A study of donepezil in female breast cancer survivors with self-reported cognitive dysfunction 1 to 5 years following adjuvant chemotherapy.

PURPOSE: Some breast cancer survivors report cognitive difficulties greater than 1 year after chemotherapy. Acetylcholinesterase inhibitors (AChEI) may improve cognitive impairment. We conducted a randomized, placebo-controlled, pilot study to assess the feasibility of using the AChEI, donepezil, to improve subjective and objective measures of cognitive function in breast cancer survivors. METHODS: Women who received adjuvant chemotherapy 1-5 years prior with current cognitive dysfunction symptoms were randomized to 5 mg of donepezil/day vs placebo for 6 weeks and if tolerated 10 mg/day for 18 weeks for a total of 24 weeks. A battery of validated measures of attention, memory, language, visuomotor skills, processing speed, executive function, and motor dexterity and speed was administered at baseline and at 24 and 36 weeks. Subjective cognitive function, fatigue, sleep, mood, and health-related quality of life were evaluated at baseline and at 12, 24, and 36 weeks. RESULTS: Sixty-two patients were enrolled, 76 % completed the study, self-reported compliance was 98 %, and toxicities were minimal. At the end of treatment, the donepezil group performed significantly better than the control group on two parameters of memory-the Hopkins Verbal Learning Test -Revised (HVLT-R) Total Recall (p = 0.033) and HVLT-R Discrimination (p = 0.036). There were no significant differences on other cognitive variables or in subjective cognitive function or quality of life. CONCLUSION: Accrual to this feasibility trial was robust, retention was good, compliance was excellent, and toxicities were minimal. IMPLICATIONS FOR CANCER SURVIVORS: Randomized clinical trials in breast cancer survivors to improve cognitive dysfunction are feasible. A phase III trial testing the efficacy of donepezil is warranted given these pilot results.

High-dose folinic acid and 5-fluorouracil in the treatment of advanced colon cancer.

Forty-eight patients with measurable metastatic colorectal cancer were treated with leucovorin (FA), 80 mg/m2 as an intravenous (i.v.) infusion over 20 h, followed by 5-fluorouracil (5-FU), 400 mg/m2, i.v. push on days 1-3. This same dose of FA was then administered as a 1-h infusion on day 11 and weekly thereafter, followed by 5-FU, 400 mg/m2, slow intravenous (i.v.) push. Thirty patients had received no prior chemotherapy, and 18 patients had received chemotherapy with various other regimens. The drugs were well tolerated, with minimal hematologic toxicity and mild to moderate gastrointestinal and mucosal toxicity. Three complete responses (CRs) and nine partial responses (PRs) were observed. Nineteen additional patients remained stable for prolonged periods of time, and 12 patients continued to progress through treatment. The median survival for responders was 52.5 weeks. The patients who had received prior chemotherapy had lower response rates than the previously untreated patients, but responses were seen in both subsets. The CR plus PR rate in previously untreated patients was 30%, with 40% having stabilization of disease. The CR plus PR rate in patients previously treated with other chemotherapy regimens was 19%, with an additional 50% having stabilization of disease. Patients with stable disease appeared to have a clinical benefit similar to that of patients with PR. Toxicity was generally mild and acceptable and consisted mainly of nausea, vomiting, and mucositis. At these dosage levels, diarrhea was not a limiting toxicity. CRs and PRs occurred only in patients with Eastern Cooperative Oncology Group (ECOG) performance status 1 and 2. Carcinoembryonic antigen (CEA) levels generally reflected the type of clinical response and could often predict responders early on in the course of treatment, but did not quantitatively correlate with the degree of response. This regimen has efficacy at least similar to that of standard 5-FU regimens, and appears to have activity as a "salvage therapy" also. The minimal toxicity of this regimen, its convenience for outpatient use, and the relatively low expense as compared with regimens employing a higher dose of FA recommend it for further investigation.

Evaluation of demand analgesia in a community hospital.

Since more than 60% of patients with cancer at some time will experience pain that requires medical or surgical intervention, pain control is an important priority for these patients. Demand analgesia literally places pain control in the hands of the patient. Based on their experience with patients who have used this system of pain treatment, the authors discuss the therapeutic advantages, economic considerations, and guidelines for use of patient-controlled analgesia.