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Phase II evaluation of coumarin (1,2-benzopyrone) in metastatic prostatic carcinoma
J L Mohler1, L G Gomella, E D Crawford
1Division of Urology, University of North Carolina, Chapel Hill 27599-7235.
Abstract:
The unavailability of effective treatment of metastatic hormone refractory prostatic carcinoma warrants trials of new and promising treatments. Coumarin is an investigational new drug that has produced objective tumor regression in some patients with metastatic renal cell carcinoma and malignant melanoma. Coumarin has shown activity against prostatic carcinoma in the Dunning R-3327 rat prostatic adenocarcinoma model. Forty-eight patients with metastatic hormone naive (5 stage D1 and 10 stage D2) or hormone refractory (33 stage D3) prostatic carcinoma of average age 67.6 years (range 46-86) and ECOG performance status of 2 or better were given 3 grams coumarin daily by mouth and evaluated monthly for toxicity and response by rigid criteria in a multicenter trial. Toxicity was limited to asymptomatic SGOT elevations in 3 patients and nausea and vomiting in 4 patients that required cessation of therapy in 2. Eligibility and protocol violations removed 6 additional patients from response evaluation. There were no complete responses. Partial responses (3 of 40 patients, 8%) occurred in 2 patients with bidimentionally measurable disease and 1 patient with disease evaluable by bone scan and elevated prostate specific antigen and prostatic acid phosphatase. The remaining patients progressed after 1 to 12 (average 4.4) months. Coumarin is a relatively nontoxic drug that may warrant further trials in a subset of patients with prostatic carcinoma.
Insights
Coumarin showed limited efficacy in treating advanced prostate cancer, with 8% partial response rate. Further trials may be warranted in specific patient groups due to its low toxicity.
Area of Science:
- Oncology
- Pharmacology
Background:
- Metastatic hormone-refractory prostate carcinoma lacks effective treatments, necessitating novel therapeutic approaches.
- Coumarin, an investigational drug, has demonstrated tumor regression in metastatic renal cell carcinoma and melanoma.
- Preclinical studies indicated coumarin's activity against prostate carcinoma in the Dunning R-3327 rat model.
Observation:
- A multicenter trial evaluated coumarin's efficacy and toxicity in 48 patients with metastatic prostate carcinoma (hormone-naive or refractory).
- Patients received 3 grams of coumarin daily, with monthly assessments for toxicity and response.
- Toxicity was generally mild, including asymptomatic SGOT elevations and nausea/vomiting.
Findings:
- No complete responses were observed in the trial.
- Partial responses (8%) were achieved in 3 out of 40 evaluable patients with measurable or evaluable disease.
- The majority of patients experienced disease progression within an average of 4.4 months.
Implications:
- Coumarin exhibits a favorable toxicity profile, suggesting its potential as a relatively safe agent.
- Further investigation of coumarin in specific subsets of prostate cancer patients may be warranted.
- The limited efficacy observed necessitates the development of more potent therapeutic strategies for advanced prostate cancer.