Vinorelbine-Docetaxel for Advanced Prostate Cancer: A Doublet Worth Exploring
Vinorelbine-Docetaxel for Advanced Prostate Cancer: A Doublet Worth Exploring
Abstract & Commentary
Synopsis: The management of advanced, hormone-resistant prostate cancer remains challenging. In a Phase II trial conducted under the auspices of the Boca Raton Comprehensive Cancer Center, 21 patients received vinorelbine (20 mg/m2) and docetaxel (25 mg/m2) on days 1 and 8 of a 21-day cycle. PSA levels fell in the majority of patients, and the combination was generally well tolerated. This particular combination deserves further investigation.
Source: Koletsky AJ, et al. Cancer J. 2003;9:286-292.
Hormone refractory prostate cancer has been a challenge as effective, nontoxic therapy remains elusive. In the current report, the combination of low-dose docetaxel (25 mg/m2) and vinorelbine (20 mg/m2) was investigated to examine the therapeutic synergy of these agents. The doses chosen for the trial were based upon phase I results in non-small-cell lung cancer.1 At the selected doses, this prior experience would predict minimal toxicity and a low risk for schedule delays.
Patients with histologically confirmed hormone-refractory prostate cancer were eligible for the study. To enroll, patients needed a Karnofsky performance status of > 70 and evidence for adequate bone marrow reserve. It was a single-arm study in which all patients received vinorelbine (20 mg/m2) followed by docetaxel (25 mg/m2) on days 1 and 8 of a 21-day cycle. Tumor response was defined by reductions from baseline prostate-specific antigen (PSA) or bidimensionally measurable disease. Twenty-one patients were enrolled. The mean age was 76 years (range, 60-83 years) and the median PSA level was 116 ng/mL (range, 10.4-4262). The median number of courses of therapy was 7.5. Of the 19 patients who were evaluable for biochemical response, PSA reductions from baseline of > 75% were observed in 8; PSA reductions > 50% to £ 75% were observed in 3; and < 50% were observed in 7 patients. The median PSA decrease was 60% ± 31%. Of 5 patients with measurable disease, 3 were evaluable and of these, 1 had a complete response and 2 had partial responses.
The vinorelbine/docetaxel doublet was generally well tolerated. In the first 2 cycles of therapy, 6 patients had grade 3 and 8 patients had grade 4 neutropenia, and all patients were manageable with granulocyte colony stimulating factor support. The great majority of patients were able to proceed through treatment without dose or schedule alterations.
Comment by William B. Ershler, MD
Prostate cancer is the most prevalent malignancy in men; and once the disease becomes refractory to hormonal manipulation, tumor-directed therapy has provided little with regard to tumor regression, quality of life, or overall survival. This cannot be entirely attributed to insensitivity to chemotherapy, because a number of drugs (including docetaxel and vinorelbine) have demonstrated single-agent activity. One clear problem is that clinical trials have proven difficult to conduct. The patients are generally older, treated in the community, and oftentimes primarily managed by urologists who, when the disease becomes hormone refractory, are just as likely to refer to hospice for supportive care as they are to a medical oncologist for chemotherapy.
The report by Koletsky and colleagues is a refreshing contribution. Although limited in number, the trial is an excellent example of the kind of research that can and should be done in the community when dealing with older patients with advanced disease. To their credit, the average age on study was 76 years and all patients had metastatic disease. The chemotherapy program was chosen astutely, and the schedule (that basically calls for weekly visits) was one that is very manageable for geriatric outpatients. Furthermore, the finding of a biochemical response in the majority of patients and a complete response in 1 of 3 with measurable disease offers further encouragement to the more detailed investigation of this particular doublet in the management of advanced prostate cancer. What is needed is a large-scale, multisite, community-based trial in which this doublet is compared with either agent alone, or best supportive care, with outcomes to include quality-of-life measures as well as tumor response rates and survival. The success of this would of course rely on collaborative arrangements with urologic oncologists, and it is encouraging to note that at least a few such studies are either underway or in the late planning stages.
Dr. Ershler, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC.
Reference
1. Johnston E, et al. Proc Am Soc Clin Oncol. 1998;18: 476a.
The management of advanced, hormone-resistant prostate cancer remains challenging.Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.