12.2.1 evaluation of target lesions
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48. Dawson, N., et al., Phase II study of suramin plus aminoglutethimide in two cohorts of patients with androgen-independent prostate cancer: simultaneous antiandrogen withdrawal and prior antiandrogen withdrawal. Clin Cancer Res, 1998. 4(1): p. 37-44.  
49. Small, E.J., A. Baron, and R. Bok, *Simultaneous antiandrogen withdrawal and treatment with* ketoconazole and hydrocortisone in patients with advanced prostate carcinoma. Cancer, 1997.  
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50. Millikan, R., et al., Randomized phase 2 trial of ketoconazole and ketoconazole/doxorubicin in androgen independent prostate cancer. Urologic oncology, 2001. 6(3): p. 111-115.  
51. Small, E.J., et al., *Ketoconazole retains activity in advanced prostate cancer patients with* progression despite flutamide withdrawal. J Urol, 1997. 157(4): p. 1204-7.  
52. Small, E.J., et al., *Antiandrogen withdrawal alone or in combination with ketoconazole in* androgen-independent prostate cancer patients: a phase III trial (CALGB 9583). J Clin Oncol, 2004. 22(6): p. 1025-33.  
53. Itakura, H., et al., *Rhabdomyolysis from cytochrome p-450 interaction of ketoconazole and* simvastatin in prostate cancer. J Urol, 2003. 169(2): p. 613.  
54. Tannock, I., et al., Treatment of metastatic prostatic cancer with low-dose prednisone:
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55. Nishimura, K., et al., *Potential mechanism for the effects of dexamethasone on growth of* androgen-independent prostate cancer. J Natl Cancer Inst, 2001. 93(22): p. 1739-46.  
56. Li, Z., et al., Glucocorticoid up-regulates transforming growth factor-beta (TGF-beta) type II
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57. Tannock, I.F., et al., Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol, 1996. 14(6): p. 1756-64.  
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| Karnofsky Performance Scale   |                                                                                                                       |
|-------------------------------|-----------------------------------------------------------------------------------------------------------------------|
| %                             | Description                                                                                                           |
| 100                           | Normal, no complaints, no  evidence of disease Able to carry on normal  activity, minor signs or  symptoms of disease |
| 90                            | Normal activity with effort,  some signs or symptoms of  disease                                                      |
| 80                            | Cares for self, unable to carry  on normal activity or to do  active work                                             |
| 70                            | Requires occasional assistance  but is able to care for most  needs                                                   |
| 60                            | Requires considerable  assistance and frequent  medical care                                                          |
| 50 40                         | Disabled, requires special care and assistance Severely disabled,  hospitalization indicated.  Death not imminent.    |
| 30                            | Very sick, hospitalization  indicated. Death not  imminent.                                                           |
| 20 10                         | Moribund, fatal processes  progressing rapidly                                                                        |
| 0                             | Dead                                                                                                                  |  
APPENDIX 1: PERFORMANCE STATUS CRITERIA
12.2.1 evaluation of target lesions
appendix 2 cyp450 isoenzyme inhibitors

| Strong CYP3A4,5,7 inhibitors                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             | Moderate CYP3A 4,5,7 inhibitors   | CYP3A4 inducers   |
|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------|-------------------|
| Clarithromycin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           | Amprenavir                        | Avasimibe         |
| Conivaptan                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               | Aprepitant                        | Bosentan          |
| grapefruit juice                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         | Atazanavir                        | Carbamazepine     |
| Indinavir                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                | Cimetidine                        | Efavirenz         |
| Itraconazole                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             | Modafinil                         |                   |
| Ketoconazole                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             | Darunavir                         | Nafcillin         |
| Lopinavir                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                | Diltiazem                         | Oxcarbazepine     |
| Mibefradil                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               | Elvitegravir                      | Phenobarbital     |
| Nefazodone                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               | Erythromycin                      | Phenytoin         |
| Nelfinavir                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               | Fluconazole                       | pioglitazone      |
| Posaconazole                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             | Fosamprenavir                     | Rifabutin         |
| Ritonavir                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                | Tofisopam                         | Rifampin          |
| Saquinavir                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               | Tipranavir                        | St. John's wort   |
| Telithromycin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            | Verapamil                         | Topiramate        |
| Troleandomycin Voriconazole This database of CYP inhibitors was compiled from the Indiana University School of Medicine's "Clinically Relevant" Table and from the  University of Washington's Drug Interaction Database based on in vitro studies. Strong inhibitors are predicted to increase Abiraterone acetate  AUC > 5-fold, and moderate inhibitors are predicted to increase Abiraterone AUC ≥ 2-fold but < 5-fold.  This database of CYP inducers was compiled from the FDA's "Guidance for Industry, Drug Interaction Studies;" from the Indiana University  School of Medicine's "Clinically Relevant" Table; and from (Pursche et al. 2008). |                                   |                   |
12.2.1 evaluation of target lesions
cyp450 substrates to be used

| CYP2C8                                                                                                                                                    | CYP2C9        | CYP2C19          | CYP3A4,5,7**   |               |
|-----------------------------------------------------------------------------------------------------------------------------------------------------------|---------------|------------------|----------------|---------------|
| amodiaquine                                                                                                                                               | celecoxib     | amitriptyline    | Adinazolam     | fentanyl2     |
| cerivastatin                                                                                                                                              | diclofenac    | citalopram       | alfentanil1,2  | flunitrazepam |
| pioglitazone                                                                                                                                              | flurbiprofen  | clobazam         | alphadihydroergocryptine1                | fluticasone1  |
| repaglinide                                                                                                                                               | fluvastatin   | clomipramine     | alprazolam     | lovastatin1   |
| rosiglitazone                                                                                                                                             | glibenclamide | clopidogrel      | amlodipine     | maraviroc1    |
| (glyburide)                                                                                                                                               |               |                  |                |               |
| torsemide                                                                                                                                                 | gliclazide    | diazepam         | aripiprazole   | midazolam1    |
| troglitazone                                                                                                                                              | glimepiride   | fluoxetine       | atorvastatin   | nifedipine    |
| glipizide                                                                                                                                                 | imipramine    | brotizolam1      | nisoldipine    |               |
| indomethacin                                                                                                                                              | lansoprazole  | budesonide1      | nitrendipine   |               |
| irbesartan                                                                                                                                                | moclobemide   | buspirone1       | perospirone1   |               |
| ketobemidone                                                                                                                                              | omeprazole    | cerivastatin     | quinine        |               |
| lornoxicam                                                                                                                                                | pantoprazole  | chlorpheniramine | sildenafil1    |               |
| losartan                                                                                                                                                  | progesterone  | cyclosporine2    | simvastatin1   |               |
| meloxicam                                                                                                                                                 | propranolol   | darifenacin1     | sirolimus1,2   |               |
| naproxen                                                                                                                                                  | quazepam      | Diazepam         | tipranavir1    |               |
| nateglinide                                                                                                                                               | rabeprazole   | diergotamine2    | trazodone      |               |
| piroxicam                                                                                                                                                 | sertraline    | ebastine1        | triazolam1     |               |
| S-ibuprofen                                                                                                                                               | S-mephenytoin | eletriptan1      |                |               |
| sulfamethoxazole                                                                                                                                          | eplerenone1   |                  |                |               |
| tenoxicam                                                                                                                                                 | ergotamine2   |                  |                |               |
| tolbutamide                                                                                                                                               | Estazolam     |                  |                |               |
| torsemide                                                                                                                                                 | everolimus1   |                  |                |               |
| valdecoxib                                                                                                                                                |               |                  |                |               |
| * This database of CYP substrates was compiled from the Indiana University School of Medicine's "Clinically Relevant" Table, and from  (Zhou et al. 2009) |               |                  |                |               |  
* This database of CYP substrates was compiled from the Indiana University School of Medicine's "Clinically Relevant" Table, and from
(Zhou et al. 2009)
** CYP3A4,5,7 substrates were compiled from the Indiana University School of Medicine's "Clinically Relevant" Table; and supplemented by the FDA's "Guidance for Industry, Drug Interaction Studies" and the University of Washington's Drug Interaction Database.  
1 Sensitive substrates: Drugs whose plasma AUC values have been shown to increase 5-fold or higher when co-administered with a potent inhibitor of the respective enzyme.  
2 Substrates with narrow therapeutic index (NTI): Drugs whose exposure-response indicates that increases in their exposure levels by the concomitant use of potent inhibitors may lead to serious safety concerns (e.g., Torsades de Pointes).
12.2.1 evaluation of target lesions
appendix 3 nci common toxicity

NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 can be found here: http://evs.nci.nih.gov/ftp1/CTCAE/About.html
12.2.1 evaluation of target lesions
appendix 4 criteria for disease

| Variable                                                                                                                | Assessments                                                                                                                                                                                                                                                                                                            | Progression                                                                                                                                                                                                       |
|-------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Soft-tissue lesions                                                                                                     | Use RECIST 1.1 criteria, except:  Only report changes in lymph  nodes that were ~2 cm in  diameter at baseline  Record changes in nodal and  visceral soft tissue sites separately  Record complete elimination of  disease at any site separately  Confirm favorable change with  next planned scan 8 weeks later | Use RECIST 1.1 criteria for progression, except:   Progression at first assessment must be confirmed by a second scan 6-8  weeks later (For some treatments, a lesion may increase in size  before it decreases) |
| Bone                                                                                                                    | Record as either new lesions or  no new lesions                                                                                                                                                                                                                                                                        | The appearance of ≥ 2 new lesionsAND A confirmatory scan 6-8 weeks later showing at  least 2 additional new lesions                                                                                               |
| If no new lesions, continue therapy If new lesions: continue therapy but  perform a confirmatory scan 6-8 weeks  later. | The date of progression is the date of the first  scan that shows the change                                                                                                                                                                                                                                           |                                                                                                                                                                                                                   |
| If confirmatory scan has no new lesions,  continue therapy. If there are additional new lesions, this is progression.   |                                                                                                                                                                                                                                                                                                                        |                                                                                                                                                                                                                   |
| Symptoms                                                                                                                | Consider independently of other outcome measures One or more of the following criteria indicates disease progression:  Need for new systemic therapy  Need for palliative radiation therapy  Development of a new skeletal-related event                                                                            |                                                                                                                                                                                                                   |