenopausal, ER positive metastatic breast cancer, and is unlikely to be substantially inferior.

Adult↗
PubMed1997

A randomized crossover trial of tamoxifen versus ovarian ablation for metastatic breast cancer in premenopausal women: a report of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trial MA.1.

We concluded a randomized crossover trial comparing tamoxifen 40 mg daily with ovarian ablation for treatment of metastatic breast cancer in premenopausal women. Objective responses (complete response (CR) plus partial response (PR)) were observed in 5/20 patients treated initially with tamoxifen and in 3/19 patients initially treated with ovarian ablation (p = 0.69). Seven additional patients were stable (SD) on tamoxifen while five additional patients were stable after ovarian ablation, for CR + PR + SD rates of 12/20 (60%) for tamoxifen and 8/19 (42%) for ovarian ablation (p = 0.34). Median time to disease progression was 184 days for tamoxifen and 126 days for ovarian ablation (p = 0.40, logrank test, odds ratio for progression 0.71). Overall survival times were also similar: a median of 2.35 years for tamoxifen and 2.46 years for ovarian ablation (p = 0.98, logrank test, odds ratio for death 1.07). Side effects from tamoxifen included hot flashes and menstrual abnormalities. With one exception, these toxicities were not sufficient to require dose reduction. In this small study, tamoxifen was associated with similar response rates, response durations, and survival times to those observed with ovarian ablation.

Adult↗
PubMed1996

Ovarian irradiation and prednisone following surgery and radiotherapy for carcinoma of the breast.

Following mastectomy, patients aged 35 to 76 years with operable breast cancer underwent postoperative irradiation of the chest wall and regional lymph nodes. They were then assigned at random to receive no further therapy (NT), ovarian irradiation (R) 2000 rads in 5 days, or ovarian irradiation in the same dosage plus prednisone (R + P) 7.5 mg daily for up to five years. A total of 703 eligible patients received the randomly assigned treatment. The median follow up was 21 years with a range of 14 to 25 years. Overall, there was a delay in recurrence (p = 0.03) and survival was prolonged (p = 0.19) for patients who received R, but in neither case was the difference significant after adjusting for the multiplicity in our data. Overall, patients who received R + P experienced a significant delay in recurrence (p = 0.0003) and a significantly prolonged survival (p = 0.005), even after adjusting for multiple comparisons. In premenopausal patients who received R, the recurrence of breast cancer was delayed and survival prolonged, but not significantly. In premenopausal women aged 45 years or more, R + P therapy significantly prolonged survival (p = 0.0004), while the delay in recurrence although significant (p = 0.02) was only marginally so after allowance for multiple comparisons. No value was demonstrated for ovarian irradiation with or without prednisone therapy in postmenopausal patients. A new finding in this review was that contralateral breast cancer as the first failure was reduced by R + P compared to NT in the overall group.

Adult↗
PubMed1986

Role and mechanism of action of tamoxifen in premenopausal women with metastatic breast carcinoma.

Tamoxifen was evaluated as initial hormone therapy for metastatic breast cancer in 85 premenopausal patients. Tamoxifen responders continued on tamoxifen, while tamoxifen failures and initial responders who later progressed were to receive ovarian ablation next. Of 74 evaluable patients, 5 had complete responses (CR) and 15 had partial responses (PR) while 12 remained stable (ST), giving response rates of 27% (CR + PR) or 43% (CR + PR + ST). Of the 23 patients who initially responded (CR + PR + ST) to tamoxifen but then progressed and received ovarian ablation alone, 15 are assessable. Nine (60%) responded (CR + PR + ST) to ovarian ablation. Sixteen patients who failed tamoxifen had ovarian ablation alone, and of 14 assessable patients 2 had ST while 12 progressed. Thus response to tamoxifen strongly predicted response to ovarian ablation (P = 0.021). Serial follicle stimulating hormone, prolactin, and estradiol levels suggested that tamoxifen does not act by induction of a "medical ovariectomy" or by alteration of prolactin levels in premenopausal patients.

Breast Neoplasms↗
PubMed1986

Review of Canadian trials of adjuvant endocrine therapy for breast cancer.

Adjuvant ovarian ablation delays recurrence and prolongs survival in premenopausal patients with breast cancer, but the differences fall short of statistical significance; this effect is enhanced to statistically significant differences by low-dose prednisone. Adjuvant tamoxifen has delayed recurrence in post-menopausal patients with steroid receptor-positive tumors and positive axillary nodes, but, to date, has not affected survival.

Adult↗
PubMed1983

Ovarian irradiation and prednisone following surgery and radiotherapy for carcinoma of the breast.

Following mastectomy, patients with operable breast cancer underwent postoperative irradiation of the chest wall and regional lymph nodes. They were then assigned at random to receive no further therapy, ovarian irradiation (2000 rad in five days) or ovarian irradiation in the same dosage plus prednisone, 7.5 mg daily. A total of 705 patients received the randomly assigned treatment and were followed for up to 15 years. In premenopausal patients who received ovarian irradiation, the recurrence of breast cancer was delayed and survival prolonged, but not significantly. In premenopausal women aged 45 years or more, ovarian irradiation plus prednisone therapy significantly delayed the recurrence of breast cancer (p = 0.04) and prolonged survival (p = 0.02). No value was demonstrated for ovarian irradiation with or without prednisone therapy in postmenopausal patients.

Adult↗
PubMed1981

Clinical estimation of the growth rate of breast cancer.

To test the ability of the patient's history to provide prognostically important information in breast cancer the authors used information prospectively collected by interview from 756 patients enrolled in a randomized controlled trial of adjuvant therapy. Classification of this information according to the principles of rate of growth created groups with substantial and statistically significant differences in survival. The survival differences created by classifying growth rate were comparable to those created by other prognostic factors, and independent of those created by stage, lymph node status or tumor grade. The patient's history in breast cancer is capable of providing reproducible prognostic information when it is suitable classified, and this information represents a useful addition to current methods of estimating prognosis in breast cancer.

Adult↗
PubMed1981

Body weight and prognosis in breast cancer.

We have examined the relationship between risk factors for breast cancer incidence and the subsequent prognosis of breast cancer among patients in a randomized controlled trial of adjuvant ovarian ablation. Body weight was the only risk factor found to be associated with statistically significant differences in survival. This finding could not be explained by a disproportionate number of anatomically more advanced tumors in the heavier women. In premenopausal women aged 45 years or more, the only group to benefit from adjuvant ovarian ablation, there was an interaction of treatment and weight, suggesting that weight exerts its influence on prognosis by a hormonal mechanism. The prognostic effect of weight was generally most marked in patients with tumors whose prognostic characteristics were favorable, and in these patients weight loss as an adjuvant treatment may reduce the frequency of disease recurrence.

Adult↗
PubMed1979

Ovarian irradiation and prednisone therapy following surgery and radiotherapy for carcinoma of the breast.

Following mastectomy, patients with operable breast cancer underwent postoperative irradiation of the chest wall and regional lymph nodes. They were then assigned at random to receive no further therapy, ovarian irradiation (2000 rads in 5 days) or ovarian irradiation in the same dosage plus prednisone, 7.5 mg daily. A total of 705 patients received the randomly assigned treatment and were followed for up to 10 years. In premenopausal patients who received ovarian irradiation the recurrence of breast cancer was delayed and survival prolonged, but not significantly. In premenopausal women aged 45 years or more ovarian irradiation plus prednisone therapy significantly delayed the recurrence of breast cancer (P = 0.02) and prolonged survival (P = 0.02); the survival expectancy of these patients was similar to that of the general population of the same age from the third year after the cancer operation. No value was demonstrated for ovarian irradiation with or without prednisone therapy in postmenopausal patients.

Adult↗
PubMed1978

Carcinoembryonic antigen in breast cancer.

Carcinoembryonic antigen (CEA) levels were determined in 742 postoperative patients with breast cancer. Within this group the percentage of elevated (greater than or equal to 4.0 ng/ml) assays increased with UICC clinical stage and was 14.8% (12/81), 23.7% (27/114), 73.1% (190/260) and 20.0% (49/245) for stages I, II, III, IV and X (unstagable due to insufficient data) patients. We have now followed the above 482 stages I, II, III and X patients in whom CEA was performed less than or equal to 3 months after initial surgery at a time when there was no evidence of residual disease, for an average interval of 255 days from date of diagnosis. At present 16.2% (17/105) of patients with elevated CEA values compared to only 4.8% (18/377) of patients with normal values have developed recurrent disease (p less than .0005). There is an association of elevation of CEA postoperatively with different clinical stages of breast cancer. Elevated CEA levels postoperatively are associated with an increased risk of development of recurrent disease in breast cancer patients.

Breast Neoplasms↗