The outcome of Trabeculectomy with Mitomycin C at the Queen Elizabeth Hospital, Barbados

AIM: To evaluate the efficacy of trabeculectomy with mitomycin-c in a predominantly black population. METHOD: The records of 43 eyes with 34 patients (males 15, females 19; age range 22-87 years), who underwent trabeculectomies with mitomycin-c for uncontrolled glaucoma at the Queen Elizabeth Hospital were reviewed. Forty-three eyes (rt eyes 22, Lt eyes 21, unilateral 25, bilateral 9, combined procedure 4) had trabeculectomies. All surgeries were performed by six surgeons between July 1995 and October 1998. The concentration of mitomycin-c varied from 0.2 to 0.5 mg/ml and was applied over 2 to 5 minutes. RESULTS: We evaluated treatment outcome based on the following categories of surgical results for patients with a pre-operative IOP>21mmHg. 1. The operation was considered successful when the IOP was <21mmHg without any anti-glaucoma medications. 2. The operation was a failure when the IOP was raised >21mmHg and required anti-glaucoma medications to control the IOP. The mean preoperative IOP was 26mmHg and the mean postoperative IOP was reduced to 14mmHG. There was failure in 19 eyes where the IOP was raised over >21mmHg and required anti-glaucoma medications or control. Twenty-four eyes were still functional at 18 months with IOPs less than 21mmHg without any anti-glaucoma medications. Visual acuity (VA) in the functional 24 eyes: the VA remained the same in 9 patients and the VA progressively deteriorated in the remaining 15 patients in spite of reduced IOP after mitomycin trabeculectomies. CONCLUSION: The most common cause of failure after trabeculectomy is scarring at the filtration site due to fibrosis or more appropriately normal healing by fibrosis - mitomycin simply delayed the normal healing. Eyes with pseudopakia are at higher risk for failure. Most of the studies in the past were done in the predominantly white population with a short follow-up period. In contrast, all the patients in this study were of African origin and had at least 18 months follow-up, with mean follow-up of 39 months. To our knowledge, this is one of the longest follow-up studies in a predominantly Black population and is the first in the Caribbean. (AU)

Treatment of patients with advanced colorectal carcinomas with fluorouracil alone, high-dose leucovorin plus fluorouracil, or sequential methotrexate, fluorouracil, and leucovorin: a randomized trial of the Northern California Oncology Group.

We compared the effectiveness of fluorouracil (5-FU) alone (arm A), high-dose leucovorin plus 5-FU (arm B), and sequential methotrexate, 5-FU, and leucovorin (arm C) for treatment of patients with advanced colorectal carcinomas who had not received prior chemotherapy. Arm A consisted of infusions of 5-FU at 12 mg/kg/d intravenously (IV) for 5 days followed by weekly infusions of 5-FU at 15 mg/kg; arm B consisted of leucovorin infusions at 200 mg/m2/d IV plus infusions of 5-FU at 400 mg/m2/d IV on days 1 through 5 of a 28-day cycle; arm C consisted of methotrexate at 50 mg/m2 orally every 6 hours for five doses followed by infusions of 5-FU, 500 mg/m2 IV, and leucovorin, 10 mg/m2 orally, every 6 hours for five doses every other week. A total of 265 patients were entered into the trial, of whom 249 (94%) were fully evaluable. The objective response rate (complete [CR] plus partial [PR] responses) was 17.3% on arm A, 18.8% on arm B, and 19.8% on arm C (log-rank test, P greater than .4). The median time to failure was 138 days on arm A, 166 days on arm B, and 182 days on arm C (log-rank test, P values of arm A v B = .06; arm A v arm C = .04). Median survival was 345 days on arm A, 324 days on arm B, and 356 days on arm C (log-rank test, P greater than .4). Treatment with 5-FU alone was significantly more dose intensive and more toxic than either of the experimental combinations. The rates of grade 3 or greater nonhematologic toxicity were 42.3% on arm A, 24.3% on arm B, and 14.3% on arm C. Hematologic toxicity was milder but had the same pattern. This study indicates that these regimens of high-dose leucovorin plus 5-FU and sequential methotrexate, 5-FU, and leucovorin are not more effective than is 5-FU alone for treatment of patients with colorectal carcinomas when 5-FU is administered at high-dose intensity.

Chemoendocrine therapy with prolonged estrogen priming in advanced breast cancer: endocrine pharmacokinetics and toxicity.

Recent efforts to improve response rates in advanced breast cancer have used short, alternating courses of antiestrogen therapy followed by estrogen priming to cytokinetically enhance tumor cell sensitivity to antimetabolites. Based on recent in vitro and in vivo studies, we have introduced a chemoendocrine regimen that uses prolonged courses of estrogen priming. The present protocol consists of alternating monthly cycles of tamoxifen (TAM) and estradiol during which sequential (24-hr) methotrexate, 5-fluorouracil, and leucovorin are administered at 2-week intervals. Twenty-five patients with metastatic breast cancer received greater than 80 endocrine cycles and greater than 300 courses of chemotherapy by this protocol; two-thirds of these patients had previously failed other endocrine or chemotherapy regimens. Most patients experienced grade 1 or 2 myelosuppression or gastrointestinal symptoms during at least one treatment cycle; however, overall toxicity was considered to be mild and therapy was very well tolerated. Serum levels of estradiol, estrone, TAM, and TAM metabolites were measured during all phases of the endocrine cycle in five patients on chronic therapy. Concentrations of TAM and its more abundant metabolite, N-desmethyltamoxifen (N-desTAM), rose twofold during antiestrogen therapy and fell during estrogen priming, with mean levels persisting greater than 100 ng/ml throughout the priming interval. Mean estradiol (E2) and estrone (E1) levels rose during priming and were sustained fivefold and tenfold above the basal postmenopausal levels measured during antiestrogen treatment. Calculating the serum molar ratios of [TAM + N-desTAM]/[E2 + E1] during each phase of the treatment cycle confirmed that estrogen priming was achieved pharmacologically by this endocrine schedule. Clinical remissions were observed in this small patient sample with seven of 18 patients achieving either complete (28%) or partial (11%) responses, and an additional 39% obtaining disease stabilization. Further clinical study is necessary to evaluate the optimal response rate of this regimen and to determine whether cyclic estrogen priming by this schedule results in enhanced tumor cell proliferation in vivo.

Chemotherapy of unresectable or recurrent metastatic malignant melanomas: an update.

Satisfactory chemotherapeutic management of malignant melanomas in advanced stages must await development of more active agents and combinations of them than are presently available. The development of entirely new means of treatment by hormones, heat, and adjuvants like amphotericin B may improve the efficacy of currently available agents.