Phase III data on early chemohormonal therapy in high-risk patients

Results of a study (the GETUG 12 trial) presented today at the ASCO 2010 Genitourinary Cancer Symposium in San Francisco suggest that the addition of docetaxel-based chemotherapy to androgen deprivation and radiation therapy may impact biochemical recurrence of prostate cancer in high risk patients with localized disease — but it will take a while before truly convincing results are available.

Fizazi et al. set out to investigate whether docetaxel-based chemotherapy could impact early outcomes in patient with high-risk localized prostate cancer (which meant that patients must meet at least one of the following criteria: clinical stage T3-T4; Gleason score ≥ 8, PSA > 20 ng/mL, or pathologic stage TxN+). All patients were given a pelvic lymph node dissection prior to further treatment.

After enrollment, patients were randomly assigned to one or other of two treatment arms in this study:

  • Arm A: Goserelin acetate 10.8 mg every 3 months for 3 years and 4 cycles of docetaxel 70 mg/m2 q3w + estramustine 10 mg/kg/d on days 1-5, with localized therapy administered at 3 months.
  • Arm B: Goserelin acetate 10.8 mg every 3 months for 3 years alone, with localized therapy administered at 3 months.

Local treatment consisted in radiotherapy (at a dose of 74 Gy) in 358 of the 413 patients enrolled (87 percent).

The results of the study reported today were as follows:

  • Between 11/02 and 12/06, 207 patients were randomized to arm A and 206 to arm B.
  • The median age of the patients was 63 years (range, 47 to 77 years).
  • 67 percent of patients were clinical stage  T3-T4.
  • 42 percent of patients were Gleason score 8 to 10.
  • 59 percent of patients had a PSA > 20 ng/ml.
  • 29 percent of patients were pN+.
  • 95 percent of patients received the planned 4 cycles of docetaxel and 91 percent received the planned 4 cycles of estramustine.
  • Toxicities of of chemotherapy in Arm A included
    • Grade 3-4 neutropenia (in 27 percent of patients) with febrile neutropenia in only 2 percent
    • Additional grade 3-4 toxicities such as diarrhea (5 percent), nausea (2 percent), hair loss (2 percent), and others at low levels.
  • There were no cases of toxicity-related death.
  • Moderate to severe hot flashes occurred less often in arm A than in arm B (2 percent vs. 22 percent).
  • After 3 months of systemic treatment, a serum PSA ≤ 0.2 ng/ml was observed in 34 percent of patients in Arm A  and in 15 percent of patients in arm B.
  • Chemotherapy did have a negative impact on patient quality of life in arm A but this effect disappeared when patients were re-assessed at 1 year.

Fizazi et al. conclude that docetaxel + estramustine can be combined safely with standard radiation and hormonal therapy in patients with high-risk localized prostate cancer, and with a promising impact on PSA response.

Having said that, we need to be clear that the “proof of the pudding” in this trial will be the numbers of patients who have biochemical recurrence, with progression to distant or (better) metastatic disease over time. It could take many years before such results are available — if that is ever possible given the rapid changes in treatment options for men with a rising PSA.

What this paper seems to show is that early chemohormonal therapy is certainly possible in high-risk patients. What it does not seem to show us is sufficient data to give a clear indication that such treatment is clinically meaningful over time.

One Response

  1. I wonder why Emcyt (estramustine phosphate) was used instead of prednisone. The survival benefit of Taxotere with prednisone was equivalent and with less side effects. It is good to see the use of combination treatments for prostate cancer Hopefully in time there will be a benefit.

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