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Date Printed: September 30, 2014: 05:52 PM

Private Property of Blue Cross and Blue Shield of Florida.
This medical policy (medical coverage guideline) is Copyright 2014, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2014 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

09-J0000-94

Original Effective Date: 04/15/09

Reviewed: 07/09/14

Revised: 08/15/14

Subject: Human EGFR Inhibitors (Cetuximab [Erbitux], Panitumumab [Vectibix])

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

Position Statement

Dosage/ Administration

Billing/Coding

Reimbursement

Program Exceptions

Definitions

Related Guidelines

Other

References

Updates

Decision Tree

Previous Information

DESCRIPTION:

Cetuximab (Erbitux) and panitumumab (Vectibix) are human monoclonal antibody that target epidermal growth factor receptor (EGFR, also known as HER-1). EGFR is expressed in many normal epithelial tissues, including the skin and hair follicle. Over expression of EGFR has been detected in many human cancers including those of the head and neck, colon and rectum. Excessive activation of EGFR is associated with advanced stages of cancer and a poor prognosis.

In contrast to small molecule tyrosine kinase inhibitors (e.g., imatinib [Gleevec]) that inhibit EGFR by interfering with ATP binding, cetuximab and panitumumab block the EGFR receptor on both normal and cancerous cells. This binding blocks phosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, and decreased survival of tumor cells that express the EGFR.

POSITION STATEMENT:

I. Cetuximab (Erbitux®) IV meets the definition of medical necessity when used to treat the indications listed in table 1, all of the indication-specific criteria are met, and the dose does not exceed either of the following:

• 400 mg/m2 initially

• 250 mg/m2 every 7 days

Table 1:

Indications and Specific Criteria

Indication

Criteria

Colorectal cancer

KRAS gene is normal (i.e., without mutation, also known as wild type)

Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Cetuximab will be used in one of the following settings

1. Treatment of locally or regionally advanced disease in combination with radiotherapy

2. Treatment of recurrent, unresectable disease persistent disease

Non-melanoma carcinoma of the skin

Member has a basal or squamous cell skin cancer that is recurrent or metastatic

Non-small cell lung cancer (NSCLC)

When used as first line therapy for advanced or metastatic disease

Approval duration: 6 months

II. Panitumumab (Vectibix®) IV meets the definition of medical necessity when used to treat either of the following indications:

A. Colorectal Cancer and BOTH of the following:

1. KRAS gene is normal (i.e., without mutation, also known as wild type).

2. Dosage does not exceed 6 mg/kg every 14 days.

B. Penile Cancer and BOTH of the following:

1. Single-agent therapy for second-line treatment of metastatic disease.

2. Dosage does not exceed 6 mg/kg every 14 days.

Approval duration: 6 months

III. Cetuximab meets the definition of medical necessity when used to treat the following designated Orphan Drug indication (http://www.fda.gov/orpha/desinat/list.htm) when the dose does not exceed the maximum FDA-approved dose:

• Pancreatic Cancer

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

FDA-approval:

• Cetuximab: cetuximab is FDA-approved for treatment of head and neck cancer and colorectal cancer in the following settings

o Head and Neck Cancer

− Locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy.

− Recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with 5-FU.

− Recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy.

o Colorectal Cancer: KRAS mutation-negative (wild-type), EGFR-expressing, metastatic colorectal cancer as determined by FDA-approved tests

− in combination with FOLFIRI for first-line treatment,

− in combination with irinotecan in patients who are refractory to irinotecan-based chemotherapy,

− as a single agent in patients who have failed oxaliplatin- and irinotecan-based chemotherapy or who are intolerant to irinotecan

o Prior to cetuximab therapy, members should be pre-medicated with a histamine-receptor antagonist. The recommended dose is 400 mg/m2 initially as an intravenous (IV) infusion over 120 minutes followed by 250 mg/m2 weekly IV over 60 minutes.

o Cetuximab should be initiated one week prior to initiation of radiation therapy

o Cetuximab administration should be completed 1 hour prior to platinum-based therapy with 5-FU and FOLFIRI.

• Panitumumab: indicated for the treatment of patients with wild-type KRAS (exon 2 in codons 12 or 13) metastatic colorectal cancer (mCRC) as determined by an FDA-approved test for this use:

o As first-line therapy in combination with FOLFOX

o As monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy. Panitumumab is not indicated for treatment of persons with KRAS mutation-positive mCRC or for persons who KRAS mCRC status is unknown.

o The recommended dose is 6 mg/kg every 14 days. Panitumumab should be administered as an IV infusion over 60 minutes (doses of 1000 mg or less) or 90 minutes (doses greater than 1000 mg).

o Infusion reactions may occur; appropriate medical resources for the treatment of infusion reactions should be available.

Drug Availability

• Cetuximab is supplied as 100 mg/50 mL and 200 mg/100 mL single-use vials.

• Panitumumab is supplied as 100 mg/5 mL, 200 mg/10 mL, and 400 mg/20 mL single-use vials.

PRECAUTIONS:

Boxed Warning

• Cetuximab

o Serious infusion reactions may occur. Immediately stop and permanently discontinue cetuximab if a serious reaction occurs.

o Cardiopulmonary arrest and/or sudden death have been reported by persons administered cetuximab. Closely monitor serum electrolytes, including serum magnesium, potassium, and calcium, during and after cetuximab administration

• Panitumumab

o Dermatologic toxicities may occur. Withhold or discontinue panitumumab if severe or life-threatening complications occur. Limit sun exposure

o Serious infusion reactions may occur. Immediately stop and permanently discontinue panitumumab if a serious reaction occurs.

Warnings and Precautions

• Cetuximab

o Pulmonary Toxicity: Interrupt therapy for acute onset or worsening of pulmonary symptoms.

o Dermatologic Toxicity: Limit sun exposure. Monitor for inflammatory or infectious sequelae.

o Hypomagnesemia: Periodically monitor during and for at least 8 weeks following the completion of cetuximab. Replete electrolytes as necessary.

• Panitumumab

o Increased Mortality or Toxicity when panitumumab is used in combination with chemotherapy

o Pulmonary Fibrosis/Interstitial Lung Disease (ILD): Permanently discontinue panitumumab in persons developing ILD.

o Electrolyte Depletion/Monitoring: Monitor electrolytes during and for 8 weeks after completion of panitumumab therapy and institute appropriate treatment.

o Ocular Toxicities: Monitor for evidence of keratitis or ulcerative keratitis. Interrupt or discontinue panitumumab for acute or worsening keratitis

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding:

J9055

Injection, cetuximab,10mg

J9303

Injection, panitumumab,10mg

ICD-9 Diagnoses Codes That Support Medical Necessity for J9055 (cetuximab):

140.0 – 140.9

Malignant neoplasm of lip

141.0 – 141.9

Malignant neoplasm of tongue

143.0 – 143.9

Malignant neoplasm of gum

144.0 – 144.9

Malignant neoplasm of floor of mouth

145.0 – 145.9

Malignant neoplasm of other and unspecified parts of mouth

146.0 – 146.9

Malignant neoplasm of oropharynx

148.0 – 148.9

Malignant neoplasm of hypopharynx

149.0 – 149.9

Malignant neoplasm of other and ill-defined sites within the lip, oral cavity, and pharynx

152.0-152.2

Malignant neoplasm of duodenum, jejunum, ileum

152.8

Malignant neoplasm of other specified sites of small intestine

152.9

Malignant neoplasm of small intestine, unspecified site

153.0 – 153.9

Malignant neoplasm of colon

154.0 – 154.8

Malignant neoplasm of rectum, rectosigmoid junction, and anus

160.2

Malignant neoplasm of maxillary sinus

160.3

Malignant neoplasm of the ethmoidal sinus (Squamous cell carcinoma of the head and neck (SCCHN))

161.0 – 161.9

Malignant neoplasm of larynx

162.0 – 162.9

Malignant neoplasm of trachea, bronchus, and lung

173.00

Unspecified malignant neoplasm of the skin of the lip

173.01

Basal cell carcinoma of skin of lip

173.02

Squamous cell carcinoma of skin of lip

173.09

Other specified malignant neoplasm of skin of lip

173.12

Squamous cell carcinoma of eyelid, including canthus

173.22

Squamous cell carcinoma of skin of ear and external auditory canal

173.32

Squamous cell carcinoma of skin of other and unspecified parts of face

173.42

Squamous cell carcinoma of scalp and skin of neck

173.52

Squamous cell carcinoma of skin of trunk, except scrotum

173.62

Squamous cell carcinoma of skin of upper limb, including shoulder

173.72

Squamous cell carcinoma of skin of lower limb, including hip

173.82

Squamous cell carcinoma of other specified sites of skin

173.92

Squamous cell carcinoma of skin, site unspecified

195.0

Malignant neoplasm of other and ill-defined sites of head, face, and neck (Squamous cell carcinoma of the Head and Neck (SCCHN))

197.0

Secondary malignant neoplasm of lung

197.6

Secondary malignant neoplasm of retroperitoneum and peritoneum

197.7

Malignant neoplasm of liver secondary

235.1

Neoplasm of uncertain behavior of digestive and respiratory systems; lip, oral cavity, and pharynx (Squamous cell carcinoma of the head and neck (SCCHN))

235.6

Neoplasm of uncertain behavior of digestive and respiratory systems; larynx (Squamous cell carcinoma of the head and neck (SCCHN))

235.9

Neoplasm of uncertain behavior of other and unspecified respiratory organs

V10.01

Personal history of malignant neoplasm of tongue

V10.02

Personal history of malignant neoplasm of other and unspecified oral cavity and pharynx

V10.05

Personal history of malignant neoplasm of large intestine

V10.11

Personal history of malignant neoplasm of bronchus and lung

V10.21

Personal history of malignant neoplasm of larynx

V10.22

Personal history of malignant neoplasm of nasal cavities, middle ear, and accessory sinuses

V10.83

Personal history of other malignant neoplasm of skin

ICD-10 Diagnoses Codes That Support Medical Necessity for J9055 (cetuximab): (Effective 10/01/15)

C00.0 – C07

Malignant neoplasm of lip, base of tongue, of other and unspecified parts of tongue, gum, floor of mouth, palate, of other and unspecified parts of mouth, and parotid gland.

C09 – C10.9

Maligant neoplasm of tonsil and oropharynx

C12.0 – C14.8

Malignant neoplasm of piriform sinus, hypopharynx and other and ill-defined sites in the lip, oral cavity and pharynx.

C17.0-17.2

Malignant neoplasm of duodenum, jejunum, ileum

C17.8

Malignant neoplasm of overlapping sites of small intestine

C17.9

Malignant neoplasm of small intestine, unspecified

C18.0 – C21.8

Malignant neoplasm of colon, rectosigmoid junction, rectum and anus and anal canal

C31.0

Malignant neoplasm of maxillary sinus

C31.1

Malignant neoplasm of ethmoidal sinus

C32.0 – C34.92

Malignant neoplasm of larynx, trachea, bronchus and lung

C44.0

Malignant neoplasm of skin of lip

C44.01

Basal cell carcinoma of skin of lip

C44.02

Squamous cell carcinoma of skin of lip

C44.09

Other specified malignant neoplasm of skin of lip

C44.121

Squamous cell carcinoma of skin of unspecified eyelid, including canthus

C44.221

Squamous cell carcinoma of skin of unspecified ear and external auricular

C44.320

Squamous cell carcinoma of skin of unspecified parts of face

C44.321

Squamous cell carcinoma of skin of nose

C44.329

Squamous cell carcinoma of skin of other parts of face

C44.42

Squamous cell carcinoma of skin of scalp and neck

C44.520

Squamous cell carcinoma of anal skin

C44.521

Squamous cell carcinoma of skin of breast

C44.529

Squamous cell carcinoma of skin of other part of trunk

C44.621

Squamous cell carcinoma of skin of unspecified upper limb, including shoulder

C44.721

Squamous cell carcinoma of skin of unspecified lower limb, including hip

C44.82

Squamous cell carcinoma of overlapping sites of skin

C44.92

Squamous cell carcinoma of skin, unspecified

C49.9

Malignant neoplasm of connective and soft tissue, unspecified

C72.1

Malignant neoplasm of cauda equina

C76.0

Malignant neoplasm of head, face and neck

C78.00

Secondary malignant neoplasm of unspecified lung

C78.6

Secondary malignant neoplasm of retroperitoneum and peritoneum

C78.7

Secondary malignant neoplasm of liver and intrahepatic bile duct

D37.01

Neoplasm of uncertain behavior of lip

D37.02

Neoplasm of uncertain behavior of tongue

D37.04

Neoplasm of uncertain behavior of the minor salivary glands

D37.05

Neoplasm of uncertain behavior of pharynx

D38.0

Neoplasm of uncertain behavior of larynx

D38.5

Neoplasm of uncertain behavior of other respiratory organs

D38.6

Neoplasm of uncertain behavior of respiratory organ, unspecified

Z85.038

Personal history of other malignant neoplasm of large intestine

Z85.118

Personal history of other malignant neoplasm of bronchus and lung

Z85.21

Personal history of malignant neoplasm of larynx

Z85.22

Personal history of malignant neoplasm of nasal cavities, middle ear, and accessory sinuses

Z85.810

Personal history of malignant neoplasm of tongue

Z85.818

Personal history of malignant neoplasm of other sites of lip, oral cavity, and pharynx

Z85.819

Personal history of malignant neoplasm of unspecified site of lip, oral cavity, and pharynx

Z85.828

Personal history of other malignant neoplasm of skin

ICD-9 Diagnoses Codes That Support Medical Necessity for J9303 (panitumumab):

152.0-152.2

Malignant neoplasm of duodenum, jejunum, ileum

152.8

Malignant neoplasm of other specified sites of small intestine

152.9

Malignant neoplasm of small intestine, unspecified site

153.0 – 153.9

Malignant neoplasm of colon

154.0

Malignant neoplasm of recto sigmoid junction

154.1

Malignant neoplasm of rectum

154.8

Malignant neoplasm of other sites of rectum recto sigmoid junction and anus

187.1 – 187.4

Malignant neoplasm of penis and other male genital organs

187.8

Other specified sites of male genital organs

187.9

Male genital organ, site unspecified

197.0

Secondary malignant neoplasm of lung

197.6

Secondary malignant neoplasm of retroperitoneum and peritoneum

197.7

Malignant neoplasm of liver secondary

V10.05

Personal history of malignant neoplasm of large intestine

ICD-10 Diagnoses Codes That Support Medical Necessity for J9303 (panitumumab): (Effective 10/01/15)

C17.0-17.2

Malignant neoplasm of duodenum, jejunum, ileum

C17.8

Malignant neoplasm of overlapping sites of small intestine

C17.9

Malignant neoplasm of small intestine, unspecified

C18.0 – C21.8

Malignant neoplasm of colon, rectosigmoid junction, rectum, anus and anal canal

C60.0 – C60.9

Malignant neoplasm of penis

C63.7

Malignant neoplasm of other specified male genital organs

C63.8

Malignant neoplasm of overlapping sites of male genital organs

C63.9

Malignant neoplasm of male genital organ, unspecified

C78.00 – C78.89

Secondary malignant neoplasm of respiratory and digestive organs

Z85.038

Personal history of other malignant neoplasm of large intestine

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Advantage Products: No National Coverage Determination (NCD) was found at the time of the last guideline revised date. The following Local Coverage Determination (LCD) was reviewed on the last guideline revised date: Cetuximab (Erbitux), (L29097) located at fcso.com.

DEFINITIONS:

Apoptosis: A state in which a cell has ceased replication and is in the process of programmed cell death.

EGFR: The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is the cell-surface receptor for members of the epidermal growth factor family (EGF-family) of extracellular protein ligands. The epidermal growth factor receptor is a member of the ErbB family of receptors, a subfamily of four closely related receptor tyrosine kinases: EGFR (ErbB-1), HER2/c-neu (ErbB-2), Her 3 (ErB-3) and Her 4 (ErB-4). Mutations affecting EGFR expression or activity could result in cancer.

FOLFOX: combination chemotherapy consisting of the following agents; leucovorin, fluorouracil, oxaliplatin.

FOLFIRI: combination chemotherapy consisting of the following agents; leucovorin, fluorouracil, irinotecan.

RELATED GUIDELINES:

Analysis of Human DNA in Stool Samples as a Technique for Colorectal Cancer Screening, 05-82000-27
Bevacizumab (Avastin®) Injection, 09-J0000-66

Carboplatin (Paraplatin®) IV, 09-J0000-93

Docetaxel (Taxotere®s) IV, 09-J0000-95

Gemcitabine (Gemzar®), 09-J0000-96

KRAS Mutation Analysis, 05-86000-28

Oxaliplatin (Eloxatin®) IV, 09-J1000-00

Paclitaxel and Paclitaxel (protein-bound) IV, 09-J1000-05

Topotecan HCl (Hycamtin®) IV, 09-J1000-02

Vinorelbine Tartrate (Navelbine®) IV, 09-J1000-03

OTHER:

TABLE 1

ECOG PERFORMANCE STATUS

Grade

ECOG

0

Fully active, able to carry on all pre-disease performance without restriction

1

Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work

2

Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours

3

Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours

4

Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair

5

Dead

REFERENCES:

1. Cetuximab. In McEvoy GK, editor. AHFS drug information 2014 [monograph on the internet]. Bethesda (MD): American Society of Health-System Pharmacists; 2014 [cited 2014 June 10].

2. Clinical Pharmacology. [database online]. Tampa, FL: Gold Standard, Inc.; 2012. URL. www.Clinicalpharamcology-ip.com Accessed 6/10/14.

3. Erbitux (cetuximab) [package insert]. Bristol-Myers Squibb Co. Princeton (NJ): August 2013.

4. Micromedex ® Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed 6/10/14.

5. National Comprehensive Cancer Network. Cancer Guidelines. Cancer Guidelines and Drugs and Biologics Compendium. Accessed 6/10/14.

6. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Version 1.2013. Basal cell and Squamous Cell Skin Cancers. Available at http://www.nccn.org/professionals/physician_gls/PDF/nmsc.pdf Accessed 6/12/13

7. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Version 2.2013. Head and Neck Cancers. Available at http://www.nccn.org/professionals/physician_gls/PDF/head-and-neck.pdf Accessed 6/11/2013

8. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Version 2.2013. Non-Small Cell Lung Cancer. Accessed 6/12/13

9. Panitumumab. In McEvoy GK, editor. AHFS drug information 2014 [monograph on the internet]. Bethesda (MD): American Society of Health-System Pharmacists; 2014 [cited 2014 Jun 10].

10. Vectibix (panitumumab) [package insert]. Amgen Inc. Thousand Oaks (CA): March 2014.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 07/09/14.

GUIDELINE UPDATE INFORMATION:

04/15/09

New Medical Coverage Guideline.

05/15/09

Revision to guideline; consisting of adding panitumumab coverage criteria, updating ICD-9 codes for cetuximab, changing name and updating references.

10/15/09

Revision to guideline; consisting of clarifying dosage.

04/15/10

Revision to guideline; consisting of updating codes.

08/01/10

Revision to guideline; consisting of updating codes.

09/15/10

Review and revision to guideline; consisting of updating coding and references.

09/15/11

Review and revision to guideline; consisting of updating coding and references.

10/01/11

Revision to guideline; consisting of updating codes.

09/15/12

Review and revision to guideline; consisting of updating position statement, precautions, coding and references.

12/15/12

Revision to guideline; consisting of updating coding.

09/15/13

Review and revision to guideline; consisting of revising and reformatting position statement; revising description, dosage/administration and precautions sections; updating references, program exceptions, and coding.

02/15/14

Revision to guideline; consisting of removing chordoma indication.

08/15/14

Review and revision to guideline; consisting of reformatting position statement, updating dosage/administration and references.

Private Property of Blue Cross and Blue Shield of Florida.
This medical policy (medical coverage guideline) is copyright 2013, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2013 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association.The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

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Date Printed: September 30, 2014: 05:52 PM