SWOG-9510: evaluation of topotecan in hormone refractory prostate cancer: a Southwest Oncology Group study
Catherine E Klein1, Catherine M Tangen, Thomas J Braun
1University of Colorado, Denver, Colorado, USA. catherine.klein@med.va.gov
Background:
Prostate cancer is the most common malignancy in American men, and as many as 70% of those initially treated for localized disease will ultimately progress and be considered candidates to receive therapy for metastatic cancer [Fuks et al.: Int J Radiat Oncol Bio Phys 21:537-547, 1991; Chodak et al.: N Engl J Med 330:246-248, 1994]. Although most will respond initially to hormone manipulation, essentially all will fail and require additional therapy. No standard chemotherapy approach has been shown to prolong survival significantly, and new agents are desperately needed. Topotecan is a new topoisomerase-1 inhibitor whose early investigation suggested possible activity in hormone-refractory prostate cancer.
Methods:
In this phase II trial, patients having failed one or two prior androgen ablative therapies were treated with 21-day continuous intravenous infusions of topotecan at a dose of 0.5 mg/m(2) per day every 28 days.
Results:
Twenty-six eligible patients were entered on the study. There were no confirmed tumor responses. Median survival was 9 months. The most common toxicities were hematologic, with 8 of 24 assessable patients experiencing grade 4 toxicity.
Conclusion:
Topotecan infusions at this dose are ineffective in the management of hormone-refractory prostate cancer.
Insights
This study found that topotecan infusions are ineffective for treating hormone-refractory prostate cancer. The new agent did not show tumor responses and had significant hematologic toxicities in patients with advanced prostate cancer.
Area of Science:
- Oncology
- Medical Oncology
- Prostate Cancer Research
Background:
- Prostate cancer is a leading malignancy in men, often progressing to metastatic disease.
- Hormone therapy is a common initial treatment, but resistance eventually develops.
- There is a critical need for novel therapeutic agents for advanced prostate cancer.
Purpose of the Study:
- To evaluate the efficacy and safety of topotecan in patients with hormone-refractory prostate cancer.
- To determine if topotecan can provide a clinical benefit in patients who have failed prior androgen deprivation therapies.
Main Methods:
- A Phase II clinical trial was conducted.
- Patients received continuous intravenous infusions of topotecan at 0.5 mg/m(2)/day for 21 days every 28 days.
- Eligibility criteria included failure of one or two prior androgen ablative therapies.
Main Results:
- Twenty-six patients were enrolled; no confirmed tumor responses were observed.
- The median survival for the study population was 9 months.
- Hematologic toxicity was the most common adverse event, with 8 of 24 assessable patients experiencing Grade 4 toxicity.
Conclusions:
- Topotecan, administered as a continuous intravenous infusion at the tested dose, is ineffective for managing hormone-refractory prostate cancer.
- The observed toxicities, particularly hematologic, raise concerns about the tolerability of this regimen.
- Further investigation into topotecan for prostate cancer is not supported by these findings.
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