Metastatic Androgen-independent Prostate Cancer Research Articles

Estramustine, zoledronic acid and weekly docetaxel in metastatic androgen independent prostate cancer (MAIP)

4706 Background: Docetaxel and estramustine phosphate have been shown to have synergistic and significant activity in patients with MAIP. Zoledronic acid is a third generation biphosphonate, which reduces skeletal events by inhibiting bone destruction in MAIP patients. Methods: We conducted a phase II trial with the combination of estramustine, zoledronic acid and weekly docetaxel. Eligibility consisted of metastatic prostate adenocarcinoma with objective progression or rising prostate specific antigen (PSA) levels despite androgen deprivation therapy. Prior chemotherapy was not allowed; radiation was permitted. A PS of £ 2, adequate bone marrow, hepatic, renal and cardiac functions were required. Estramustine was administered orally at a dose of 140mg three times daily on days 1 to 21 on a 28-day cycle. 25mg/m2 of docetaxel was administered intravenously on days 1,8 and 15 of each cycle. Zoledronic acid was given at a dose of 4mg in 15 minutes infusion on D1 of each cycle. Results: Between March 2002 and October 2003, 24 patients (pts) were enrolled. Median age was 71 years [range 53–83y]. 20 pts had only bone metastases and 4 pts had measurable disease. One hundred and four cycles of therapy have been delivered with a median of four cycles per patient, [range 1–7]. Predominant toxicities consisted of: grades II-III anemia (20.8%), grades III thrombocytopenia (4.1%), fatigue (20.8%), grades II-III alopecia (12.5%), and severe hypocalcaemia (8.3%). 2 pts presented Deep Venous Thrombosis with deadly pulmonary embolism. One patient died from Stevens Johnson syndrome and grade IV hepatic toxicity at D15 of cycle 2. 22 pts were evaluable for response. 12 pts (54.5%) had biological response (> 50% PSA decline) which lasted from 5 to 63 weeks. 2 among the 4 measurable disease pts had objective response. 12 pts experienced clinical benefit with pain reduction. Conclusion: This combination is well tolerable, effective and worthy to be proposed as a standard therapy for MAIP. No significant financial relationships to disclose.

How good is physician reporting of chemotherapy adverse effects? A comparison to patient-reported symptoms from the QLQ-C30

8022 Background: Adverse effects in chemotherapy clinical trials are assessed and reported by physicians, yet physicians' accuracy in assessing symptoms has been questioned. We compared patient reporting of 8 symptoms using a validated quality of life instrument, the EORTC QLQ-C30 (QLQ) with a physician's reporting of the same symptoms in the study's adverse events log. Methods: Men with metastatic androgen independent prostate cancer enrolled in a phase II trial of weekly calcitriol and docetaxel completed the QLQ every 4 weeks and saw the treating physician on the same schedule. A patient reported symptom was considered present if the QLQ score increased by at least 10 points (0–100 scale) for at least 4 weeks. A physician reported symptom was considered present if it was ever documented in the adverse event log. Concordance was assessed using Kappa and physician sensitivity and specificity were calculated using QLQ as the standard. Assuming that false positives much less likely than false negatives, imputed incidence was calculated by counting a symptom as new or worsened if it was positive according to either the QLQ or the physician. Results: Thirty-seven men were observed on treatment for up to 28 weeks of chemotherapy for this analysis. Compliance with QLQ questionnaires was 94%, thus 283 QLQs were analyzed. Using QLQ as the standard, the physician missed 50/104 (48%) of symptoms. Conclusions: Even in the context of a tightly controlled single-institution clinical trial and a principal investigator who was aware that his practice was being scrutinized, physician reporting of common chemotherapy adverse events lacked sensitivity and correlated poorly with a validated instrument. Tools for collecting patient-reported adverse event data in chemotherapy clinical trials should be developed. No significant financial relationships to disclose.

High-Dose calcitriol, docetaxel, and estramustine in androgen-independent prostate cancer (AIPC): A phase I/II study

4678 Background: Phase II studies suggest that the clinical activity of docetaxel in AIPC may be increased by the addition of estramustine or high dose calcitriol. We sought to test the safety of a 3-drug regimen that combined docetaxel with estramustine and calcitriol. Methods: Patients with metastatic AIPC received calcitriol 60 mcg PO over 4 hours (15 mcg hourly for 4 doses) on day 1, dexamethasone 8 mg PO BID on days 1–3, estramustine 280 mg PO TID on days 1–5, and docetaxel 60 mg/m2 (70 mg/m2 starting in cycle 2 if no ≥ grade 3 toxicity during cycle 1) IV over 60 min on day 2. Treatment was repeated every 21 days for up to 12 cycles. Patients received aspirin 325 mg and warfarin 1 or 2 mg PO daily. Calcium supplements were prohibited within 7 days of calcitriol dosing and increased oral hydration on days 1–3 was recommended. A dose de-escalation scheme for calcitriol was planned if dose limiting toxicities were encountered during the first cycle of treatment in > 1/3 of patients. Results: 20 patients were enrolled between January and October 2003. 8 patients were chemotherapy-naïve and 12 had received prior docetaxel-based therapy (5 received more than 1 prior chemotherapy regimen). The regimen was generally well tolerated and criteria for dose de-escalation were not met. Treatment-related ≥ Grade 3 toxicity included: Hypophosphatemia- 4, Neutropenic fever - 2, perforated diverticulum - 1, edema - 1, vomiting - 1, ALT elevation - 1, anemia - 1, PTT elevation –1. 3 patients had thromboembolic complications and one patient had grade 3 hematuria thought to be due to tumor. Hypercalcemia was seen in 4 patients (1 grade 2, 3 grade 1). 17 patients are evaluable for PSA response at this time. 4 of 7 chemotherapy-naïve patients (57%) met criteria for PSA response (confirmed ≥ 50% decline). 1 of 7 patients (14%) treated with 1 prior docetaxel-containing regimen met these criteria. There were no responses among the 3 patients treated with more than 1 prior chemotherapy regimen. Conclusions: High-dose calcitriol may be safely added to docetaxel and estramustine administered on a 21-day schedule. Additional studies will further define the role of this regimen in AIPC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Pharmaceuticals

Novel therapeutic strategies for androgen-independent prostate cancer: An update

Close to 30,000 men will die from prostate cancer in the United States in 2003. Hormonal ablation, the basis of systemic therapy, will invariably fail to control the progression of metastatic prostate cancer in the long run. For many years the only available therapeutic modalities for patients with metastatic androgen independent prostate cancer have been second-line hormonal maneuvers with estrogens or steroids and chemotherapy. So far, chemotherapy has been shown to confer adequate palliation but no overall survival benefit in prospective randomized controlled trials, and the only chemotherapy drugs approved by the US Food and Drug Administration are mitoxantrone and estramustine. Novel treatment strategies that aim at specific signaling pathways, apoptosis, differentiation, or specific membranous targets are being developed. Such new therapeutic modalities, along with recent data on immunotherapy and bone targeting strategies, will be reviewed here.

Phase Ii Study of Cyclophosphamide, Etoposide and Estramustine (Cee) in Metastatic Androgen Independent Prostate Cancer (Aipc)

Phase Ii Study of Cyclophosphamide, Etoposide and Estramustine (Cee) in Metastatic Androgen Independent Prostate Cancer (Aipc)

604 Nadir prostatic specific antigen as a predictor of progression to androgen independent metastatic prostate cancer

604 Nadir prostatic specific antigen as a predictor of progression to androgen independent metastatic prostate cancer

Weekly Docetaxel in Elderly Patients with Prostate Cancer: Efficacy and Toxicity in Patients Aged ≥ 70 Years Compared with Patients Aged < 70 Years

We sought to determine whether age was significantly associated with efficacy and toxicity of weekly docetaxel in patients with metastatic androgen-independent prostate cancer (AIPC). Individual patient ata were pooled from 2 phase II clinical trials of weekly docetaxel 36 mg/m2 for 6 of every 8 weeks in men with metastatic AIPC. Baseline characteristics and outcome measures of men ≥ 70 years of age (n = 52) were compared with patients < 70 of age (n = 34) using Pearson χ2 test for categorical variables, Mann-Whitney U test for continuous variables, and log-rank test of Kaplan-Meier estimates for time-dependent variable. Multivariate analysis was used to adjust for any imbalances in baseline characteristics. At baseline, older patients had a lower hemoglobin level (P = 0.05) and a higher serum prostate-specific antigen (PSA; P = 0.04). The PSA response rate was 47% (95% CI, 33%–62%) in older patients and 40% (95% CI, 23%–59%) in younger patients (P = 0.75). Similarly, measurable disease response rate (P = 0.43), time to progression (P = 0.28), and survival (P = 0.52) were not affected by age in both univariate and multivariate analyses. There was also no difference in overall hematologic and nonhematologic toxicity ≥ grade 2. This comparison of pooled individual patient data from 2 phase II studies of weekly docetaxel in AIPC did not reveal significant differences in efficacy or toxicity in men aged ≥ 70 years compared with younger patients. These findings are consistent with the hypothesis that docetaxel chemotherapy in patients with AIPC is equally well tolerated and effective across a wide range of ages.

Weekly high-dose calcitriol and docetaxel in metastatic androgen-independent prostate cancer

Weekly high-dose calcitriol and docetaxel in metastatic androgen-independent prostate cancer

Increased frequency of venous thromboembolism with the combination of docetaxel and thalidomide in patients with metastatic androgen-independent prostate cancer.

To evaluate the frequency of venous thromboembolism (VTE) in patients with advanced androgen-independent prostate cancer who were treated with docetaxel alone or in combination with thalidomide. Retrospective analysis of a randomized phase II trial. National Institutes of Health clinical research center. Seventy men, aged 50-80 years, with advanced androgen-independent prostate cancer. Each patient received either intravenous docetaxel 30 mg/m2/week for 3 consecutive weeks, followed by 1 week off, or the combination of continuous oral thalidomide 200 mg every evening plus the same docetaxel regimen. This 4-week cycle was repeated until there was evidence of excessive toxicity or disease progression. None of 23 patients who received docetaxel alone developed VTE, whereas 9 of 47 patients (19%) who received docetaxel plus thalidomide developed VTE (p=0.025). The addition of thalidomide to docetaxel in the treatment of prostate cancer significantly increases the frequency of VTE. Clinicians should be aware of this potential complication when adding thalidomide to chemotherapeutic regimens.

A Phase I/II Study of High-Dose Tamoxifen in Combination with Vinblastine in Patients with Androgen-Independent Prostate Cancer

In this phase I/II clinical trial the antitumor activity of high-dose tamoxifen when administered in combination with vinblastine was assessed and the toxicity profile of this combination characterized. All 25 patients enrolled in this study were required to have androgen-independent prostate cancer and to maintain androgen ablation during treatment. Vinblastine was given by continuous infusion over 5 days. Doses were increased from 0.9 mg/m2/day to 1.5 mg/m2/day in successive cohorts of at least 3 patients, with no further escalation even in the absence of dose-limiting toxicity. Intra-patient dose escalation was permitted. Tamoxifen was administered at a dose of 200 mg/kg on day 1, then 120 mg/kg/day on day 2. Standard response criteria were utilized to assess antitumor activity and CTC toxicity criteria were used. Quality of life (QOL) pain assessments were evaluated at each visit to the clinic. Most patients tolerated the highest dose of vinblastine at 1.5 mg/m2/day by continuous infusion over 5 days with 200 mg/kg/day of tamoxifen on day 1 and day 2. One patient had a greater than 50% decline in prostate-specific antigen that lasted for 170 days. Two patients received dose reductions because of toxicity. The most common serious toxicities included neutropenia, and fatigue. Reversible neurosensory, neuromotor, neurocortical and neurocerebellar toxicities were reported. Six of the 25 patients enrolled in the study (24%) experienced reversible neurologic toxicity of at least grade III. No statistically significant differences between precycle assessment of QOL and subsequent cycles were observed. It is concluded that vinblastine at 1.5 mg/m2/day continuous IV infusion combined with tamoxifen 200 mg/kg/day on day 1 and day 2 is inactive, and not without toxicity in the treatment of advanced metastatic androgen-independent prostate cancer.

An active regimen of weekly paclitaxel and estramustine in metastatic androgen-independent prostate cancer

Objectives The efficacy of weekly high-dose paclitaxel in androgen-independent prostate carcinoma and its cytotoxic synergy with estramustine led to the evaluation of a weekly schedule of paclitaxel and estramustine in this Phase II trial. Methods Patients were eligible if they had metastatic prostate adenocarcinoma with objective progression or rising prostate-specific antigen (PSA) levels despite androgen deprivation therapy and antiandrogen withdrawal. Prior radiation and/or one prior chemotherapy regimen was permitted. A Zubrod performance status of 2 or less and adequate bone marrow and hepatic and renal function were required. Estramustine was administered orally at a dose of 280 mg three times daily on days 1 to 3, 8 to 10, and 15 to 17. Paclitaxel (150 mg/m 2) was administered as a 1-hour intravenous infusion on days 2, 9, and 16. Therapy was repeated every 28 days (one cycle). Results Twenty-eight patients were enrolled (median age 71.5 years). Fifteen patients had measurable disease (nine nodal and seven visceral) and 13 had bone-only metastases. A total of 116 cycles of therapy were delivered (median 4 cycles per patient, range 1 to 12). Nine patients required dose reduction. The predominant toxicities consisted of grade 3 neuropathy in 6 patients and grade 3 and 4 neutropenia in 4 patients, with one hospitalization for febrile neutropenia. Three patients had thrombotic manifestations: one deep venous thrombosis and two non-Q wave myocardial infarctions. Of the 28 patients, 26 were assessable for response. Of 13 patients with measurable disease, 5 demonstrated a partial response (1 in the liver and 4 in the lymph nodes), and 8 of 13 patients with bone-only metastases had a 50% or greater decrease in PSA level. Three patients had a 90% or greater decline in PSA. The overall PSA response rate was 61.53% (95% confidence interval 38.1% to 74.2%). The median time to progression was 4.64 months, and the median survival was 13 months. Conclusions The combination of weekly estramustine and paclitaxel is active in metastatic androgen-independent prostate cancer.

Prompt Resolution of Acute Disseminated Intravascular Coagulation With Docetaxel and Cisplatin in Hormone Refractory Prostate Cancer

No AccessJournal of UrologyCLINICAL UROLOGY: Case Reports1 Oct 2002Prompt Resolution of Acute Disseminated Intravascular Coagulation With Docetaxel and Cisplatin in Hormone Refractory Prostate Cancer C. Avancès, W. Jacot, P. Sénesse, and S. Culine C. AvancèsC. Avancès More articles by this author , W. JacotW. Jacot More articles by this author , P. SénesseP. Sénesse More articles by this author , and S. CulineS. Culine More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)64487-4AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Prompt Resolution of Acute Disseminated Intravascular Coagulation With Docetaxel and Cisplatin in Hormone Refractory Prostate Cancer." The Journal of Urology, 168(4 Part 1), p. 1496 References 1 : Successful use of Samarium 153 for emergency treatment of disseminated intravascular coagulation due to metastatic hormone refractory prostate cancer. J Urol2000; 164: 782. Link, Google Scholar 2 : Disseminated intravascular coagulation in a patient treated with strontium-89 for metastatic carcinoma of the prostate. Clin Nucl Med1999; 24: 852. Crossref, Medline, Google Scholar 3 : Successful treatment with mitoxantrone chemotherapy of acute disseminated intravascular coagulation due to metastatic androgen independent prostate cancer. J Urol2000; 163: 248. Link, Google Scholar From the Department of Medical Oncology, CRLC Val d’Aurelle, Montpellier, France© 2002 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited by Agrawal K, Agrawal N and Miles L (2019) Disseminated Intravascular Coagulation as an Initial Manifestation of Metastatic Prostate Cancer Emergently Treated with Docetaxel-Based ChemotherapyCase Reports in Oncological Medicine, 10.1155/2019/6092156, VOL. 2019, (1-6), Online publication date: 24-Apr-2019. Desai M, John B, Evans G and Eddy B (2015) Prostate cancer: beware of disseminated intravascular coagulationCase Reports, 10.1136/bcr-2014-206814, VOL. 2015, NO. mar27 1, (bcr2014206814-bcr2014206814), Online publication date: 27-Mar-2015. Ong S, Taverna J, Jokerst C, Enzler T, Hammode E, Rogowitz E, Green M and Babiker H (2015) Prostate Cancer-Associated Disseminated Intravascular Coagulation with Excessive Fibrinolysis Treated with DegarelixCase Reports in Oncological Medicine, 10.1155/2015/212543, VOL. 2015, (1-6), . Davison S, Kessler C and Al-Attar A (2009) Microvascular Free Flap Failure Caused by Unrecognized HypercoagulabilityPlastic and Reconstructive Surgery, 10.1097/PRS.0b013e3181adcf35, VOL. 124, NO. 2, (490-495), Online publication date: 1-Aug-2009. Chargari C, Vedrine L, Bauduceau O, Le Moulec S, Fayolle M, Ceccaldi B and Houlgatte A (2008) Cancer de prostate et coagulation intravasculaire disséminée : une revue de la littératureProgrès en Urologie, 10.1016/j.purol.2007.12.001, VOL. 18, NO. 1, (9-13), Online publication date: 1-Jan-2008. Pouessel D, Gallet B, Bibeau F, Avancès C, Iborra F, Sénesse P and Culine S (2007) Liver metastases in prostate carcinoma: clinical characteristics and outcomeBJU International, 10.1111/j.1464-410X.2006.06663.x, VOL. 99, NO. 4, (807-811), Online publication date: 1-Apr-2007. Duran I and Tannock I (2006) Disseminated Intravascular Coagulation as the Presenting Sign of Metastatic Prostate CancerJournal of General Internal Medicine, 10.1111/j.1525-1497.2006.00506.x, VOL. 21, NO. 11, (C6-C8), Online publication date: 1-Nov-2006. GULDBAKKE K and SCHANBACHER C (2006) Disseminated Intravascular Coagulation Unmasked by Mohs Micrographic SurgeryDermatologic Surgery, 10.1111/j.1524-4725.2006.32154.x, VOL. 32, NO. 5, (760-764), Online publication date: 1-May-2006. Bern M (2013) Coagulopathy, following medical therapy, for carcinoma of the prostateHematology, 10.1080/10245330410001701594, VOL. 10, NO. 1, (65-68), Online publication date: 1-Feb-2005. Volume 168Issue 4 Part 1October 2002Page: 1496 Advertisement Copyright & Permissions© 2002 by American Urological Association, Inc.Keywordsdisseminated intravascular coagulationprostatic neoplasmsdrug therapycisplatinMetricsAuthor Information C. Avancès More articles by this author W. Jacot More articles by this author P. Sénesse More articles by this author S. Culine More articles by this author Expand All Advertisement PDF downloadLoading ...

Effects of docetaxel on pain due to metastatic androgen-independent prostate cancer.

Bone pain commonly plagues patients with metastatic androgen-independent prostate cancer. Studies of mitoxantrone demonstrated that chemotherapy can substantially reduce this debilitating symptom. Two of the available studies examining the use of docetaxel with and without estramustine for treatment of androgen-independent prostate cancer include a detailed prospective analysis of pain and quality of life. One study required patients to have pain at entry and demonstrated significant improvement in pain. The second study enrolled patients with low prevalence and intensity of pain and did not demonstrate pain relief. The available results, although preliminary, suggest that patients with significant bone pain due to androgen-independent prostate cancer can experience substantial pain relief with docetaxel-based therapy. Larger randomized studies targeting patients with sufficient prevalence and intensity of pain are needed to refine our understanding of the contribution of docetaxel to pain control in this patient population.

ENHANCED TRANSGENE EXPRESSION IN ANDROGEN INDEPENDENT PROSTATE CANCER GENE THERAPY BY TAXANE CHEMOTHERAPEUTIC AGENTS

Chemotherapy is often used as a primary therapy for metastatic cancer because it kills cells en masse. However, high doses of chemotherapeutic drugs can cause toxicity in nontarget organs. Gene therapy may provide a better alternative to chemotherapy because its targeting of specific genes may reduce the undesirable toxicity associated with chemotherapy. We evaluated whether the chemotherapeutic agent docetaxel or paclitaxel may be combined with gene therapy to create a new therapeutic regimen for metastatic androgen independent prostate cancer. The 2 androgen independent prostate cancer cell lines PC-3 and DU 145 were treated with docetaxel or paclitaxel. Three recombinant adenoviruses containing p21WAF-1/CIP1, p53 protein or beta-galactosidase complementary DNA under the control of cytomegalovirus promoter were used to determine transgene expression. They were evaluated by Western blot analysis, beta-galactosidase activity or in vitro growth assays. The [(3)H] labeled E1 deleted adenovirus dl312 was used to determine adenovirus uptake into cells. Docetaxel and paclitaxel enhanced adenovirus mediated transgene expression. Docetaxel appears to be a more potent growth inhibitor in vitro. Elevated transgene expression in virus infected cells induced by these 2 drugs was produced by increased cytomegalovirus promoter activity rather than increased virus uptake. The potential synergy of gene therapy with docetaxel and paclitaxel may be an important direction for future therapy for metastatic androgen independent prostate cancer.

Phase II study of docetaxel and estramustine in metastatic androgen-independent prostate cancer

Phase II study of docetaxel and estramustine in metastatic androgen-independent prostate cancer

Docetaxel, estramustine, plus trastuzumab in patients with metastatic androgen-independent prostate cancer

The incidence of human epidermal growth factor receptor 2 (HER2) protein overexpression and its prognostic value are not well characterized in patients with prostate cancer. A phase I study was designed to evaluate docetaxel/estramustine plus trastuzumab, a humanized monoclonal antibody that binds to the HER2 receptor, in patients with metastatic androgen-independent prostate cancer (AIPC). HER2 positivity was not required because safety was the primary endpoint. Patients received oral estramustine 280 mg three times daily (days 1 to 5); docetaxel, 70 mg/m 2 intravenously (day 2); and trastuzumab, 2 mg/kg intravenously (days 2, 9, and 19), every 21 days until the disease progressed or toxicity became unacceptable. This regimen was well tolerated among the first 13 treated patients. Grade 4 neutropenia was seen in 10% of administered cycles. There were two episodes of febrile neutropenia and two thrombembolic events. Of the 13 patients evaluable for prostate-specific antigen (PSA) response, nine (69%) experienced a decrease in PSA level of >50%. Two (33%) of six patients with measurable disease had objective responses, and one complete response was seen on bone scan. Docetaxel/estramustine/trastuzumab appears to be a safe combination when used in the treatment of metastatic AIPC. The response data are too preliminary for speculation about the relative benefits of this 3-drug regimen compared with the combination of only docetaxel and estramustine in this clinical setting.

Docetaxel, estramustine, plus trastuzumab in patients with metastatic androgen-independent prostate cancer

Docetaxel, estramustine, plus trastuzumab in patients with metastatic androgen-independent prostate cancer

2-Methoxyestradiol Induces G2/M Arrest and Apoptosis in Prostate Cancer

Few therapeutic treatment options are available for patientssuffering from metastatic androgen-independent prostate cancer. We investigated the ability of the estrogen metabolite 2-methoxyestradiol to inhibit the proliferation of a variety of human prostate cancer cell lines in vitro and to inhibit the growth of androgen-independent prostate cancer in a transgenic mouse model in vivo. Our results showed that 2-methoxyestradiol is a powerful growth inhibitor of LNCaP, DU 145, PC-3, and ALVA-31 prostate cancer cells. Cell flow cytometry of 2-methoxyestradiol-treated DU 145 cells showed a marked accumulation of cells in the G2/M phase of the cell cycle and an increase in the sub-G1 fraction (apoptotic). In addition, staining for annexin V, changes in nuclear morphology, and inhibition of caspase activity support a role for apoptosis. More importantly, we showed that 2-methoxyestradiol inhibits prostate tumor progression in the Gγ/T-15 transgenic mouse model of androgen-independent prostate cancer without toxic side effects. These results in cell culture and an animal model support investigations into the clinical use of 2-methoxyestradiolin patients with androgen-independent prostate cancer.

A randomized phase II trial of docetaxel (taxotere) plus thalidomide in androgen-independent prostate cancer

New therapeutic alternatives are needed to improve outcomes in patients with androgen-independent prostate cancer (AIPC). For several years, researchers at the National Cancer Institute have been interested in elucidating the importance of angiogenesis in the pathogenesis of prostate cancer and in identifying inhibitors of this process. Thalidomide has been shown to inhibit the ability of tumors to recruit new blood vessels. In a recent phase II trial of thalidomide in AIPC, 28% of patients achieved a prostate-specific antigen (PSA) decrease of >40%. The taxane docetaxel also produces PSA and measurable disease responses when used as monotherapy or as a component of combination chemotherapy for AIPC. Thus, based on the single-agent activity of thalidomide and docetaxel, we initiated a randomized phase II study of weekly docetaxel with or without thalidomide, 200 mg at bedtime, in patients with chemotherapy-naive metastatic AIPC. Docetaxel, 30 mg/m 2 intravenously, was administered every 7 days for 3 weeks, followed by a 1-week rest period. Both regimens have been well tolerated among the first 59 treated patients, with a near absence of grade 3 4 myelosuppression. Fatigue, hyperglycemia, and pulmonary toxicity were seen in both groups. Thrombotic events have been seen in the combination arm. Thirty-five percent (6 of 17) of the patients receiving docetaxel alone and 53% (19 of 36) of those receiving docetaxel and thalidomide have had a PSA decrease of at least 50%. Combining a cytotoxic agent with an angiogenesis inhibitor is a promising area of investigation for prostate cancer management.

Thalidomide neuropathy in patients treated for metastatic prostate cancer

We prospectively evaluated thalidomide-induced neuropathy using electrodiagnostic studies. Sixty-seven men with metastatic androgen-independent prostate cancer in an open-label trial of oral thalidomide underwent neurologic examinations and nerve conduction studies (NCS) prior to and at 3-month intervals during treatment. NCS included recording of sensory nerve action potentials (SNAPs) from median, radial, ulnar, and sural nerves. SNAP amplitudes for each nerve were expressed as the percentage of its baseline, and the mean of the four was termed the SNAP index. A 40% decline in the SNAP index was considered clinically significant. Thalidomide was discontinued in 55 patients for lack of therapeutic response. Of 67 patients initially enrolled, 24 remained on thalidomide for 3 months, 8 remained at 6 months, and 3 remained at 9 months. Six patients developed neuropathy. Clinical symptoms and a decline in the SNAP index occurred concurrently. Older age and cumulative dose were possible contributing factors. Neuropathy may thus be a common complication of thalidomide in older patients. The SNAP index can be used to monitor peripheral neuropathy, but not for early detection.