|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
© 2001 American Society for Clinical Oncology Phase II Study of Docetaxel, Estramustine, and Low-Dose Hydrocortisone in Men With Hormone-Refractory Prostate Cancer: A Final Report of CALGB 9780From the University of Massachusetts Memorial Health Care, Worcester, and Boston Medical Center, Boston, MA; Cancer and Leukemia Group B Statistical Center, Durham, and University of North Carolina, Chapel Hill, NC; University of Maryland, Baltimore, MD; University of California, San Francisco, San Francisco, CA; and University of Chicago, Chicago, IL. Address reprint requests to Diane Savarese, MD, University of Massachusetts Memorial Medical Center, University Campus, 55 Lake Ave North, Worcester, MA 01655; email: dsavarese{at}uptodate.com
PURPOSE: To investigate the combination of docetaxel, estramustine (EM), and low-dose hydrocortisone in men with hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: Combinations of EM with other antimitotic agents such as docetaxel are synergistic in vitro and show significant clinical activity in patients with HRPC. We studied intravenous administration of docetaxel 70 mg/m2, oral estramustine, and low-dose daily hydrocortisone in men with HRPC who demonstrated progression after initial hormone therapy. RESULTS: Of the 47 men enrolled onto this multicenter cooperative group study, 46 were assessable for response and/or toxicity. In the 24 patients with measurable disease, there were three complete and nine partial responses for a measurable disease response rate of 50% (12 of 24 patients; 95% confidence interval [CI], 27% to 73%). In the 44 patients in whom pretreatment prostate-specific antigen (PSA) was elevated, 30 (68%) had a 50% or greater decrease, and 25 (57%) had a 75% or greater decrease in PSA. The combined measurable disease and biochemical response rate in all 46 assessable patients was 54% (three complete responses, 22 partial responses, 95% CI, 37% to 71%). The predominant toxicity was neutropenia, with 26% of patients having grade 3 and 30% having grade 4 granulocytopenia; there were no episodes of febrile neutropenia. Other common but mild adverse effects included malaise/fatigue, peripheral edema, and hyperglycemia. The incidence of thromboembolic events during therapy was 9%. With a median follow-up of 17 months, the median survival was 20 months. The median time to disease progression was 8 months for all patients, and 10 months for those with measurable disease. CONCLUSION: This therapy is efficacious and moderately well tolerated in HRPC and should be compared in a phase III trial with mitoxantrone and prednisone.
ALTHOUGH THE VAST majority of men with metastatic prostate cancer respond initially to androgen ablation, most, if not all, will eventually develop hormone-refractory progressive disease; their median survival is generally less than 1 year from that point. An antiandrogen withdrawal response may be observed in up to 30% of patients, and a response to other secondary hormonal manipulations can be seen in up to 65% of patients.1-3 However, these responses are generally less than 6 months in duration. Systemic chemotherapy, long thought to be ineffective in hormone-refractory prostate cancer (HRPC), has been shown to improve quality of life, although overall survival has not been affected by any regimen to date.4,5 Estramustine phosphate is rapidly dephosphorylated in vivo to estramustine (EM), which dysregulates normal microtubule assembly, resulting in cell growth inhibition in human prostate cancer cell lines.6-10 Although single-agent EM has limited activity in men with HRPC,11 combinations of estramustine phosphate with other antimicrotubule agents have been studied in men with HRPC for several years. Preclinical and clinical studies indicate that the activity of EM may be synergistic with other antimitotic agents such as vinblastine, etoposide, paclitaxel, and docetaxel.12-18 Docetaxel, a semisynthetic taxoid, disrupts the cellular microtubular network, promoting assembly of stable microtubules and inhibiting disassembly approximately twice as effectively as paclitaxel.19 Further, tissue culture studies suggest that the dose required for 50% inhibition of growth by docetaxel in combination with EM is 60-fold lower than for paclitaxel plus EM.14 Two phase I trials combining docetaxel and EM have been reported.18,20 Kreis et al18 treated 17 patients with HRPC with fixed-dose EM administered 14 mg/kg/d x 21 days and escalating doses of docetaxel, ranging from 40 to 80 mg/m2 on day 1 of each treatment cycle. The maximally tolerated dose of docetaxel in this combination was 80 mg/m2, and dose limiting toxicity was leukopenia and fatigue. The recommended phase II dose was 70 mg/m2. Eighty-two percent of the treated patients had a more than 50% decrease in serum prostate-specific antigen (PSA), with 24% normalizing their PSA. One of six patients with soft tissue disease had a partial response (PR). In the second study, escalating doses of docetaxel from 40 mg/m2 to 70 mg/m2 were administered every 21 days with fixed-dose EM 280 mg orally tid.20 In contrast to the Kreis study,18 in which EM was administered every day, patients received EM for only the first 5 days of each 21-day treatment cycle. The maximally tolerated dose of docetaxel was 70 mg/m2 for minimally pretreated patients (two or fewer prior chemotherapy regimens, two or fewer prior radiotherapy courses, no Superscan appearance on radionuclide bone scan, no radioisotopes, and no prior pelvic radiation). Dose limiting toxicity was granulocytopenia, and the recommended phase II dose of docetaxel was 70 mg/m2. The docetaxel dose was not escalated above 60 mg/m2 in extensively pretreated patients (all patients other than those described as minimally pretreated); the recommended phase II dose was 60 mg/m2. A decline in serum PSA levels of 50% or greater was seen in 70% and 50% of the minimally and extensively pretreated patients, respectively, and five of 18 patients (28%) with bidimensionally measurable disease had a PR. Although the two phase I studies are not directly comparable, there seemed to be less toxicity with the 5-day schedule of EM administration. Based on encouraging preclinical data and the suggestion of efficacy with tolerable toxicity in phase I studies, the Cancer and Leukemia Group B (CALGB) conducted a phase II study of docetaxel, EM, and low-dose daily hydrocortisone in men with HRPC. Hydrocortisone was added to the docetaxel/EM combination in an effort to allow comparison with prior regimens explored within the CALGB, including mitoxantrone5 and suramin.21 Preliminary results of this study have been published previously.22
Patient Selection Patients were considered eligible for the study if they had histologically documented metastatic adenocarcinoma of the prostate with progressive systemic disease despite androgen deprivation, and no prior chemotherapy. Prior corticosteroid therapy was allowed. Patients had to have either measurable or assessable nonosseous disease, or bone involvement only with an elevated PSA (> 8 ng/mL). Measurable soft tissue disease was defined as any lesion 1 cm x 1 cm or greater in bidimensional measurements. Patients treated with an antiandrogen were required to have progressive disease despite antiandrogen withdrawal. Primary testicular androgen suppression (eg, luteinizing hormone releasing hormone analog) was continued in all patients. Patients were required to have an Eastern Cooperative Oncology Group performance status of 0 to 2, with at least 3 weeks since major surgery, at least 4 weeks since completion of radiation, and at least 8 weeks since the last dose of a therapeutic radionuclide such as strontium-89 or samarium-153. Required laboratory values included granulocytes more than 1,500/µL, platelets more than 100,000/µL, creatinine less than 1.5 times the upper limit of normal (ULN), bilirubin less than ULN, and AST less than 1.5 times the ULN. Patients with uncontrolled or severe cardiovascular disease, a history of thromboembolism within the prior 6 months, active thrombophlebitis, or clinically significant neuropathy were excluded from the trial.
Treatment and Evaluation Patients were evaluated for response radiographically or by repeat radionuclide bone scan after the first two cycles (6 weeks) and then every 3 months while on study. Weekly complete blood cell counts were required during treatment and serum PSA levels were drawn every 3 weeks (on the first day of each new cycle) during active treatment. Patients were treated until progression, complete response (CR), the development of treatment-limiting toxicity, or withdrawal of consent. A CR required complete disappearance of all evidence of all sites of disease with normalization of serum PSA (defined as a serum PSA < 4 ng/mL for patients without prior radical prostatectomy, and < 1 ng/mL for those with prior prostatectomy), on at least two occasions, at least 4 weeks apart. For patients with no measurable or assessable soft tissue disease, CR required complete normalization of bone scan and normalization of PSA on at least two occasions, at least 4 weeks apart, with a stable or improved performance status. When the protocol was initially written, the definition of PR for patients with bidimensionally measurable disease consisted of a 50% greater reduction in the sum of the products of the perpendicular diameters of all measurable masses, and a 75% or greater reduction of PSA with a stable or improved performance status. Patients with measurable disease were not classified as having a PR unless there was a soft tissue response that met those criteria. A PR in "bone-only" patients was defined as a 75% or greater decline in PSA with a stable or improved performance status in the initial protocol. The consensus criteria for assessing responses in phase II trials of cytotoxic agents for the treatment of HRPC were published23 after the study was activated. In reporting the study results, PSA declines were tabulated in accordance with the consensus guidelines, using a 50% or greater decline in PSA to constitute a PR. Time to PSA progression was also calculated according to these criteria. For patients with soft tissue measurable disease, the date of progression was defined as either (1) the date of the first computed tomography (CT) scan that demonstrated either new lesions or a 25% increase in the bidimensional measurements of previously measured disease, or (2) by an increase in the serum PSA concentration. For patients with elevated serum PSA (with either assessable or measurable disease), progressive disease was defined as three consecutive increases in PSA, at least 4 weeks apart. However, the date of disease progression was the date of the first increase in serum PSA. For those with bone disease, new lesions on radionuclide bone scan (but not worsening of the intensity of existing lesions) qualified as progressive disease. A worsened performance status by at least one level in the absence of objective disease progression also constituted progressive disease.
Statistical Design and Analyses
Patient Characteristics The pretreatment characteristics of the men entered onto this trial are listed in Table 1. Between March and December 1998, 47 men with HRPC were entered onto this multicenter trial. Forty-six of these 47 patients were eligible; one patient was entered onto the study but never treated because of continued antiandrogen therapy. Ninety-one percent of the patients were white, and the median age was 73 years (range, 67 to 77 years). Eastern Cooperative Oncology Group performance status score was 0 or 1 in 41 men (89%) and five patients had a performance status of 2. The median PSA at study entry was 166 ng/mL (interquartile range, 45 to 419 ng/mL). Bidimensionally measurable disease was present in 52% of the patients; the majority of these had lymphadenopathy. Sites of metastatic disease included bone (80%), lymph nodes (50%), lung (9%), and liver (4%). Antiandrogen therapy had previously been received by 95% of the men, 67% had previously been treated with a luteinizing hormone releasing hormone agonist, and 33% were previously castrated as the initial form of androgen ablation. Prior corticosteroid therapy had been received by 10 men (22%). Of the 30 men who had received radiation, the pelvis had been irradiated in 15 (33%).
Study Treatment All 46 eligible patients were included in the evaluation of response and toxicity. A median of five cycles of therapy was administered (range, one to 21), and eight patients received more than eight cycles of therapy. Information on the reason for discontinuing therapy was available in 39 subjects and due to progressive disease in 12, toxic effects in eight, a CR in two, patient preference (withdrawal of consent) in 11, death in three, other complications in three, and the reason was not specified in seven.
Antitumor Effects Of the 22 patients with assessable disease only, 13 patients had a PR that was based on a 50% decline in PSA (59%, 95% CI, 34% to 81%). Of the 44 patients with elevated baseline PSA who had subsequent follow-up PSA testing, 30 (68%) had a 50% or greater decrease in PSA, with 25 (57%) having 75% or greater decreases in PSA ( Table 2). The overall objective response rate, including both soft tissue measurable disease and biochemical response, was 54% (95% CI, 37% to 71%).
Survival The median follow-up time was 17 months (95% CI, 15 to 18 months). The median survival time for all patients was 20 months (95% CI, 17 to 25 months) ( Fig 1). The median time to disease progression was 10 months (95% CI, 5 to 16 months) for patients with measurable disease and 7 months (95% CI, 4 to 8 months) for patients with assessable (bone only) disease. The median time to disease progression for all patients combined was 8 months (95% CI, 5 to 10 months). As of the time of this report, 22 patients have died.
For patients with a CR or PR in measurable disease sites, progression was determined by either an increase in PSA or a worsening of soft tissue disease. Two of the three men with a CR had continued absence of measurable disease in the subsequent follow-up CT scan (performed 3 months later); one has not demonstrated disease progression for 14 months either by soft tissue or PSA criteria. The other two patients’ disease progressed by an increase in serum PSA, 3 and 6 months after attaining CR. For the 10 patients with an objective PR, the soft tissue response was either stable or continuing on the next CT in seven; one was removed from protocol for pneumonia after achieving a PR, a second patient was removed from protocol after PR was attained because of a hypertensive reaction to the docetaxel infusion, and one patient had a "slight increase" in nodal dimensions that did not meet objective criteria for progression (a 25% increase in the bidimensional products) on the next CT scan after the attainment of PR. Thus, the majority of patients with objective soft tissue measurable disease had a response that lasted beyond the next follow-up CT scan.
Adverse Effects
Dyspnea was reported by 17 of the 46 patients (37%), and was grade 3 or 4 in 10 of these patients (22%). The etiology of dyspnea was unclear; it did not seem to be directly related to pleural effusion (which only occurred in six patients) or congestive heart failure. Frequent grade 1 or 2 toxicities included peripheral edema (54% of patients), hyperglycemia (46% of patients), malaise/fatigue (34% of patients), nausea (31%) without significant vomiting, anorexia (26%), and paresthesias (22% of patients). Abnormalities in liver function tests were mild and reversible in all cases. Docetaxel dose reduction was required due to toxic effects in only six patients (transaminase elevation in two; and thrombocytopenia, diarrhea, dysphagia/mucositis, and lethargy/paresthesias, in one patient each). Docetaxel was discontinued without a dose reduction in two patients, one for a hypersensitivity reaction to docetaxel, and one for acute hypertension during the infusion. Eleven patients withdrew consent for treatment while on study. Although the reasons for treatment discontinuation were not always clear, in many cases discontinuation seemed due to low-grade symptoms (mostly fatigue and asthenia) that did not meet formal criteria for dose reduction. The median number of treatment cycles received by these 11 patients (median, four; interquartile range, three to 10) did not differ from the remainder of the study population, nor was their reported toxicity profile different.
This is the first multicenter trial demonstrating that the combination of docetaxel, EM, and low-dose hydrocortisone is an effective and tolerable regimen for men with HRPC. The response rates, both in measurable disease and in biochemical parameters, are higher than those published for other EM combination regimens containing vinblastine, etoposide, or paclitaxel.15-18 Response proportions were greater in this study than in CALGB 9182,5 a randomized comparison of mitoxantrone with or without low dose hydrocortisone, in which 50% or greater PSA declines were reported in 38% and 29% of patients in the mitoxantrone plus hydrocortisone and hydrocortisone alone groups, respectively. Our response data are consistent with several other single institution studies of docetaxel and EM. In one study of 35 patients with HRPC,24 which was reported in abstract form only, EM was administered orally at a dose of 280 mg three times daily on days 1 through 5 of each treatment cycle, with docetaxel 70 mg/m2 intravenously on day 2 of each 21-day treatment cycle, identical to the doses we report here. Coumadin and aspirin were administered to the last 15 patients enrolled onto the study. Patients received a median of eight treatment cycles (range, one to 19). Twenty-three patients (74%) had PSA decline of 50% or greater, and the median duration of the PSA response was 18 weeks. The median time to objective progression was not reported. Seven of the 35 patients had measurable soft tissue disease; four of these (57%) had a soft tissue PR, all in lymph nodes. Eleven patients required dose reductions secondary to toxicity. Two patients had cerebrovascular accident and two had deep venous thrombosis; there were two treatment-related deaths related to neutropenic sepsis. The median survival time reported by Petrylak et al24 was 22 months, which is similar to the median survival of 20 months reported here. In the second single-institution phase II study,25 also reported in abstract form only, patients received short course EM (280 mg orally every 6 hours for five doses only), docetaxel 70 mg/m2 every 21 days, plus Coumadin 2 mg orally daily. Of 32 assessable patients, 13 of 29 (45%) had a 50% or greater decline in PSA for 4 weeks or longer, and three (23%) of 13 patients had soft tissue partial responses. Eighty percent of symptomatic patients had improvement in pain or urinary symptoms. No thromboembolic complications were reported by Sinibaldi et al,25 and median survival was not reported. The median survival (20 months) was longer in our study than has been reported in most of the other phase II studies evaluating combination chemotherapy regimens in HRPC. Although the median survival in our study seems to have been prolonged by treatment, other possible causes, such as patient selection or stage migration, may have contributed to this finding. However, a comparison of these data with other contemporary series of chemotherapy treatment in men with HRPC is illustrative. As an example, in CALGB 9182, the median survival in patients treated with mitoxantrone and prednisone was 12.3 months.5 Although these studies cannot be compared using formal statistical methods, both studies were performed in the same multiple institutions within the CALGB, and these results provide support for a subsequent randomized comparison between the docetaxel EM combination and mitoxantrone plus a glucocorticoid. An intergroup phase III trial of EM/docetaxel versus mitoxantrone/prednisone by the Southwest Oncology Group, the CALGB, and the North Central Cancer Treatment Group is currently underway. This study is powered to detect a 33% difference in median survival between the two groups. To date, 165 patients have been accrued to the study (D. Petrylak, personal communication, August 22, 2000). However, significant differences in the docetaxel/EM regimen used in this study may impact on efficacy. The docetaxel dose is 60 mg/m2, as compared with 70 mg/m2 used in CALGB 9780, and continuous low dose hydrocortisone is not included in the docetaxel/EM arm. In addition, the dexamethasone dose is substantially higher, a fact that may impact significantly on the incidence and/or severity of hyperglycemia and edema. This combination regimen seems to have an acceptable safety profile. Although there are potentially overlapping gastrointestinal and vascular toxicities with the agents used, few patients developed grade 3 or 4 nausea, vomiting, or diarrhea. Mild electrolyte abnormalities were common, as has been previously reported.18 EM-based regimens have been associated with thromboembolic events. In the four HPRC trials in which EM was administered with docetaxel every 3 weeks, the incidence of this complication (approximately 10%) was similar across all of the studies ( Table 4). In a preliminary report of weekly docetaxel and EM, the incidence of thromboembolic events was also similar.26 EM is known to be thrombogenic and patients with metastatic prostate cancer may be hypercoagulable at baseline. The relative contribution of docetaxel, if any, to the incidence of thromboembolic events is unclear. Although this study did not address the use of antithrombotic prophylaxis, anticoagulation may be indicated in future trials involving this combination therapy in patients with HRPC.
It is unknown if EM is essential to this regimen’s efficacy. Two studies of single-agent docetaxel in men with HRPC have been reported,27,28 both in preliminary form. In the first study, 35 men with HRPC were treated with docetaxel 75 mg/m2 every 3 weeks, 45% had a 50% or greater PSA decline, and there was one complete and five partial responses in soft tissue disease; median survival was not reported.27 In the second report, of 20 men receiving docetaxel 75 mg/m2 every 3 weeks, 38% had a 50% or greater PSA decline, and one patient had a soft tissue response.28 Median survival was not provided in either report. Further refinements in this treatment may be possible, for example, the use of weekly docetaxel either alone or in combination with EM.29 In conclusion, docetaxel/EM/hydrocortisone is efficacious and reasonably well tolerated in patients with HRPC. These results support an enhanced role for systemic chemotherapy in the management of HRPC. An ongoing phase III trial comparing docetaxel/EM to mitoxantrone/prednisone will better define the role of docetaxel/EM-based therapy in the management of patients with HRPC.
APPENDIX
Supported in part by grant no. CA31946 from the National Cancer Institute to the Cancer and Leukemia Group B (Richard L. Schilksy, MD, Chairman) and by a grant from Aventis Pharmaceuticals (Bridgewater, NJ).
The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.
1. Scher H, Kelly WK: Flutamide withdrawal syndrome: Its impact on clinical trials in hormone-refractory prostate cancer. J Clin Oncol 11: 1566-1572, 1993
2.
Small E, Vogelzang N: Second-line hormonal therapy for advanced prostate cancer: A shifting paradigm. J Clin Oncol 15: 382-388, 1997 3. Dawson N, Conaway M, Halabi S, et al: A randomized study comparing standard versus moderately high dose megestrol acetate for patients with advanced prostate carcinoma: Cancer and Leukemia Group B study 9181. Cancer 88: 825-834, 2000[Medline]
4.
Tannock I, Osoba D, MR S, et al: Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: A Canadian randomized trial with palliative end points. J Clin Oncol 14: 1756-1764, 1996
5.
Kantoff P, Halabi S, Conaway M: Hydrocortisone with or without mitoxantrone in men with hormone refractory prostate cancer: The results of CALGB 9182. J Clin Oncol 17: 2506-2513, 1999 6. Hartley-Asp B, Gunnarson P: Growth and cell survival following treatment with estramustine, nor-nitrogen mustard, estradiol and testosterone of a human prostate cancer cell line (DU-145). J Urology 127: 818-822, 1982[Medline]
7.
Stearns ME, Wang M, Tew KT, et al: Estramustine binds a MAP-1-like protein to inhibit microtubule assembly in vitro and disrupt microtubule organization of DU-145 cells. J Cell Biol 107: 2647-2656, 1988 8. Eklov S, Nilsson S, Larson A, et al: Evidence for a non-estrogenic cytostatic effect of estramustine on human prostatic carcinoma cells in vivo. The Prostate 20: 43-50, 1992[Medline] 9. Speicher L, Liang N, Barone L, et al: Interaction of an estramustine photoaffinity analogue with cytoskeletal proteins in prostate carcinoma cells. Molecular Pharmacol 46: 8866-8872, 1994 10. Hartley-Asp B: Estramustine-induced mitotic arrest in two human prostatic carcinoma cell lines DU-145 and PC-3. The Prostate 5: 93-100, 1984[Medline] 11. Yagoda A, Smith J Jr, Soloway M, et al: Phase II study of estramustine phosphate in advanced hormone refractory prostate cancer with increasing prostate specific antigen levels. J Urol 145: 384A, 1991 (abstr)
12.
Mareel M, Storme G, Dragonetti C, et al: Antiinvasive activity of estramustine on malignant MO4 mouse cells and on DU-145 human prostate carcinoma cell lines. Cancer Res 48: 1842-1849, 1992
13.
Speicher L, Barone L, Tew K: Combined antimicrotubule activity of estramustine and Taxol in human prostatic carcinoma cell lines. Cancer Res 52: 4433-4440, 1992 14. Kreis W, Budman D, Calabro A: Unique synergism or antagonism of combinations of chemotherapeutic and hormonal agents in human prostate cancer cell lines. Br J Urol 79: 196-202, 1997[Medline] 15. Amato R, Ellerhorst J, Sella A, et al: Estramustine and vinblastine for patients with progressive androgen independent adenocarcinoma of the prostate. Urol Oncol 1: 168-172, 1995 16. Hudes G, Nathan F, Khater C, et al: Phase II trial of 96-hour paclitaxel plus estramustine phosphate in metastatic hormone-refractory prostate cancer. J Clin Oncol 15: 3156-3163, 1997[Abstract]
17.
Pienta K, Redman B, Hussain M, et al: Phase II evaluation of oral estramustine and oral etoposide in hormone-refractory adenocarcinoma of the prostate. J Clin Oncol 12: 2005-2012, 1994
18.
Kreis W, Budman D, Fetten J, et al: Phase I trial of the combination of daily estramustine phosphate and intermittent docetaxel in patients with metastatic hormone refractory prostate carcinoma. Ann Oncol 10: 33-38, 1999
19.
Ringel I, Horwitz S: Studies with RP56976 (Taxotere): A semisynthetic analogue of Taxol. J Natl Cancer Inst 83: 288-291, 1988
20.
Petrylak D, MacArthur R, O’Connor J, et al: Phase I trial of docetaxel with estramustine in androgen independent prostate cancer. J Clin Oncol 17: 958-967, 1999 21. Halabi S, Small E, Ansari R, et al: Results of CALGB 9480: A phase III trial of 3 different doses of Suramin for the treatment of hormone refractory prostate cancer (HRPC). Proc Am Soc Clin Oncol 19: 328a, 2000 (abstr 1291) 22. Savarese D, Taplin M-E, Halabi S: A phase II study of docetaxel (Taxotere), estramustine and low-dose hydrocortisone in men with hormone-refractory prostate cancer: Preliminary results of Cancer and Leukemia Group B 9780. Semin Oncol 26: 39-44, 1999[Medline]
23.
Bubley G, Carducci M, Dahut W, et al: Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: Recommendations from the Prostate-Specific Antigen Working Group. J Clin Oncol 17: 3461-3467, 1999 24. Petrylak D, Shelton G, England-Owen C: Response and preliminary survival results of a phase II study of docetaxel (D) and estramustine (E) in patients (Pts) with androgen-independent prostate cancer. Proc Am Soc Clin Oncol 19: 334a, 2000 (abstr 1312) 25. Sinibaldi V, Carducci M, Moore-Cooper S, et al: A phase II study evaluating docetaxel (D) and one day of estramustine phosphate (EMP) in patients (Pts) with hormone refractory prostate cancer (HRPC): Updated preliminary analysis. Proc Am Soc Clin Oncol 19: 346a, 2000 (abstr 1361) 26. Natale R, Zaretsky S: Phase I/II trial of estramustine and Taxotere in patients with metastatic hormone-refractory prostate cancer. Proc Am Soc Clin Oncol 18: 348a, 1999 (abstr) 27. Picus J, Schultz M: Docetaxel (Taxotere) as monotherapy in the treatment of hormone-refractory prostate cancer: Preliminary results. Semin Oncol 26: 14-18, 1999[Medline] 28. Friedland D, Cohen J, Miller R, et al: A Phase II trial of Docetaxel (Taxotere) in hormone-refractory prostate cancer: Correlation of antitumor effect to phosphorylation of Bcl-2. Semin Oncol 26: 19-23, 1999 29. Copur M, Tarantolo S, Hauke R, et al: Weekly estramustine (E), Taxotere (T) and dexamethasone (D) in patients with hormone refractory prostate cancer (HRPC). Proc Am Soc Clin Oncol 19: 347a, 2000 (abstr 1366) Submitted September 26, 2000; accepted January 22, 2001. This article has been cited by other articles:
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
TOP
ABSTRACT
INTRODUCTION
