Generated Narrative: Citation 179631 version: 21; Last updated: 2025-10-13 12:34:35+0000 Profile: JournalArticleCitation ArtifactPublicationStatus: Active url: Citation 19029421 Phase III trial of androgen ablation with or without three cycles of systemic chemotherapy for advanced prostate cancer. identifier: FEvIR Object Identifier/179631, https://pubmed.ncbi.nlm.nih.gov/19029421, <a href="http://terminology.hl7.org/7.0.1/NamingSystem-uri.html" title="As defined by RFC 3986 (http://www.ietf.org/rfc/rfc3986.txt)(with many schemes defined in many RFCs). For OIDs and UUIDs, use the URN form (urn:oid:(note: lowercase) and urn:uuid:). See http://www.ietf.org/rfc/rfc3001.txt and http://www.ietf.org/rfc/rfc4122.txt #xD;#xA;#xD;#xA;This oid is used as an identifier II.root to indicate the the extension is an absolute URI (technically, an IRI). Typically, this is used for OIDs and GUIDs. Note that when this OID is used with OIDs and GUIDs, the II.extension should start with urn:oid or urn:uuid: #xD;#xA;#xD;#xA;Note that this OID is created to aid with interconversion between CDA and FHIR - FHIR uses urn:ietf:rfc:3986 as equivalent to this OID. URIs as identifiers appear more commonly in FHIR.#xD;#xA;#xD;#xA;This OID may also be used in CD.codeSystem.">Uniform Resource Identifier (URI)/urn:oid:2.16.840.1.113883.4.642.40.44.15.44 version: 1.0.0-ballot3 title: 19029421 Phase III trial of androgen ablation with or without three cycles of systemic chemotherapy for advanced prostate cancer. status: Active date: 2026-01-13 11:03:07+0000 author: Computable Publishing®: MEDLINE-to-FEvIR Converter: publisher: HL7 International / Clinical Decision Support contact: HL7 International / Clinical Decision Support: http://www.hl7.org/Special/committees/dss description: This Citation Resource is referenced in an example for the EBMonFHIR Implementation Guide. UseContexts - Code Value[x] * Citation Classification Type: fevir-platform-use (FEvIR Platform Use) Medline Base jurisdiction: World copyright: https://creativecommons.org/licenses/by-nc-sa/4.0/ approvalDate: 2009-01-13 lastReviewDate: 2023-02-02 classification type: Citation Source classifier: MEDLINE classification type: MEDLINE Citation Owner classifier: National Library of Medicine, Index Section currentState: Medline Citation Status of Medline, PubMed PublicationStatus of ppublish statusDate activity: PubMed Pubstatus of Pubmed period: ?? --> 2008-11-26 09:00:00+0000 statusDate activity: PubMed Pubstatus of Medline period: ?? --> 2009-01-14 09:00:00+0000 statusDate activity: PubMed Pubstatus of Entrez period: ?? --> 2008-11-26 09:00:00+0000 statusDate activity: PubMed Pubstatus of PMC release period: ?? --> 2009-12-20 citedArtifact identifier: https://pubmed.ncbi.nlm.nih.gov/19029421, https://www.ncbi.nlm.nih.gov/pmc//PMC3864402, https://doi.org/10.1200/JCO.2007.15.9830, pii/JCO.2007.15.9830 Titles - Type Text * Primary title Phase III trial of androgen ablation with or without three cycles of systemic chemotherapy for advanced prostate cancer. Abstracts - Type Text * Primary human use PURPOSE: We conducted a phase III trial in patients with previously untreated metastatic prostate cancer to test the hypothesis that three 8-week cycles of ketoconazole and doxorubicin alternating with vinblastine and estramustine, given in addition to standard androgen deprivation, would delay the appearance of castrate-resistant disease. PATIENTS AND METHODS: Eligible patients had metastatic prostate cancer threatening enough to justify sustained androgen ablation and were fit enough for chemotherapy. The primary end point was time to castrate-resistant progression as shown by increasing prostate-specific antigen, new radiographic lesions, worsening cancer-related symptoms, or receipt of any other systemic therapy. RESULTS: Three hundred six patients were registered; 286 are reported. Median time to progression was 24 months (95% CI, 18 to 39 months) in the standard therapy arm, and 35 months (95% CI, 26 to 44 months) in the chemohormonal group (P = .39). At median follow-up of 6.4 years, overall survival was 5.4 years (95% CI, 4.7 to 7.8 years) in the standard therapy arm versus 6.1 years (95% CI, 5.1 to 10.1 years; P = .41). Prostate-specific antigen kinetics at the time of androgen ablation and the nadir after hormone treatment were strongly correlated with survival. Chemotherapy significantly increased the burden of therapy, with 51% of patients experiencing an adverse event of grade 3 or worse, especially thromboembolic events. CONCLUSION: There is no role for ketoconazole and doxorubicin alternating with vinblastine and estramustine before emergence of a castrate-resistant phenotype. relatesTo type: Cites classifier: Journal Article citation: Jemal A, Siegel R, Ward E, et al: Cancer Statistics, 2007. CA Cancer J Clin 57:43-66, 2007 relatesTo type: Cites classifier: Journal Article citation: Yagoda A, Petrylak D: Cytotoxic chemotherapy for advanced hormone-resistant prostate cancer. Cancer 71:1098-1109, 1993 relatesTo type: Cites classifier: Journal Article citation: Beer T, Raghavan D: Chemotherapy for hormone-refractory prostate cancer: Beauty is in the eye of the beholder. Prostate 45:184-193, 2000 relatesTo type: Cites classifier: Journal Article citation: Ellerhorst JA, Tu SM, Amato RJ, et al: Phase II trial of alternating weekly chemohormonal therapy for patients with androgen-independent prostate cancer. Clin Cancer Res 3:2371-2376, 1997 relatesTo type: Cites classifier: Journal Article citation: Smith DC, Esper P, Strawderman M, et al: Phase II trial of oral estramustine, oral etoposide, and intravenous paclitaxel in hormone-refractory prostate cancer. J Clin Oncol 17:1664-1671, 1999 relatesTo type: Cites classifier: Journal Article citation: Kelly WK, Curley T, Slovin S, et al: Paclitaxel, estramustine phosphate, and carboplatin in patients with advanced prostate cancer. J Clin Oncol 19:44-53, 2001 relatesTo type: Cites classifier: Journal Article citation: Millikan RE, Thall PF, Lee SJ, et al: Randomized multicenter phase II trial of two multicomponent regimens in androgen independent prostate cancer. J Clin Oncol 21:878-883, 2003 relatesTo type: Cites classifier: Journal Article citation: Petrylak DP, Tangen CM, Hussain MH, et al: Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 351:1513-1520, 2004 relatesTo type: Cites classifier: Journal Article citation: Tannock IF, de Wit R, Berry WR, et al: Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351:1502-1512, 2004 relatesTo type: Cites classifier: Journal Article citation: Murphy GP, Beckley S, Brady MF, et al: Treatment of newly diagnosed metastatic prostate cancer patients with chemotherapy agents in combination with hormones versus hormones alone. Cancer 51:1264-1272, 1983 relatesTo type: Cites classifier: Journal Article citation: Murphy GP, Huben RP, Priore R: Results of another trial of chemotherapy with and without hormones in patients with newly diagnosed metastatic prostate cancer. Urology 28:36-40, 1986 relatesTo type: Cites classifier: Journal Article citation: Osborne CK, Blumenstein B, Crawford ED, et al: Combined versus sequential chemo-endocrine therapy in advanced prostate cancer: Final results of a randomized Southwest Oncology Group study. J Clin Oncol 8:1675-1682, 1990 relatesTo type: Cites classifier: Journal Article citation: Pummer K, Lehnert M, Stettner H, et al: Randomized comparison of total androgen blockade alone versus combined with weekly epirubicin in advanced prostate cancer. Eur Urol 32:81-85, 1997. (suppl) relatesTo type: Cites classifier: Journal Article citation: Janknegt RA, Boon TA, van de Beek C, et al: Combined hormono/chemotherapy as primary treatment for metastatic prostate cancer: A randomized, multicenter study of orchiectomy alone versus orchiectomy plus estramustine phosphate. Urology 49:411-420, 1997 relatesTo type: Cites classifier: Journal Article citation: Fontana D, Bertetto O, Fasolis G, et al: Randomized comparison of goserelin acetate versus mitomycin C plus goserelin acetate in previously untreated prostate cancer patients with bone metastases. Tumori 84:39-44, 1998 relatesTo type: Cites classifier: Journal Article citation: Boel K, Van Poppel H, Goethuys H, et al: Mitomycin C for metastatic prostate cancer: Final analysis of a randomized trial. Anticancer Res 19:2157-2161, 1999 relatesTo type: Cites classifier: Journal Article citation: de Reijke TM, Keuppens FI, Whelan P, et al: Orchiectomy and orchiectomy plus mitomycin C for metastatic prostate cancer in patients with poor prognosis: The final results of a European organization for research in cancer therapy genitourinary group trial. J Urol 162:1658-1664, 1999 relatesTo type: Cites classifier: Journal Article citation: Kuriyama M, Takanhashi Y, Sahashi M, et al: Prospective and randomized comparison of combined androgen blockade versus combination with oral UFT as an initial treatment for prostate cancer. Jpn J Clin Oncol 31:18-24, 2001 relatesTo type: Cites classifier: Journal Article citation: Noguchi M, Noda Shinshi, Yoshida M, et al: Chemohormonal therapy as primary treatment for metastatic prostate cancer: A randomized study of estramustine phosphate plus luteinizing hormone-releasing hormone agonist versus flutamide plus luteinizing hormone-releasing hormone agonist. Int J Urol 11:103-109, 2004 relatesTo type: Cites citation: Fisher LD, Belle GV: Biostatistics: A Methodology For the Health Sciences. New York, NY, John Wiley, 1993 relatesTo type: Cites citation: Randles RH, Wolfe DA: Introduction to the Theory of Nonparametric Statistics. New York, NY, John Wiley, 1979 relatesTo type: Cites citation: Lawless JF: Statistical Models and Methods for Lifetime Data. New York, NY, John Wiley, 1982 relatesTo type: Cites classifier: Journal Article citation: Hussain M, Tangen CM, Higano C, et al: Absolute prostate-specific antigen value after androgen deprivation is a strong independent predictor of survival in new metastatic prostate cancer: Data from the Southwest Oncology Group trial 9346 (INT-0162). J Clin Oncol 24:3984-3990, 2006 relatesTo type: Cites classifier: Journal Article citation: Stewart AJ, Scher HI, Chen M-H, et al: Prostate-specific antigen nadir and cancer-specific mortality following hormonal therapy for prostate-specific antigen failure. J Clin Oncol 23:6556-6560, 2005 relatesTo type: Cites classifier: Journal Article citation: Pettaway CA, Pisters LL, Troncoso P, et al: Neoadjuvant chemotherapy and hormonal therapy followed by radical prostatectomy: Feasibility and preliminary results. J Clin Oncol 18:1050-1057, 2000 relatesTo type: Cites classifier: Journal Article citation: Friedman J, Dunn RL, Wood D, et al: Neoadjuvant docetaxel and capecitabine in patients with high risk prostate cancer. J Urol 179:911-916, 2008 publicationForm publishedIn type: Periodical identifier: Electronic ISSN Type/1527-7755, ISOAbbreviation/J Clin Oncol, ISSN Linking/0732-183X, Medline Title Abbreviation/J Clin Oncol, NLM Unique ID/8309333 title: Journal of clinical oncology : official journal of the American Society of Clinical Oncology publisherLocation: United States citedMedium: Internet volume: 26 issue: 36 articleDate: 2008-12-20 pageString: 5936-42 publicationForm citedMedium: Internet without issue articleDate: 2008-11-24 webLocation classifier: Abstract url: https://pubmed.ncbi.nlm.nih.gov/19029421/ webLocation classifier: DOI Based url: https://doi.org/10.1200/JCO.2007.15.9830 classification type: Publishing Model classifier: Print Electronic classification type: Chemical classifier: Androgen Antagonists, Antibiotics, Antineoplastic, Antineoplastic Agents, Alkylating, Antineoplastic Agents, Phytogenic, Estramustine, Vinblastine, Doxorubicin, Ketoconazole classification type: MeSH heading artifactAssessment: ArtifactAssessment: artifact[x] = this resource classification type: Publication type classifier: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial classification type: Knowledge Artifact Type classifier: Journal Article artifactAssessment: Classifier added by Computable Publishing LLC classification type: Citation subset classifier: IM contributorship complete: true entry contributor: Millikan RE forenameInitials: RE affiliation: Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, 1155 Pressler, CPB7.3462, Houston, TX 77030, USA. rmillika@mdanderson.org entry contributor: Wen S forenameInitials: S entry contributor: Pagliaro LC forenameInitials: LC entry contributor: Brown MA forenameInitials: MA entry contributor: Moomey B forenameInitials: B entry contributor: Do KA forenameInitials: KA entry contributor: Logothetis CJ forenameInitials: CJ Generated Narrative: Practitioner #contributor0 name: Randall E Millikan Generated Narrative: Practitioner #contributor1 name: Sijin Wen Generated Narrative: Practitioner #contributor2 name: Lance C Pagliaro Generated Narrative: Practitioner #contributor3 name: Melissa A Brown Generated Narrative: Practitioner #contributor4 name: Brenda Moomey Generated Narrative: Practitioner #contributor5 name: Kim-Anh Do Generated Narrative: Practitioner #contributor6 name: Christopher J Logothetis Generated Narrative: ArtifactAssessment #meshHeading0 artifact: Citation 19029421 Phase III trial of androgen ablation with or without three cycles of systemic chemotherapy for advanced prostate cancer. content type: components (if present) include qualifier codings classifier: Adult freeToShare: true Components - 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Antineoplastic Combined Chemotherapy Protocols
19029421 Phase III trial of androgen ablation with or without three cycles of systemic chemotherapy for advanced prostate cancer.
Computable Publishing®: MEDLINE-to-FEvIR Converter
HL7 International / Clinical Decision Support
This Citation Resource is referenced in an example for the EBMonFHIR Implementation Guide.
National Library of Medicine, Index Section
Phase III trial of androgen ablation with or without three cycles of systemic chemotherapy for advanced prostate cancer.
**PURPOSE:** We conducted a phase III trial in patients with previously untreated metastatic prostate cancer to test the hypothesis that three 8-week cycles of ketoconazole and doxorubicin alternating with vinblastine and estramustine, given in addition to standard androgen deprivation, would delay the appearance of castrate-resistant disease. **PATIENTS AND METHODS:** Eligible patients had metastatic prostate cancer threatening enough to justify sustained androgen ablation and were fit enough for chemotherapy. The primary end point was time to castrate-resistant progression as shown by increasing prostate-specific antigen, new radiographic lesions, worsening cancer-related symptoms, or receipt of any other systemic therapy. **RESULTS:** Three hundred six patients were registered; 286 are reported. Median time to progression was 24 months (95% CI, 18 to 39 months) in the standard therapy arm, and 35 months (95% CI, 26 to 44 months) in the chemohormonal group (P = .39). At median follow-up of 6.4 years, overall survival was 5.4 years (95% CI, 4.7 to 7.8 years) in the standard therapy arm versus 6.1 years (95% CI, 5.1 to 10.1 years; P = .41). Prostate-specific antigen kinetics at the time of androgen ablation and the nadir after hormone treatment were strongly correlated with survival. Chemotherapy significantly increased the burden of therapy, with 51% of patients experiencing an adverse event of grade 3 or worse, especially thromboembolic events. **CONCLUSION:** There is no role for ketoconazole and doxorubicin alternating with vinblastine and estramustine before emergence of a castrate-resistant phenotype.
Jemal A, Siegel R, Ward E, et al: Cancer Statistics, 2007. CA Cancer J Clin 57:43-66, 2007
Yagoda A, Petrylak D: Cytotoxic chemotherapy for advanced hormone-resistant prostate cancer. Cancer 71:1098-1109, 1993
Beer T, Raghavan D: Chemotherapy for hormone-refractory prostate cancer: Beauty is in the eye of the beholder. Prostate 45:184-193, 2000
Ellerhorst JA, Tu SM, Amato RJ, et al: Phase II trial of alternating weekly chemohormonal therapy for patients with androgen-independent prostate cancer. Clin Cancer Res 3:2371-2376, 1997
Smith DC, Esper P, Strawderman M, et al: Phase II trial of oral estramustine, oral etoposide, and intravenous paclitaxel in hormone-refractory prostate cancer. J Clin Oncol 17:1664-1671, 1999
Kelly WK, Curley T, Slovin S, et al: Paclitaxel, estramustine phosphate, and carboplatin in patients with advanced prostate cancer. J Clin Oncol 19:44-53, 2001
Millikan RE, Thall PF, Lee SJ, et al: Randomized multicenter phase II trial of two multicomponent regimens in androgen independent prostate cancer. J Clin Oncol 21:878-883, 2003
Petrylak DP, Tangen CM, Hussain MH, et al: Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 351:1513-1520, 2004
Tannock IF, de Wit R, Berry WR, et al: Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351:1502-1512, 2004
Murphy GP, Beckley S, Brady MF, et al: Treatment of newly diagnosed metastatic prostate cancer patients with chemotherapy agents in combination with hormones versus hormones alone. Cancer 51:1264-1272, 1983
Murphy GP, Huben RP, Priore R: Results of another trial of chemotherapy with and without hormones in patients with newly diagnosed metastatic prostate cancer. Urology 28:36-40, 1986
Osborne CK, Blumenstein B, Crawford ED, et al: Combined versus sequential chemo-endocrine therapy in advanced prostate cancer: Final results of a randomized Southwest Oncology Group study. J Clin Oncol 8:1675-1682, 1990
Pummer K, Lehnert M, Stettner H, et al: Randomized comparison of total androgen blockade alone versus combined with weekly epirubicin in advanced prostate cancer. Eur Urol 32:81-85, 1997. (suppl)
Janknegt RA, Boon TA, van de Beek C, et al: Combined hormono/chemotherapy as primary treatment for metastatic prostate cancer: A randomized, multicenter study of orchiectomy alone versus orchiectomy plus estramustine phosphate. Urology 49:411-420, 1997
Fontana D, Bertetto O, Fasolis G, et al: Randomized comparison of goserelin acetate versus mitomycin C plus goserelin acetate in previously untreated prostate cancer patients with bone metastases. Tumori 84:39-44, 1998
Boel K, Van Poppel H, Goethuys H, et al: Mitomycin C for metastatic prostate cancer: Final analysis of a randomized trial. Anticancer Res 19:2157-2161, 1999
de Reijke TM, Keuppens FI, Whelan P, et al: Orchiectomy and orchiectomy plus mitomycin C for metastatic prostate cancer in patients with poor prognosis: The final results of a European organization for research in cancer therapy genitourinary group trial. J Urol 162:1658-1664, 1999
Kuriyama M, Takanhashi Y, Sahashi M, et al: Prospective and randomized comparison of combined androgen blockade versus combination with oral UFT as an initial treatment for prostate cancer. Jpn J Clin Oncol 31:18-24, 2001
Noguchi M, Noda Shinshi, Yoshida M, et al: Chemohormonal therapy as primary treatment for metastatic prostate cancer: A randomized study of estramustine phosphate plus luteinizing hormone-releasing hormone agonist versus flutamide plus luteinizing hormone-releasing hormone agonist. Int J Urol 11:103-109, 2004
Fisher LD, Belle GV: Biostatistics: A Methodology For the Health Sciences. New York, NY, John Wiley, 1993
Randles RH, Wolfe DA: Introduction to the Theory of Nonparametric Statistics. New York, NY, John Wiley, 1979
Lawless JF: Statistical Models and Methods for Lifetime Data. New York, NY, John Wiley, 1982
Hussain M, Tangen CM, Higano C, et al: Absolute prostate-specific antigen value after androgen deprivation is a strong independent predictor of survival in new metastatic prostate cancer: Data from the Southwest Oncology Group trial 9346 (INT-0162). J Clin Oncol 24:3984-3990, 2006
Stewart AJ, Scher HI, Chen M-H, et al: Prostate-specific antigen nadir and cancer-specific mortality following hormonal therapy for prostate-specific antigen failure. J Clin Oncol 23:6556-6560, 2005
Pettaway CA, Pisters LL, Troncoso P, et al: Neoadjuvant chemotherapy and hormonal therapy followed by radical prostatectomy: Feasibility and preliminary results. J Clin Oncol 18:1050-1057, 2000
Friedman J, Dunn RL, Wood D, et al: Neoadjuvant docetaxel and capecitabine in patients with high risk prostate cancer. J Urol 179:911-916, 2008
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Classifier added by Computable Publishing LLC
Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, 1155 Pressler, CPB7.3462, Houston, TX 77030, USA. rmillika@mdanderson.org