Intermittent Chemotherapy as a Platform for Testing Novel Agents in Patients With Metastatic Castration-Resistant Prostate Cancer: A Department of Defense Prostate Cancer Clinical Trials Consortium Randomized Phase II Trial of Intermittent Docetaxel With Prednisone With or Without Maintenance GM-CSF

133 Background: Docetaxel remains the standard of care for patients (pts) with mCRPC. However, the optimal duration of chemotherapy (Ch) is not known. Providing Ch holidays is often undertaken, but is not well characterized. A randomized phase II trial was undertaken to test two ICh regimens. Methods: Pts with Ch naive mCRPC and KPS > 60% were eligible. Pts were treated with “induction” docetaxel 75 mg/m2 q3 weeks, and prednisone 5 mg po bid. After 6 cycles, responding pts (PSAWG1 criteria) stopped Ch and were randomized to observation (Obs) or to GM-CSF, 250 mcg/m2 sq daily for 14 days out of every 28 day cycle. Pts were followed with monthly PSA and imaging every 2 cycles until progressive disease (PD) by PSAWG1 criteria, at which point they resumed treatment with Ch, again for 6 cycles, followed by the same “off Ch” regimen. The primary endpoint was the time to PD while on Ch (time to Ch resistance.) Results: Of 97enrolled pts to date, 94 are evaluable (3 are still undergoing induction). 69 pts completed induction (25 did not due to PD, adverse events (AE), or MD choice), of which 27 had PD after 6 cycles. Thus, 42/94 evaluable pts (45%) were eligible for randomization. Of these, 21 pts underwent Obs and 21 received GM-CSF. To date, 23/42 (55%) pts who underwent a Ch holiday restarted Ch, all for PSA PD. 8/23 (35%) had a response to Ch re-initiation. (15 pts did not re-start Ch because of AE, other therapy being started, or patient choice, and 4 pts are still undergoing either Obs or GM-CSF.) Obs pts were “off Ch” for a median of 2 months (range 2-4), compared with 3 months (range 2-8) for GM-CSF pts. Conclusions: While feasible, only 45% of pts met criteria for ICh. 35% of pts responded to Ch re-initiation. Insufficient data exist to assess the impact of GM-CSF on time off Ch or time to Ch resistance. No significant financial relationships to disclose.

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A prospective randomized phase II trial evaluating maintenance GM-CSF in an intermittent chemotherapy (chemo) regimen for metastatic castration-resistant prostate cancer (mCRPC): A DoD prostate cancer clinical trials consortium trial.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.5_suppl.35 ◽

2012 ◽

Vol 30 (5_suppl) ◽

pp. 35-35

Author(s):

Eric Jay Small ◽

Vivian K. Weinberg ◽

Charles J. Ryan ◽

Celestia S. Higano ◽

Amy Mimi Lin ◽

...

Keyword(s):

Prostate Cancer ◽

Optimal Number ◽

Castration Resistant Prostate Cancer ◽

Time To Progression ◽

Gm Csf ◽

Castration Resistant ◽

Randomized Phase Ii ◽

Intermittent Chemotherapy ◽

Number Of Cycles ◽

The Impact

35 Background: The optimal number of cycles of docetaxel for patients (pts) with mCRPC is not known, and in practice, treatment breaks are common. The current study was designed to test the safety and efficacy of utilizing 6 cycles of standard docetaxel with chemo free intervals in patients who achieve and maintain a response to docetaxel. Methods: Pts with mCRPC, no prior chemo, and KPS > 60% were eligible. Pts were treated with “induction” docetaxel 75 mg/m2 q 3 weeks, and prednisone 5 mg po bid. PSAWG1 criteria were used to define response and progression. After 6 cycles, responding pts stopped chemo and were randomized to observation (Obs) or to GM-CSF, 250 mcg/m2 daily for 14 days out of every 28-day cycle. Pts were followed with monthly PSA and imaging every 2 cycles until progression, at which point docetaxel was reinitiated for another 6 cycles, followed by the same “off chemo” regimen. The primary endpoint was the time to progression while on chemo (time to chemo resistance). Results: 114 pts have been enrolled: 3 are undergoing induction, and 111 are therefore evaluable. Of these pts, 82 completed induction, (10 did not due to PD, 9 due to adverse events (AE), 10 due to pt or MD choice). Of 111 evaluable pts, 48 (43%) had a response to chemo and were eligible for randomization. 22 were randomized to Obs and 26 to GM-CSF. Of 48 randomized pts, 25 restarted chemo, all for PSA PD. (23 pts did not re-start chemo because of AE, other therapy being started, or pt choice; 1 pt is still on GM-CSF.) 6/25 (24%) pts experienced a response to the 2nd series of chemo, and 1/6 (17%) to the 3rd. The time to chemo re-initiation (n=25) was 3.1 mos in Obs pts and 4.2 mos in GM-CSF pts. Conclusions: 43% of patients met criteria for undergoing intermittent chemo. The response proportion to the 1st, 2nd, and 3rd series of docetaxel was 43%, 24% and 17%, respectively. GM-CSF may modestly delay the time to chemo re-initiation, but the sample size is small and insufficient to assess the impact of GM-CSF on time to chemo resistance.

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