Table 4.
Selected studies of anti-angiogenic compounds in the treatment of prostate cancer.
| Agent (Author, Year) | Phase-Population | N= | Results | Grade 3 or 4 toxicity |
|---|---|---|---|---|
| Bevacizumab (Reese, 2001) |
II mCRPC |
15 | OR: 0% (0/15) PSA: 0% (0/15) |
2 hyperglycemia, 1 anemia, 3 hyperkalemia (all thought to be unrelated) |
| Bevacizumab + Docetaxel + Estramustine (Picus, 2004) |
II mCRPC |
79 | OR: 42% (14/33) PSA: 79% |
5 VTE with 1 death mesenteric vein thrombus, 1 perforated sigmoid diverticulum, <3% febrile neutropenia |
| Bevacizumab + Docetaxel (DiLorenzo, 2008) |
II Doc-resistant mCRPC |
20 | OR: 37.5% (3/8) PSA: 55% (11/20) mPFS=4 mo, mOS=9 mo |
Grade 4: 1 neutropenia and 1 thrombocytopenia. Grade 3: 3 neutropenia, 2 nausea/vomiting, 1 neuropathy |
| Bevacizumab + Docetaxel + Thalidomide + Prednisone (Ning, 2008) |
II Chemo-naïve mCRPC |
60 | OR: 62% (20/32) PSA: 88% (51/60) mPFS=18.2 mo, mOS=26.7 mo |
febrile neutropenia (5/60), syncope (5/60), GI perforation or fistula (3/60), thrombosis (3/60), grade 3 bleeding (2/60) |
| AZD-2171 (Cediranib) (Karakunnel, 2009) |
II Doc-resistant mCRPC |
34 | OR: 17% (4/23) PSA not reported mPFS and mOS not reported |
vomiting (2), prolonged QTc interval (1) and muscle weakness (3), weight loss (3), dehydration (4), fatigue (6), hypoxia (1), renal failure (1), transaminitis (3), and anorexia (1) |
| Sorafenib (Aragon-Ching, 2009) |
II 88% Doc-resistant mCRPC |
24 | OR: 8% (1/13) PSA not reported mPFS =3.7 mo, mOS=18 mo |
Lab abnormalities (9), Dermatologic (4), Fatigue (2), Nausea (1), Anemia (1), Cath DVT (1), Infxn (1) |
| Sorafenib (Steinbild, 2007) |
II Chemo-naïve CRPC and mCRPC |
55 | OR: 0% (0/55), PSA: 3.6% (2/55) mPFS= 2 mo (8 weeks) mOS= had not been reached |
Dermatologic (5), Hypertension (3), Fatigue (2), Constipation (2) |
| Sorafenib + Docetaxel + Prednisone (Mardjuadi, 2009) |
I Chemo-naïve CRPC |
24 | OR: not reported PSA: 75% (15/20) PFS and OS not reported |
febrile neutropenia (8), uncomplicated neutropenia (5), and hand-foot syndrome (4) |
| Sunitinib + Docetaxel + Prednisone (Zurita, 2009) |
I/II Chemo-naïve mCRPC |
55 | OR: 39% (13/33) PSA: 56% (31/55) mPFS 42 weeks |
neutropenia (75%), febrile neutropenia (15%), fatigue (15%), stomatitis (7%), and anorexia (7%). 33% patients required docetaxel dose reduction. |
| Metronomic Cyclophosphamide (mCTX) (Lord, 2007) |
II Chemo-naïve CRPC and mCRPC |
58 | OR: 1.7% (1/58) PSA: 3.4% (2/58) mOS had not yet been reached |
Grade 3 lymphopenia in 33%. Required dose reduction in 5 patients. |
| mCTX + Celecoxib + Dexamethasone (Fontana, 2009) |
II 68% Doc-resistant mCRPC |
28 | OR: 20% (1/5) PSA: 32% (9/28) mPFS=3 mo, mOS=21 mo |
No grade 3 or 4 adverse events were reported. |
| Thalidomide (Figg, 2001) |
II 74% chemo naïve CRPC and mCRPC |
63 | OR: 0% (0/35) PSA: 14% (9/63) mTTF: 2.1–2.2 mo mOS 15.8 mo |
18 events >=grade 3. Suicide within 30 days of study drug discontinuation in one patient. One patient developed acute AML (hx of prolonged prior cytotoxic exposure. |
| Thalidomide + Docetaxel (Dahut, 2004) |
II Chemo naïve mCRPC |
47 | OR: 35% (7/20) PSA: 53% (25/47) mPFS: 5.9 mo, mOS: 25.9 mo |
All grade 3: neutropenia (4), anemia (2), Thromboembolism (9), fatigue (2), Hyperglycemia (7) |
| Lenalidomide + Docetaxel + Prednisone (Moss, 2007) |
I mCRPC w/<2 prior Chemo regimens |
19 | OR 38.5% (5/13) PSA: 47% (9/19) PFS and OS not reported |
Grade 3 neutropenia (3), Thromboembolism (1) |
Definitions: N=: Total patients reported on study. OR: Overall Response (partial responses +complete responses). OR is only available for those patients with measurable disease and thus may report less patients than the total study number (N=). PSA: >50% decline from baseline. mPFS: median progression free survival. mOS: is median overall survival. Doc-resistant: patients had progressed on prior docetaxel therapy. When possible, grade 3 and 4 toxicity was limited to toxicity that was thought to be drug-related. mTTF: median time to failure.