advanced prostate cancer: at last a role for medical oncologists

2
Editorial – referring to the article published on pp. 17–26 of this issue Advanced Prostate Cancer: At Last a Role for Medical Oncologists Luigi Dogliotti Department of Medical Oncology, University of Torino at San Luigi Hospital, 10043 Orbassano (Torino), Italy ‘‘What is more exciting? The activity of docetaxel in early prostate cancer or the successful collaboration between urologists and medical oncologists to complete a study in early prostate cancer?’’ The title and the content of this editorial paper by Michael Carducci, published in May 2005 [1], always aroused my enthusiasm and agreement. It appeared just a year after the presentation of the docetaxel data of TAX 327 and Southwest Oncology Group (SWOG) 9916 phase 3 trials, involving a large number of patients with advanced prostate cancer, at the 2004 annual meeting of the American Society of Clinical Oncol- ogy (ASCO). I think that the opinion of Dr. Carducci is true not only for early prostate cancer studies but also for every kind of prospective study with chemotherapy drugs or with targeted therapies. What is the background of the difficulties between urologists and medical oncologists in the treatment of prostate cancer and how can we root out prejudice? Until some years ago, at least in Italy, few medical oncologists were interested in patients with prostate cancer because their role was con- sidered negligible both by the urologists and the patients. This is true because their advice was often sought at the end of the patient history and the possible usefulness of chemotherapy to increase, at least in hormone-refractory patients, their quality of life or survival was based, until ASCO 2004, on very few well-conducted, randomised, prospective stu- dies, in terms of statistically significant numbers of accrued patients and clear definitions of the primary and secondary aims. This reality has been always astonishing for the oncologists accustomed to the enormous number of well-done trials in other types of frequently occur- ring cancers, such as breast or colon cancer. This opinion has been strengthened by a very recent clinical study reported by Collins and coworkers [2]. At the Centre for Reviews and Dissemination of the University of York, United Kingdom, they performed a systematic review to evaluate the clinical and cost effectiveness of docetaxel and prednisone versus other chemotherapy regimens or versus active supportive care or placebo for the treatment of metastatic hormone-refractory prostate cancer, on behalf of the National Institute for Clinical Excel- lence in the United Kingdom. From inception to April 2005, 1065 titles and abstracts were screened through 21 electronic resources: 267 records were full papers. Among these, only seven reported the results of randomised, controlled trials that met their inclusion criteria, but only one, the TAX 327 trial, docetaxel plus prednisone versus mitoxan- trone plus prednisone [3], was identified as the unique large, well-conducted, randomised, con- trolled trial that assessed the clinical effectiveness of docetaxel plus prednisone. On these grounds, it is easy to understand the strong impression that arose from the presentation of the final data of TAX 327 and SWOG 9916 to the thousands of oncologists attending the 2004 ASCO meeting in New Orleans. Even more impressive was the moment when the chairman of the session, Bruce J. Roth of the Vanderbilt-Ingram Cancer european urology 51 (2007) 4–5 available at www.sciencedirect.com journal homepage: www.europeanurology.com DOI of original article: 10.1016/j.eururo.2006.08.013 E-mail address: [email protected]. 0302-2838/$ – see back matter # 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2006.09.001

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e u r o p e a n u r o l o g y 5 1 ( 2 0 0 7 ) 4 – 5

avai lable at www.sc iencedi rect .com

journal homepage: www.europeanurology.com

Editorial – referring to the article published on pp. 17–26 of this issue

Advanced Prostate Cancer: At Last a Role for MedicalOncologists

Luigi Dogliotti

Department of Medical Oncology, University of Torino at San Luigi Hospital, 10043 Orbassano (Torino), Italy

‘‘What is more exciting? The activity of docetaxel in earlyprostate cancer or the successful collaboration betweenurologists and medical oncologists to complete a study inearly prostate cancer?’’ The title and the content of thiseditorial paper by Michael Carducci, published inMay 2005 [1], always aroused my enthusiasm andagreement. It appeared just a year after thepresentation of the docetaxel data of TAX 327 andSouthwest Oncology Group (SWOG) 9916 phase 3trials, involving a large number of patients withadvanced prostate cancer, at the 2004 annualmeeting of the American Society of Clinical Oncol-ogy (ASCO). I think that the opinion of Dr. Carducci istrue not only for early prostate cancer studies butalso for every kind of prospective study withchemotherapy drugs or with targeted therapies.

What is the background of the difficultiesbetween urologists and medical oncologists in thetreatment of prostate cancer and how can we rootout prejudice? Until some years ago, at least in Italy,few medical oncologists were interested in patientswith prostate cancer because their role was con-sidered negligible both by the urologists and thepatients. This is true because their advice was oftensought at the end of the patient history and thepossible usefulness of chemotherapy to increase, atleast in hormone-refractory patients, their quality oflife or survival was based, until ASCO 2004, on veryfew well-conducted, randomised, prospective stu-dies, in terms of statistically significant numbers ofaccrued patients and clear definitions of the primaryand secondary aims.

DOI of original article: 10.1016/j.eururo.2006.08.013E-mail address: [email protected].

0302-2838/$ – see back matter # 2006 European Association of Urology. Publis

This reality has been always astonishing for theoncologists accustomed to the enormous number ofwell-done trials in other types of frequently occur-ring cancers, such as breast or colon cancer. Thisopinion has been strengthened by a very recentclinical study reported by Collins and coworkers [2].At the Centre for Reviews and Dissemination of theUniversity of York, United Kingdom, they performeda systematic review to evaluate the clinical and costeffectiveness of docetaxel and prednisone versusother chemotherapy regimens or versus activesupportive care or placebo for the treatment ofmetastatic hormone-refractory prostate cancer, onbehalf of the National Institute for Clinical Excel-lence in the United Kingdom. From inception toApril 2005, 1065 titles and abstracts were screenedthrough 21 electronic resources: 267 records werefull papers. Among these, only seven reported theresults of randomised, controlled trials that mettheir inclusion criteria, but only one, the TAX 327trial, docetaxel plus prednisone versus mitoxan-trone plus prednisone [3], was identified as theunique large, well-conducted, randomised, con-trolled trial that assessed the clinical effectivenessof docetaxel plus prednisone.

On these grounds, it is easy to understand thestrong impression that arose from the presentationof the final data of TAX 327 and SWOG 9916 to thethousands of oncologists attending the 2004 ASCOmeeting in New Orleans. Even more impressive wasthe moment when the chairman of the session,Bruce J. Roth of the Vanderbilt-Ingram Cancer

hed by Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2006.09.001

e u r o p e a n u r o l o g y 5 1 ( 2 0 0 7 ) 4 – 5 5

Center, discussing the data under the title ‘‘Survivalbenefit of chemotherapy in advanced prostatecancer’’ showed what were the predictions, in theearly 2000s, of the results of the two trials:

� D

ocetaxel-based regimens would demonstrate asignificantly higher response rate.

� N

o difference would be observed with weeklyversus every 3 wk docetaxel regimens.

� T

he addition of estramustine to docetaxel wouldshow obvious benefits.

� D

ocetaxel-based regimens would be significantlymore toxic and result in inferior quality of lifecompared to mitoxantrone.

� D

ocetaxel-based regimens would not show anysurvival advantage.

It is unbelievable, but all these expectations werewrong! In particular, the modest but statisticallysignificant survival advantage with docetaxel versusmitoxantrone linked with a significant improve-ment in the quality of life was really a new event formen with hormone-refractory prostate cancer. Therapid approval by the Food and Drug Administrationin the United States and EMEA in Europe madedocetaxel every 3 weeks plus prednisone thestandard tolerable treatment in these patients.The ‘‘standard’’ treatment does not mean the ‘‘goldstandard’’ treatment! We are far from the gold mine,but the number of ongoing or designed studies, withthe cooperation of urologists and medical oncolo-gists, through the creation of ‘‘prostate cancerunits,’’ bodes well for a rapid increase in positiveresults in every step of the natural history ofprostate cancer.

The present paper on the current indications forchemotherapy in prostate cancer patients byCalabro and Sternberg is an excellent review onthe up-to-date state of the art of this important topic[4]. Presentation and discussion of ongoing studiesin the early stages of high-risk prostate cancerpatients, which could clarify new problems con-cerning the optimal timing to introduce activechemotherapy drugs and possible active targettherapies, is noteworthy. Moreover, as a medicaloncologist who follows patients with hormone-refractory prostate cancer, I wish to stress theforthcoming data on second-line chemotherapyregimens, particularly those that will emergefrom the SPARC trial. Now patients who obtained

clinical benefit from the well-tolerated docetaxeltreatment and who usually after 6 months relapsed,ask insistently to have an available second-linetreatment.

In the future, it will be important to consider thepossible usefulness of combining hormone therapywith the continuous administration of very lowdoses of chemotherapy (the so-called metronomictherapy), in the light of the recent interesting resultsobtained in patients with breast cancer [5].

The last 2 yr have changed part of the naturalhistory of advanced prostate cancer and introduceda new era. My statement is easy to understand whenyou consider what Cora Sternberg wrote today andwhat she wrote in a review on what is new in thetreatment of advanced prostate cancer, publishedexactly 3 yr ago [6]:

� N

o standard chemotherapy regimen has beendefined.

� N

o single agent or combination had improvedsurvival in randomised trials.

� C

omplete remissions were rare. � M edical oncologists were reluctant to use che-

motherapy in prostate cancer.

References

[1] Carducci MA. What is more exciting? The activity of

docetaxel in early prostate cancer or the successful col-

laboration between urologists and medical oncologists to

complete a study in early prostate cancer? J Clin Oncol

2005;15:3304–7.

[2] Collins R, Trowman R, Norman G, et al. A systematic review

of the effectiveness of docetaxel and mitoxantrone for the

treatment of metastatic hormone-refractory prostate

cancer. Br J Cancer 2006;95:457–62.

[3] Tannock IF, de Wit R, Berry WR, et al. Docetaxel

plus prednisone or mitoxantrone plus prednisone for

advanced refractory prostate cancer. N Engl J Med 2004;

351:1232–7.

[4] Calabro F, Sternberg CN. Current indications for che-

motherapy in prostate cancer patients. Eur Urol 2007;51:

17–26.

[5] Bottini A, Generali D, Brizzi MP, et al. Randomized phase II

trial of letrozole and letrozole plus low dose metronomic

oral cyclophosphamide as primary systemic treatment in

elderly breast cancer patients. J Clin Oncol 2006;24:3623–8.

[6] Sternberg CN. What’s new in the treatment of advanced

prostate cancer? Eur J Cancer 2003;39:136–46.