Health-related quality of life in men with metastatic prostate cancer treated with prednisone alone or mitoxantrone and prednisone.
(65/2596)
PURPOSE: A combination of mitoxantrone plus prednisone is preferable to prednisone alone for reduction of pain in men with metastatic, hormone-resistant, prostate cancer. The purpose of this study was to assess the effects of these treatments on health-related quality of life (HQL). PATIENTS AND METHODS: Men with metastatic prostate cancer (n = 161) were randomized to receive either daily prednisone alone or mitoxantrone (every 3 weeks) plus prednisone. Those who received prednisone alone could have mitoxantrone added after 6 weeks if there was no improvement in pain. HQL was assessed before treatment initiation and then every 3 weeks using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire C30 (EORTC QLQ-C30) and the Quality of Life Module-Prostate 14 (QOLM-P14), a trial-specific module developed for this study. An intent-to-treat analysis was used to determine the mean duration of HQL improvement and differences in improvement duration between groups of patients. RESULTS: At 6 weeks, both groups showed improvement in several HQL domains, and only physical functioning and pain were better in the mitoxantrone-plus-prednisone group than in the prednisone-alone group. After 6 weeks, patients taking prednisone showed no improvement in HQL scores, whereas those taking mitoxantrone plus prednisone showed significant improvements in global quality of life (P =.009), four functioning domains, and nine symptoms (.001 < P <. 01), and the improvement (> 10 units on a scale of 0 to100) lasted longer than in the prednisone-alone group (.004 < P <.05). The addition of mitoxantrone to prednisone after failure of prednisone alone was associated with improvements in pain, pain impact, pain relief, insomnia, and global quality of life (.001 < P <.003). CONCLUSION: Treatment with mitoxantrone plus prednisone was associated with greater and longer-lasting improvement in several HQL domains and symptoms than treatment with prednisone alone. (+info)
Locoregional failure 10 years after mastectomy and adjuvant chemotherapy with or without tamoxifen without irradiation: experience of the Eastern Cooperative Oncology Group.
(66/2596)
PURPOSE: To assess patterns of failure and how selected prognostic and treatment factors affect the risks of locoregional failure (LRF) after mastectomy in breast cancer patients with histologically involved axillary nodes treated with chemotherapy with or without tamoxifen without irradiation. PATIENTS AND METHODS: The study population consisted of 2,016 patients entered onto four randomized trials conducted by the Eastern Cooperative Oncology Group. The median follow-up time for patients without recurrence was 12.1 years (range, 0.07 to 19.1 years). RESULTS: A total of 1,099 patients (55%) experienced disease recurrence. The first sites of failure were as follows: isolated LRF, 254 (13%); LRF with simultaneous distant failure (DF), 166 (8%); and distant only, 679 (34%). The risk of LRF with or without simultaneous DF at 10 years was 12.9% in patients with one to three positive nodes and 28.7% for patients with four or more positive nodes. Multivariate analysis showed that increasing tumor size, increasing numbers of involved nodes, negative estrogen receptor protein status, and decreasing number of nodes examined were significant for increasing the rate of LRF with or without simultaneous DF. CONCLUSION: LRF after mastectomy is a substantial clinical problem, despite the use of chemotherapy with or without tamoxifen. Prospective randomized trials will be necessary to estimate accurately the potential disease-free and overall survival benefits of postmastectomy radiotherapy for patients in particular prognostic subgroups treated with presently used and future systemic therapy regimens. (+info)
Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group.
(67/2596)
PURPOSE: Progestins have definite activity against advanced or recurrent endometrial carcinoma. Both parenteral and oral progestins yield similar serum levels and response rates, which range from 18% to 34%. The one major study that used oral medroxyprogesterone acetate (MPA) noted a response rate at the lower end of the range (18%) and much poorer progression-free and overall survival times (4 and 10.5 months, respectively) than previously reported. The present study sought to confirm this earlier study of oral MPA, to assess the importance of prognostic factors such as histologic grade and receptor levels, and to determine whether a higher dose of MPA would yield a higher response rate. PATIENTS AND METHODS: Two hundred ninety-nine eligible women with advanced or recurrent endometrial carcinoma were randomized to receive oral MPA either 200 mg/d or 1, 000 mg/d until unacceptable toxicity intervened or their disease progressed. RESULTS: Among 145 patients receiving the low-dose regimen, there were 25 complete (17%) and 11 partial (8%) responses for an overall response rate of 25%. The 154 patients receiving the high-dose regimen experienced 14 (9%) complete and 10 (6%) partial responses for an overall response rate of 15%. Median durations of progression-free survival were 3.2 months and 2.5 months for the low-dose and high-dose regimens, respectively. Median survival durations were 11.1 months and 7.0 months, respectively. The adjusted relative odds of responding to the high-dose regimen compared with the low-dose regimen was 0.61 (90% confidence interval, 0.36 to 1.04). Prognostic factors having a significant impact on the probability of response included initial performance status, age, histologic grade, and progesterone receptor concentration. Compliance with oral therapy was documented with serum levels 1 month after starting therapy, when possible. MPA levels were commensurate with the assigned dose and schedule. CONCLUSION: Oral MPA is active against endometrial carcinoma. Response to progestin therapy is more frequent among patients with a well-differentiated histology and positive progesterone receptor status. This study provides no evidence to support the use of MPA 1,000 mg/d orally instead of MPA 200 mg/d orally. In fact, the trends suggest the opposite. The use of oral MPA 200 mg/d is a reasonable initial approach to the treatment of advanced or recurrent endometrial carcinoma, particularly those lesions that are well-differentiated and/or progesterone receptor-positive (> 50 fmol/mg cytosol protein). Patients with poorly differentiated and/or progesterone receptor levels less than 50 fmol/mg cytosol protein had only an 8% to 9% response rate. (+info)
Epirubicin plus tamoxifen versus tamoxifen alone in node-positive postmenopausal patients with breast cancer: A randomized trial of the International Collaborative Cancer Group.
(68/2596)
PURPOSE: To assess whether the addition of epirubicin (EPI) therapy to prolonged treatment with tamoxifen (TAM) improves relapse-free and overall survival in postmenopausal women with node-positive primary breast cancer. PATIENTS AND METHODS: Six hundred four patients entered onto a randomized clinical trial were allocated to receive TAM 20 mg/d for 4 years or TAM 20 mg/d for 4 years plus EPI 50 mg/m(2) intravenously on days 1 and 8 every 4 weeks for six cycles. Analysis was performed according to allocated treatment, with all randomized patients included (intention to treat), irrespective of eligibility status. RESULTS: After a median follow-up period of 5.7 years, an improvement in relapse-free survival (RFS) was observed for the TAM and EPI-treated patients, compared with those who received TAM alone. The unadjusted hazard ratio was 0.72 (95% confidence interval, 0.54 to 0.96), with a corresponding reduction in the odds of recurrence of 27.9% (SD, 12. 3), which was statistically significant (P =.023). Adjustment for prognostic and/or predictive factors did not materially affect the hazard ratio. No difference was observed in terms of overall survival (reduction in odds of death, 11.9% [SD, 16.3]; P =.46). Combined chemohormonal treatment was associated with a higher incidence of acute side effects but without a clear increase in long-term cardiotoxicity. Twelve nonbreast second malignancies, including five hematologic malignancies (two of which were cases of acute myelogenous leukemia), were observed. CONCLUSION: The data show that combined chemohormonal treatment reduces the risk of relapse in postmenopausal patients with node-positive breast cancer. No evidence was found, however, for an improvement in overall survival. The size of benefit observed for both outcomes was consistent with that reported in the Early Breast Cancer Trialists' Collaborative Group overview. The trial presented here, however, provides the first report of an improvement in RFS associated with the provision of a single cytotoxic drug in addition to prolonged TAM. (+info)
Outcomes of high-dose chemotherapy and autologous stem-cell transplantation in stage IIIB inflammatory breast cancer.
(69/2596)
PURPOSE: To evaluate the disease-free survival (DFS) and overall survival (OS), prognostic factors, and treatment-related mortality of women with stage IIIB inflammatory breast cancer (IBC) treated with combined modality therapy (CMT) and high-dose chemotherapy (HDCT) with autologous stem-cell transplantation. PATIENTS AND METHODS: Between 1989 and 1997, 47 consecutive patients with stage IIIB IBC were treated with CMT and HDCT and were the subject of this retrospective analysis. Chemotherapy was administered to all patients before and/or after definitive surgery. Neoadjuvant and adjuvant chemotherapy was administered to 33 and 34 patients, respectively, and 20 patients received both. All patients received HDCT with autologous stem-cell transplantation, and 41 patients received locoregional radiation therapy. Tamoxifen was prescribed to patients with estrogen receptor (ER)-positive cancer. RESULTS: The mean duration of follow-up from diagnosis was 30 months (range, 6 to 91 months) and from HDCT was 22 months (range, 0.5 to 82 months). At 30 months, the Kaplan-Meier estimates of DFS and OS from diagnosis were 57.7% and 59.1%, respectively. At 4 years, the Kaplan-Meier estimates of DFS and OS from diagnosis were 51.3% and 51.7%, respectively. In a multivariate analysis, the only factors associated with better survival were favorable response to neoadjuvant chemotherapy (P =.04) and receipt of tamoxifen (P =.06); however, the benefit of tamoxifen was only demonstrated in patients with ER-positive breast cancer. At last follow-up, 28 patients (59. 6%) were alive and disease-free. Seventeen patients (36.2%) developed recurrent breast cancer. Seventeen patients died: 15 from disease recurrence and two (4.2%) from treatment-related mortality due to HDCT. CONCLUSION: In this analysis, the early results of treatment with CMT and HDCT compare favorably with other series of patients with stage IIIB IBC treated with CMT alone. These outcomes must be confirmed with longer follow-up and controlled studies. (+info)
Bicalutamide monotherapy versus flutamide plus goserelin in prostate cancer patients: results of an Italian Prostate Cancer Project study.
(70/2596)
PURPOSE: To compare the efficacy of bicalutamide monotherapy to maximal androgen blockade (MAB) in the treatment of advanced prostatic cancer. PATIENTS AND METHODS: Previously untreated patients with histologically proven stage C or D disease (American Urological Association Staging System) were randomly allocated to receive either bicalutamide or MAB. After disease progression, patients treated with bicalutamide were assigned to castration. The primary end point for this trial was overall survival. Secondary end points included response to treatment, disease progression, treatment safety, quality-of-life (QOL), and sexual function. RESULTS: A total of 108 patients received bicalutamide and 112 received MAB. There was no difference in the percentage of patients whose prostate-specific antigen returned to normal levels. At the time of the present analysis (median follow-up time, 38 months; range, 1 to 60 months), 129 patients progressed and 89 died. There was no difference in the duration of either progression-free survival or overall survival. However, a survival trend favored bicalutamide in stage C disease but MAB in stage D disease. Overall and subgroup trends were confirmed by multivariate analysis. Serious adverse events and treatment discontinuations were more common in patients receiving MAB (P =.08 and P =.04, respectively). Fewer patients in the bicalutamide group complained of loss of libido (P =. 01) and of erectile dysfunction (P =.002). Significant trends favored bicalutamide-treated patients also with respect to their QOL, namely relative to social functioning, vitality, emotional well-being, and physical capacity. CONCLUSION: Bicalutamide monotherapy yielded comparable results relative to standard treatment with MAB, induced fewer side effects, and produced a better QOL. (+info)
Investigation of endometrial abnormalities in asymptomatic women treated with tamoxifen and an evaluation of the role of endometrial screening.
(71/2596)
PURPOSE: Tamoxifen is the most commonly prescribed adjuvant therapy for women with breast cancer. It has agonist activity on the endometrium and is associated with an increased risk of endometrial cancer. The aim of this study was to evaluate whether screening with transvaginal ultrasound (TV USS) with or without hysteroscopy is worthwhile. PATIENTS AND METHODS: A total of 487 women with breast cancer, 357 treated with tamoxifen and 130 controls, were screened with TV USS, and endometrial thickness was measured. Women with thickened endometrium underwent outpatient hysteroscopy. RESULTS: Length of time on tamoxifen ranged from 5 to 191 months (mean, 66 months), and endometrial thickness ranged from 1 to 38 mm (mean, 7.3 mm). Women treated with tamoxifen had significantly thicker endometrium than did controls (P <.0001). There was a statistically significant (P <.0001) positive correlation between length of time on tamoxifen and endometrial thickness. One hundred forty-five women had endometrium greater than 5 mm on USS, and 134 underwent successful outpatient hysteroscopy, 61 of whom had atrophic endometrium, resulting in a 46% false-positive scan rate. The remaining women all had benign features to explain the USS findings. CONCLUSION: TV USS detects a high incidence (41%) of apparent endometrial thickening in women treated with tamoxifen, although 46% had atrophic endometrium on further assessment, and none of the remaining asymptomatic women had significant lesions. Length of time on tamoxifen relates to endometrial thickening as measured by TV USS. TV USS is a poor screening tool because of the high false-positive rate. The low frequency of significant findings suggests that endometrial screening in asymptomatic women is not worthwhile. (+info)
Effect of blood tamoxifen concentrations on surrogate biomarkers in a trial of dose reduction in healthy women.
(72/2596)
PURPOSE: Tamoxifen administered at 20 mg/d has been shown to decrease breast cancer incidence in at-risk women by 50%, but toxicity may limit its broad use, particularly in postmenopausal women. Because toxicity may be dose-dependent, we studied the biologic activity of low concentrations of tamoxifen to determine the plausibility of a dose reduction. PATIENTS AND METHODS: We measured the blood concentrations of tamoxifen and its main metabolites in a dose titration study in 105 healthy women (placebo, tamoxifen 10 mg on alternate days, tamoxifen 10 mg/d, and tamoxifen 20 mg/d). Drug levels measured after 2 months of treatment were correlated with the changes in surrogate biomarkers of different diseases, including lipid profile, blood cell count, fibrinogen, antithrombin III, osteocalcin, and insulin-like growth factor I, a promising surrogate biomarker of breast cancer. RESULTS: The means (+/- SD) for tamoxifen and N-desmethyltamoxifen (metabolite X) concentrations (ng/mL) were dose-related, being, respectively, 0 and 0 with placebo, 26.8 +/- 15.1 and 43.7 +/- 22.5 with 10 mg every other day, 51.2 +/- 24.1 and 90.7 +/- 48.0 with 10 mg/d, and 136.0 +/- 52.7 and 230.6 +/- 75.0 with 20 mg/d of tamoxifen. At variance, the biomarker changes were of comparable magnitude at any drug concentration except for platelet count and triglycerides levels, the latter showing a trend to an increase with increasing tamoxifen concentrations. CONCLUSION: An 80% reduction in blood concentrations does not seem to affect the activity of tamoxifen on biomarkers of cardiovascular or breast cancer risk and may in fact have a more favorable safety profile. Additional studies are warranted to determine the most appropriate dose of this agent. (+info)