You’ve been looking at metastatic prostate cancer but this is patients who haven’t had androgen deprivation therapy yet and your patients you wanted to see whether a different therapy in addition to that worked. Tell me what it is you were trying to do, what were you trying to do here?

We’re trying to find if docetaxel at the time of androgen deprivation administration starting could increase survival over androgen deprivation therapy alone in hormone sensitive metastatic prostate cancer.

Now the reason you were trying docetaxel at this early stage was what?

Because docetaxel has demonstrated survival improvement in castration resistant prostate cancer and the aim was to demonstrate if docetaxel earlier, with a lower volume disease, less clonal resistance disease, could improve survival with androgen deprivation therapy.

Could you describe the study to me?

Yes, of course. We began the study in 2004 until 2008 and we included 385 patients. Patients were randomised between androgen deprivation therapy alone and androgen deprivation therapy with docetaxel, 75mg/m2 each 21 days up to nine cycles. Premedication was required but daily prednisone was not. Patients were randomised, the randomisation was centralised and randomisation was stratified according to systemic treatment prior received by patients and according the group that was prognostic factors.

Now you had nearly 400 patients, what happened?

What happened – the first time we looked at the primary endpoint was overall survival and secondary endpoints were biological progression free survival, clinical progression free survival, quality of life and toxicity. After a median follow-up of 50 months the first time we published the results in Lancet Oncology. The overall survival was not different between the two arms. Biological progression free survival and clinical progression free survival were improved in the docetaxel arm over the androgen deprivation arm alone. We didn’t demonstrate survival improvement. Today we have presented a longer follow-up, an updated survival analysis, with 82.9 months of follow-up. We look also at the volume disease. Dr Sweeney last year at the ASCO meeting presented the CHAARTED study in which the same hypothesis was proposed, whether docetaxel could improve survival with androgen deprivation therapy arm in hormone sensitive metastatic prostate cancer. They included 790 patients and after a median follow-up of 29 months they demonstrated that survival was improved in the docetaxel arm with 17 months improvement of survival in the docetaxel arm, with 32 months for the androgen deprivation therapy alone arm to 49 in androgen deprivation therapy and docetaxel arm.

And in your study what did you find?

Based on this result we looked at the volume disease in our patients retrospectively. We recorded all volume disease of all of our patients and we found that for the low volume disease we did not demonstrate a survival improvement and for high volume disease probably our study is under-powered. We have a non-significant 4 month trend for better overall survival but we have less high volume disease.

How do you explain the discrepancy between your results and the other study?

We have a lot of low volume disease probably. Our patients were not selected for inclusion for enrolment, it was all patients, and for the CHAARTED study at the inception only patients with high volume disease were enrolled. It’s the first response of your question. The second is in our androgen deprivation therapy arm alone 80% of our patients received docetaxel at the time of castration resistance, at the time of PSA progression and maybe they received docetaxel earlier. The hypothesis is maybe that docetaxel earlier but at the time of castration could also have an improvement in survival.

Now where is this going? I want to distill out of it a clinical message because it seems you can give some guidelines.

The message is probably in high volume disease chemotherapy would improve survival with the androgen deprivation therapy alone arm. In low volume disease we did not demonstrate this improvement and CHAARTED did not too. We are waiting for the results of the STAMPEDE study, maybe at ASCO this year, and we hope to work all together, the three studies, to give the good treatment for the good patients.

So what should doctors remember from your findings so far?

My finding is for high volume disease you need to propose to your patient docetaxel with androgen deprivation therapy. For low volume disease you have to propose androgen deprivation therapy alone but you have to make good surveillance of your patients and if PSA increases you have to propose docetaxel.