First-line Herceptin monotherapy in metastatic breast cancer.

The pivotal phase II and III Herceptin trials proved the efficacy and safety of second- or third-line single-agent Herceptin and first-line Herceptin in combination with chemotherapy, respectively. In the current trial, 114 patients were randomized to one of two dose groups of first-line Herceptin monotherapy: standard dose of 4 mg/ kg initial dose followed by 2 mg/kg intravenous (i.v.) weekly; or high dose of 8 mg/kg initial dose followed by 4 mg/kg i.v. weekly. The regimen was generally well tolerated. A similar incidence of adverse events was demonstrated in the two dose groups with the possible exception of acute infusion-related events such as fever and chills as well as rash and dyspnea, which appear to be more prevalent in the higher dose group. The overall response rate was 26% and response rates were similar between the two dose groups (24% for the standard Herceptin dose group and 28% for the high Herceptin dose group). Subgroup analysis determined a higher response rate in IHC 3+ patients (35%) and FISH-positive patients (41%). When women with stable disease for > or =6 months were included with responders, the clinical benefit rate in IHC 3+ patients was 47%. Median survival was 24.4 months, which is comparable with the survival rate seen in the pivotal phase III combination trial (25 months). Therefore, single-agent Herceptin is an important new option for the first-line treatment of HER2-positive metastatic breast cancer patients.

First-line, single-agent Herceptin(R) (trastuzumab) in metastatic breast cancer. a preliminary report.

Following confirmation of the appropriate dosage, safety and potential efficacy of Herceptin(R) (trastuzumab) in small-scale phase I and II trials involving patients with refractory disease, a large trial was conducted in 222 patients with breast cancer who had relapsed after one or two chemotherapy regimens for their metastatic disease. The results showed a positive and durable overall response rate (15% according to a response evaluation committee (REC) assessment) using trastuzumab monotherapy (initial dose 4 mg/kg intravenously (i.v.) followed by 2 mg/kg i.v. weekly). In another recently completed phase II trial, 113 patients were randomised to two dose levels (initial dose of 4 mg/kg i.v. dose followed by 2 mg/kg i.v. weekly, or initial dose of 8 mg/kg followed by 4 mg/kg i.v. weekly) of single-agent trastuzumab as first-line therapy for metastatic disease. The preliminary overall response rate was 23% based on investigator assessment, and tolerability was excellent as in previous trials; efficacy was similar in both dose groups, but the side-effects tended to be more frequent in the higher dose group. The preferred dosage is therefore the same as that currently recommended, i.e. an initial dose of 4 mg/kg i.v. followed by 2 mg/kg weekly i.v. until disease progression.

First-line, single-agent Herceptin(trastuzumab) in metastatic breast cancer: a preliminary report.

Following confirmation of the appropriate dosage, safety and potential efficacy of Herceptin(trastuzumab) in small-scale phase I and II trials involving patients with refractory disease, a large trial was conducted in 222 patients with breast cancer who had relapsed after one or two chemotherapy regimens for their metastatic disease. The results showed a positive and durable overall response rate (15% according to a response evaluation committee (REC) assessment) using trastuzumab monotherapy (initial dose 4 mg/kg intravenously (i.v.) followed by 2 mg/kg i.v. weekly). In another recently completed phase II trial, 113 patients were randomised to two dose levels (initial dose of 4 mg/kg i.v. dose followed by 2 mg/kg i.v. weekly, or initial dose of 8 mg/kg followed by 4 mg/kg i.v. weekly) of single-agent trastuzumab as first-line therapy for metastatic disease. The preliminary overall response rate was 23% based on investigator assessment, and tolerability was excellent as in previous trials; efficacy was similar in both dose groups, but the side-effects tended to be more frequent in the higher dose group. The preferred dosage is therefore the same as that currently recommended, i.e. an initial dose of 4 mg/kg i.v. followed by 2 mg/kg weekly i.v. until disease progression.

Health-related quality of life in women with metastatic breast cancer treated with trastuzumab (Herceptin).

The measurement of health-related quality of life (HRQL) was an important component of clinical trials of trastuzumab (Herceptin; Genentech, San Francisco, CA) in women with progressive HER2-overexpressing metastatic breast cancer who may or may not have had prior chemotherapy. Health-related quality of life was measured at baseline and specified intervals during therapy using the European Organization for Research and Treatment of Cancer core Quality of Life Questionnaire (QLQ-C30, version 1.0). Five domains were chosen a priori for analysis: global quality of life, physical, role and social functioning, and fatigue. In the phase II study, in which trastuzumab was given alone, there was no change in on-treatment QLQ-C30 scores compared with baseline. These results suggest that trastuzumab does not adversely affect HRQL during therapy. In the phase III study, the effects of trastuzumab plus chemotherapy were compared with those of chemotherapy alone. A comparison of QLQ-C30 scores during treatment did not show statistically significant differences between the two groups at the preset level of P = .01. However, comparison of on-treatment scores with baseline in patients receiving chemotherapy alone indicated mild worsening of physical and role functioning and of fatigue throughout the duration of treatment, whereas a similar comparison of those receiving chemotherapy with trastuzumab revealed mild worsening of role functioning at weeks 8 and 20 and of fatigue only at week 8. These results suggest that trastuzumab may be associated with an amelioration of the deleterious effects of chemotherapy alone. In summary, in the doses and schedules used in these studies, trastuzumab is not associated with worsening of HRQL.

The economic impact of the tacrine in the treatment of Alzheimer's disease.

Alzheimer's disease is a progressive neurodegenerative disorder that results in tremendous economic and quality-of-life burdens. This paper presents estimates of the impact of tacrine use on the costs of caring for patients with Alzheimer's disease. This study presents a cost analysis, based on a decision-analytic model constructed around the milestones in the progression of Alzheimer's disease. Clinical data concerning the effectiveness of tacrine came from published results of an open-label follow-up study of 663 patients originally enrolled in a placebo-controlled clinical trial of tacrine. Data concerning longevity, nursing home time, and costs of community and nursing home care are taken from several reports based on prospective cohorts of patients. The use of tacrine was associated with a cost savings of $9,250 (7.5%) over the patient's lifetime from diagnosis to death, even when averaged over data from patients who discontinued tacrine treatment or took only low doses. Most of the savings were due to reduced time in nursing homes. Patients who continued higher doses of tacrine experienced a cost saving of more than $36,500 over 5 years. Model results persisted over a wide range of sensitivity analysis variations. The use of tacrine for patients with mild-to-moderate Alzheimer's disease reduces the costs of medical and social services required for care, and it increases functioning and delays nursing home placement for up to 433 days. New treatments that can both improve clinical outcomes and save costs should be given serious consideration by clinicians and administrators.

The use of ketorolac in the management of postoperative pain.

Ketorolac tromethamine (Toradol) is a nonsteroidal antiinflammatory drug (NSAID) available in intramuscular (IM) and oral formulations for the management of acute pain. Intramuscular ketorolac is the only parenteral NSAID available for analgesic use in the US. The clinical profile is reviewed, and clinical studies most applicable to a postoperative patient are discussed in detail. The results of a clinical study performed at Emory University School of Medicine are presented. In this single-dose study, 176 patients received either 10 mg of oral ketorolac, 5 mg or 10 mg of IM morphine, or placebo after orthopedic surgery. The analgesic efficacy of ketorolac was comparable to both doses of morphine and significantly superior to placebo. Ketorolac, when administered intramuscularly or orally, is a safe and effective analgesic agent for the short-term management of acute postoperative pain and can be used as an alternative to opioid therapy.