A phase II study investigating the re-induction of endocrine sensitivity following chemotherapy in androgen-independent prostate cancer

Abstract

When chemotherapy is used in androgen-independent prostate cancer (AIPC), androgen deprivation is continued despite its failure. In this study, we investigated whether it was possible to re-induce hormone sensitivity in previously castrate patients by stopping endocrine therapy during chemotherapy. A phase II prospective study investigated the effects of reintroduction of endocrine therapy after oral chemotherapy in 56 patients with AIPC, which was given without concurrent androgen deprivation. After chemotherapy, patients were given maximum androgen blockade until failure when treatment was switched to diethylstilbestrol and dexamethasone. Patients had already received these endocrine treatments in the same sequence before chemotherapy. All patients were castrate at the start of chemotherapy. Forty-three subsequently restarted endocrine therapy after the completion of chemotherapy. The median overall survival for these 43 patients from the time of restarting endocrine therapy was 7.7 months (95% confidence interval (CI): 3.7 -10.9 months). Sixteen (37%) patients had a 50% PSA response to treatment, which was associated with improved overall survival (14.0 months vs 3.7 months P ¼ 0.003). Eight out of 12 patients who did not respond to diethylstilbestrol before chemotherapy did so post chemotherapy. Re-induction of hormone sensitivity can occur after chemotherapy in AIPC.

A Prospective Audit of Intermittent Anti-Androgen verses Pituitary Blockade Suggests a Bipolar Androgen Type Strategy May Be Safe in Untreated Prostate Cancer

“…These findings mirror similar observations in postmenopausal breast cancer treated with oestrogen therapy, as the response rate was higher in those over the age of 60 [42]. Possibly another example of a similar process is that a proportion of PC patients if given chemotherapy after stopping androgen blockade subsequently responded a second time to retreatment with androgen blockade [19]. This latter observation has been expanded by work done by the Baltimore Johns Hopkins group who have developed the concept of Bipolar androgen therapy (BAT) [43] and shown 7 responses in 14 castration-resistant patients to monthly high-dose testosterone injections given after oral etoposide chemotherapy.…”

“…Second-line endocrine treatment was mainly LHRH agonist in the iAAm group followed by Stilboestrol plus or minus Dexamethasone [14][15][16] followed by chemotherapy with CL56, a 2-week treatment with oral Chlorambucil and Lomustine repeated 8 weekly [17]. This had been shown to produce equivalent survival to Docetaxel with the added advantage that when given without continued androgen suppression, patients often responded a second time to previous endocrine treatments that they had initially failed and were considered to have progressed to hormone-refractory disease [17][18][19].…”

Leptomeningeal metastases from prostate cancer: an emerging clinical conundrum

“…There is also evidence that some men may respond to hormonal therapy after receiving chemotherapy [34][35][36].…”

Androgen resistance in prostate cancer

“…Sixteen of this group of 43 patients (37%) then went on to have a further PSA in response to either an LHRH agonist given with an anti-androgen or to a combination of diethylstilboestrol and dexamethasone. The responses were transient, but what is remarkable is that 12 out of 28 patients, who were treated with hormonal therapy following chemotherapy, went on to have another transient PSA response after progression on maximal androgen blockade (Shamash et al, 2007).…”