Combination of epirubicin and cisplatin in hormone-refractory metastatic prostate cancer.

Anthracyclines and cisplatin have been shown separately to have modest activity in prostate cancer. The synergism between anthracyclines and cisplatin, with the lack of overlapping toxicities, led to the conduct of this phase II trial of the combination of epirubicin and cisplatin in hormone-refractory metastatic prostate cancer. Twenty-one evaluable patients with hormone-refractory metastatic prostate cancer received epirubicin 100 mg/m2 followed by cisplatin 80 mg/m2 with prehydration and mannitol diuresis. Epirubicin and cisplatin produced a biochemical response (>50% decrease in tumor marker) in 32% of patients, symptomatic improvement in 38%, and a response in measurable and evaluable disease sites in 14%. Toxicities were mainly hematologic, with 77% and 41% >grade 2 neutropenia and thrombocytopenia, respectively. Greater than grade 2 toxicities were: cardiac (three), renal secondary to sepsis (one), nausea and vomiting (two), weakness (one), mucositis (one), and diarrhea (one). The combination of epirubicin and cisplatin was associated with manageable toxicities in this elderly population; however, antitumor activity was marginal in this disease. Participation in clinical trials should continue to be offered to patients with hormone-refractory metastatic prostate cancer.

Results from the Ontario breast screening program, 1990-1995.

OBJECTIVE: The Ontario breast screening program (OBSP) is a provincial breast screening programme offering two view mammography, clinical breast examination, instruction in breast self examination, and systematic two year recall to Ontario women 50 years and older. This paper presents the results of the programme's intermediate outcomes from 1990 to 1995 and compares them with recommended standards and other published programmes. METHODS: Programme data from a provincial screening programme in a large Canadian province were collated from 18 sites in operation between July 1990 and December 1995. RESULTS: In its first five years of operation, 215,738 screens were performed on 142,173 women. The referral rates for initial and rescreens are 13.8% and 8.6% respectively. A total of 1718 women were diagnosed with cancer, 1325 at initial screens and 393 at rescreens, resulting in cancer detection rates of 9.3 and 5.3/1000. The cancer detection rates for invasive cancers were 8.3/1000 at initial screens and 4.5/1000 at rescreens. The benign to malignant biopsy ratio was 1.5:1 at initial screens and 1.3:1 at rescreens. Of the 1358 cancers diagnosed at initial screens, 11.6% were in situ and 50.3% of invasive cancers of known size were < 15 mm. For women with invasive cancer where nodal status was known, 71.3% were node negative. The proportions at rescreens were 15.7%, 60.0%, and 76.0% respectively. CONCLUSIONS: While the OBSP has achieved the standards suggested by other studies and programmes during its first five years of operation, there is work to be done to increase participation and obtain more complete data on tumour size and nodal status.

Changes in women's breast cancer screening practices, knowledge, and attitudes in Ottawa-Carleton since 1991.

Although Canadian Breast Screening Guidelines have been in place since 1988, participation rates have been suboptimal. The study objective was to describe changes in breast screening knowledge, attitudes, and practices among women aged 50 to 69 years since initiation of a regional mass screening program in Ottawa-Carleton in 1991. A random-digit-dialing telephone survey was conducted with 384 women aged 50 to 69 years residing in Ottawa-Carleton and compared to a 1991 survey. Between 1991 and 1994 there were significant increases in the percentage ever having had a mammogram (from 60% to 83%) and monthly breast self-examination (from 46% to 54%). Professional breast examination rates were unchanged as were overall attitudes and concerns about screening. There were significant improvements in knowledge and encouragement to have a mammogram. As the focus on primary health care within our health care system grows, and as service delivery changes, we must continue to search for, and continually evaluate, innovative strategies to align practices with Canadian breast screening recommendations.

A phase II study of 5-fluorouracil and high dose folinic acid in cisplatin-refractory metastatic bladder cancer.

BACKGROUND: Bladder cancer is a chemosensitive tumour, however, there is no effective therapy for patients with metastatic disease who failed to respond or relapsed after prior treatment with cisplatin-based chemotherapy. Single agent 5-fluorouracil has modest activity in bladder cancer. The combination of 5-fluorouracil with folinic acid results in stabilization of the ternary complex of 5-fluorodeoxyuridine monophosphate-thymidylate synthetase-5,10 methylene tetrahydrofolate leading to increased DNA inhibition and increased cytotoxicity of 5-fluorouracil. PATIENTS AND METHODS: Fourteen evaluable patients with metastatic bladder cancer were treated with 5-fluorouracil at 300 mg/m2 and folinic acid at 200 mg/m2 daily for five days. RESULTS: There were no complete or partial responses. One patient had a minor response and three patients had stable disease. Diarrhea and mucositis occurred in 25% of patients. There was one treatment-related death. CONCLUSION: High dose folinic acid did not increase the cytotoxicity of 5-fluorouracil in metastatic bladder cancer after cisplatin failure.

5-fluorouracil and high dose folinic acid in hormone-refractory metastatic prostate cancer: a phase II study.

BACKGROUND: The response of hormone-refractory metastatic prostate cancer to chemotherapy is poor. The antitumour activity of single agent 5-fluorouracil (5-FU) is approximately 15%. Folinic acid is a reduced folate which when combined with 5-FU augments the activity of 5-FU by stabilizing the ternary complex of 5-deoxyuridine monophosphate-thymidylate synthetase-5,10 methylene tetrahydrofolate, resulting in increased DNA inhibition and in increased cytotoxicity of 5-FU. PATIENTS AND METHODS: We used the combination of 5-FU at 300-370 mg/m2 and folinic acid at 200 mg/m2 daily for five days in 16 patients with hormone-refractory metastatic prostate cancer. RESULTS: A total of 15 evaluable patients were treated. There were no complete or partial responses. Seven patients had stable disease. Diarrhea constituted the most common non-hematologic toxicities (67%). Four patients experienced grade 3 and 4 neutrophil toxicity. There was one treatment-related death from an acute enterocolitis and peritonitis in a patient with grade 4 neutropenia. CONCLUSION: High dose folinic acid did not increase the cytotoxicity of 5-FU in hormone-refractory metastatic prostate cancer.

Phase I study of oral menogaril administered daily for 14 consecutive days.

Twenty-eight patients were treated with oral menogaril daily x 14 every 4 weeks. Granulocytopenia was dose-limiting at 50-60 mg/m2 per day. Neutropenic fever occurred in one patient. Thrombocytopenia occurred in 3 of 6 patients treated with menogaril 60 mg/m2/day. Nausea and vomiting and other toxic effects were generally mild. No cardiac toxicity was seen. One partial remission and three minor responses were noted among 11 previously treated patients with carcinoma of the bladder. One minor response was noted among 3 patients with colorectal cancer. The dose recommended for phase II studies is 50 mg/m2 per day for 14 days. Phase II studies are recommended in carcinoma of the bladder. Gastrointestinal toxicity is substantially less on this schedule than with oral menogaril administered on a weekly or q4wk schedule, but thrombocytopenia may be more common.

Phase I study of intracarotid administration of carboplatin.

Fifteen patients were treated in a Phase I study of intracarotid carboplatin (200-400 mg/m2) in 5% dextrose and water infused over 15 to 30 minutes through a transfemoral catheter with a 0.2-micron inline filter. This study was done because intravenous carboplatin has less neurotoxicity than cisplatin and is active against brain tumors. Eleven men and four women ranging in age from 37 to 72 years (median, 59 years) were treated. The Eastern Cooperative Oncology Group performance status was 1 in 3, 2 in 4, and 3-4 in 8 patients. Eight patients had one to three previous chemotherapy regimens; previous radiotherapy had failed in 13 patients. The response of patients in the Phase I study follows: glioblastoma, 6 failed; not evaluated because of early death from pulmonary embolus, 1; recurrent Grade II and III glioma, 1 stable (minor response with neurologic improvement) and 2 failed; malignant oligodendroglioma, 1 failed; brain metastases from nonsmall cell lung cancer, 1 partial remission, 1 stable (minor response), and 1 failed; brain metastases from unknown primary, 1 stable (minor response with neurological improvement). Median survival was 9 weeks. Nausea was mild to moderate. One patient had granulocytopenia, and 2 had thrombocytopenia (mild). At 200 mg/m2 (2 patients), 1 had a focal seizure. At 300 mg/m2 (9 patients), 2 with abnormally small arteries had severe pain early in the treatment and posttreatment ipsilateral conjunctival edema, decreased vision, and cerebral edema (with partially reversible increased hemiparesis); 1 other had mild decrease in ipsilateral vision and 1 had transient aphasia on removal of the catheter (possibly the result of a vascular spasm).(ABSTRACT TRUNCATED AT 250 WORDS)

5-Fluorouracil with folinic acid is not effective against metastatic adenocarcinoma of the lung.

Thirty patients with a diagnosis of metastatic adenocarcinoma of the lung were entered on a trial to evaluate the antitumor efficacy of 5-fluorouracil 370 mg/m2 daily for 5 days every four weeks in combination with folinic acid 200 mg/m2, 60 min prior to 5FU. All patients had a good performance status, bidimensionally measurable disease, and weight loss less than or equal to 5% of preillness weight. Of the 29 evaluable patients, only two (7%) had partial responses (95% confidence limits 1-24%). Eleven (38%) had stable disease and 16 (55%) progressed. The two responding patients survived 12 and 60+ weeks. The median survival of all evaluable patients was 25 weeks (range 7-60+) and that of the stable patients was 26 weeks. The principal toxicities observed were diarrhea and stomatitis. Myelosuppression was rarely dose limiting. In contrast to the results of treatment with 5FU and folinic acid in metastatic colorectal cancer and breast cancer, the results of treatment with this combination of agents have been much less encouraging in adenocarcinoma of the lung.