Michael Palmer

Goserelin versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy in premenopausal patients with node-positive breast cancer: The Zoladex Early Breast Cancer Research Association Study

PURPOSE Current adjuvant therapies have improved survival for premenopausal patients with breast cancer but may have short-term toxic effects and long-term effects associated with premature menopause. PATIENTS AND METHODS The Zoladex Early Breast Cancer Research Association study assessed the efficacy and tolerability of goserelin (3.6 mg every 28 days for 2 years; n = 817) versus cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy (six 28-day cycles; n = 823) for adjuvant treatment in premenopausal patients with node-positive breast cancer. RESULTS Analysis was performed when 684 events had been achieved, and the median follow-up was 6 years. A significant interaction between treatment and estrogen receptor (ER) status was found (P =.0016). In ER-positive patients (approximately 74%), goserelin was equivalent to CMF for disease-free survival (DFS) (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.84 to 1.20). In ER-negative patients, goserelin was inferior to CMF for DFS (HR, 1.76; 95% CI, 1.27 to 2.44). Amenorrhea occurred in more than 95% of goserelin patients by 6 months versus 58.6% of CMF patients. Menses returned in most goserelin patients after therapy stopped, whereas amenorrhea was generally permanent in CMF patients (22.6% v 76.9% amenorrheic at 3 years). Chemotherapy-related side effects such as nausea/vomiting, alopecia, and infection were higher with CMF than with goserelin during CMF treatment. Side effects related to estrogen suppression were initially higher with goserelin, but when goserelin treatment stopped, reduced to a level below that observed in the CMF group. CONCLUSION Goserelin offers an effective, well-tolerated alternative to CMF in premenopausal patients with ER-positive and node-positive early breast cancer.

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.

Comparison of the efficacy and safety of rosuvastatin 10 mg and atorvastatin 20 mg in high-risk patients with hypercholesterolemia--Prospective study to evaluate the Use of Low doses of the Statins Atorvastatin and Rosuvastatin (PULSAR).

BackgroundMany patients at high risk of cardiovascular disease do not achieve recommended low-density lipoprotein cholesterol (LDL-C) goals. This study compared the efficacy and safety of low doses of rosuvastatin (10 mg) and atorvastatin (20 mg) in high-risk patients with hypercholesterolemia.MethodsA total of 996 patients with hypercholesterolemia (LDL-C ≥ 3.4 and < 5.7 mmol/L [130 and 220 mg/dL]) and coronary heart disease (CHD), atherosclerosis, or a CHD-risk equivalent were randomized to once-daily rosuvastatin 10 mg or atorvastatin 20 mg. The primary endpoint was the percentage change from baseline in LDL-C levels at 6 weeks. Secondary endpoints included LDL-C goal achievement (National Cholesterol Education Program Adult Treatment Panel III [NCEP ATP III] goal < 100 mg/dL; 2003 European goal < 2.5 mmol/L for patients with atherosclerotic disease, type 2 diabetes, or at high risk of cardiovascular events, as assessed by a Systematic COronary Risk Evaluation (SCORE) risk ≥ 5% or 3.0 mmol/L for all other patients), changes in other lipids and lipoproteins, cost-effectiveness, and safety.ResultsRosuvastatin 10 mg reduced LDL-C levels significantly more than atorvastatin 20 mg at week 6 (44.6% vs. 42.7%, p < 0.05). Significantly more patients achieved NCEP ATP III and 2003 European LDL-C goals with rosuvastatin 10 mg compared with atorvastatin 20 mg (68.8% vs. 62.5%, p < 0.05; 68.0% vs. 63.3%, p < 0.05, respectively). High-density lipoprotein cholesterol was increased significantly with rosuvastatin 10 mg versus atorvastatin 20 mg (6.4% vs. 3.1%, p < 0.001). Lipid ratios and levels of apolipoprotein A-I also improved more with rosuvastatin 10 mg than with atorvastatin 20 mg. The use of rosuvastatin 10 mg was also cost-effective compared with atorvastatin 20 mg in both a US and a UK setting. Both treatments were well tolerated, with a similar incidence of adverse events (rosuvastatin 10 mg, 27.5%; atorvastatin 20 mg, 26.1%). No cases of rhabdomyolysis, liver, or renal insufficiency were recorded.ConclusionIn high-risk patients with hypercholesterolemia, rosuvastatin 10 mg was more efficacious than atorvastatin 20 mg at reducing LDL-C, enabling LDL-C goal achievement and improving other lipid parameters. Both treatments were well tolerated.

Costs incurred by patients undergoing advanced colorectal cancer therapy. A comparison of raltitrexed and fluorouracil plus folinic acid.

Background: To assess the cost effectiveness of healthcare interventions from a societal perspective, it is necessary to include costs such as patients’ travel costs and the opportunity cost of patients’ time spent consuming healthcare.Objective: To analyse patients’ travel and time costs associated with 2 alternative drug therapies for advanced colorectal cancer: raltitrexed and fluorouracil plus folinic acid (leucovorin) [5FU + FA].Design and setting: The analysis is based on a prospective substudy within a multinational randomised controlled trial of raltitrexed versus 5FU + FA.Patients and participants: 495 patients with advanced colorectal cancer were enrolled in the trial, 270 of whom completed the questionnaire on costs.Methods: Data were collected within the trial to estimate the numbers of journeys made to and from hospital by patients and the time lost from usual activities over the period of therapy. A subset of patients were asked to complete a questionnaire to provide the information necessary to value time and travel costs in monetary terms. These data, together with UK transport costs and forgone time values, were used to value the transport and opportunity costs of time of all patients in the trial.Results: The total travel cost per patient was statistically significantly higher in the 5FU + FA group (p > 0.001; median of £31.50 with raltitrexed, £96.00 with 5FU + FA; 1997 prices). Overall time cost per patient was also higher in the 5FU + FA group (p = 0.005; median of £168.80 with raltitrexed, £224.04 with 5FU + FA). Adding the two gives a median total cost per patient of £206.08 [interquartile range (IQR) £108 to £482] among patients randomised to raltitrexed and £342.25 (IQR £214 to £555) for those in the 5FU + FA group (p > 0.001). The sensitivity analysis showed that, even under extreme assumptions, raltitrexed imposed fewer time and travel costs on patients. These cost differences are likely, in part, to reflect the longer treatment times for 5FU + FA patients (median 16.9 vs 12.7 weeks).Conclusions: Different chemotherapy regimens for advanced colorectal cancer can impose different travel and time costs on patients. Over the period of treatment in a randomised controlled trial of 495 patients, those randomised to 5FU + FA were found to have a median travel plus time cost £136 per patient higher than those randomised to raltitrexed.

Lessons Learned in the Assessment of Health-Related Quality of Life: Selected Examples From the National Cancer Institute of Canada Clinical Trials Group

In this article, we provide a brief historical review of the development of patient-reported outcome measurement, analysis, and reporting in clinical trials of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG). In doing so, we examine selected lessons learned in furthering the quality of these data and their application to clinical practice. We conclude that sequential institution of key policies within the NCIC CTG and the development of a collective philosophy within the group has enabled the routine incorporation of health-related quality of life into clinical trial protocols according to robust scientific principles; that collection of quality data is possible in a variety of circumstances (although not universally so); that patient-reported data on subjective experiences is likely to be more reliable and valid than conventional toxicity information; and that simple analyses that report group trends as well as individual patient response rates are preferred.