Novartis Pharmaceuticals Corporation

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East Hanover, NJ 07936

 

 

Appendix 6:
Summary of ONJ Cases from Retrospective Chart Review at MD
Anderson Cancer Center

 

 

Zometa® (zoledronic acid) Injection

and

Aredia® (pamidronate disodium) Injection

Submitted:  February 1, 2005

 

 

Oncologic Drugs Advisory Committee Meeting

March 4, 2005

 

 

Property of Novartis Pharmaceuticals Corporation
All rights reserved
Available for public disclosure without redaction

 

 


Summary of ONJ Cases from Retrospective Chart Review at MD Anderson Cancer Center

 

ID

 

Gender/
Age

Diagnosis

Date of DX

BP (Type/#)

Date of DX ON

BP Duration (mos)

Predisposing factors

Clinical presentation

Onco Treatments

1

(A)

F/54

MTC, hypothyroidism

12/97

 

Bone mets 5/99

Aredia 4/00 qmo

In 2003 was on Zometa (date N/A)

Rx’d in Georgia

01/03

33mos

 

A: 33mos

(Z: N/A)

Trauma to jaw/anesthesia in 12/02

Trauma never healed

10/03 pain right mandible with exposed bone

Progressive with extension to maxilla

DTIC

Anti-CEA antibody/Adria

2

(AZ)

M/58

MM, COPD, HTN, DM, smoking

10/96

MDA pharmacy

A - 1/98-2/02 

Z - 3/02-9/04

09/02

57 mos

 

A: 50 mos

 

Z: 7 mos

 

Gingivitis 6/02

Dental decay 6/02

Periodontal dz 6/02

Dental Extraction

7/02 (7 teeth)

Dentures XRT to maxilla 7/02

Right maxilla pain and poor healing/exposed bone 9/02

3/03 several areas of exposed bone

6/03 necrotic bone

9/03 larger areas 4x2 cm bilaterally + ant. bone exposure 1/x0.5 cm-debrid.

10/03, 11/03 debridements

Melphalan, prednisone, decadron hyper/cvad, interferon, thiothepa, busulfan, cyclophosphamide, thalidomide, arsenic autologous BMT X2

Ianoxin, vioxx, protonox, codeine, xanax, klonopin, prilosec, buspar, hydrocodone

3

(AZ)

F/79

MM, DVT, HTN

5/01

A – 5/01 – 6/02

Z – 7/02 – 4/04 *see CRF

8/03

26 mos

 

A: 13 mos

 

Z: 13 mos

Several dental extractions 9/02 Mandibular tori

Pain left mandible 8/03 (2x1 cm lesion)

Debridements 8/03, 10/03, 11/03, cephalexin, clindamycin,

1/04 worse ON 4/04 1/5 cm lesion

Melphalan, DEX, cyclophosphamide, cytoxan, thalidomide, coumadin, velcade, procrit, darbepoetin

4

(AZ)

F/47

MM, DM, Renal failure

3/97

A - ?

Z - ?

6/02

Unknown

Dental extraction in 6/01 tooth #20 left mandible

2/02 (outside MDA) – sequestrec-                                   

tomy to remove necrotic bone. Mod. Periodontal dz

Pain left mandible since 2/02

Panorex

6/02: lesion left mandible 2/03 debridement

3/03 hyperbaric O2 Rx

4/03 worsening of necrosis (1.5 cm)

9/03 stable

Hyper-CVAD (cytoxan, mesna, adryamycin, vincristine, decradron, cyclophosphamide, decardron, thalidomide, arsenic, melphalan, velcade.

5

(Z)

F/60

Breast ca, Bone mets 12/02

10/99

No A

Z – 5/03-7/03

5/04

Z: 2 doses

Latency 12 months

None

Pain right mandible/exposed bone (1x1cm)

Biopsy: necrotic bone

Sequestrectomy 5/04

Controlled with treatment

Aryamycin, Cyclophosphamide, Paclitaxel, Tamoxifen, Docetaxel, Arimidex, Exemestane, bellerga, xanax, elavil, melatonin, prilosec

6

(AZ)

F/70

Breast ca

1/30/98

A - 22 inf (90 mg q mo)

Z – 28 infus. (4mg q mo) 5/02

A – 8/00-4/02

Z – 5/02-9/04

(22 doses of A,  28 doses of Z

 

4/04

 

45 mos

 

 

A: 21 mos

 

Z: 24 mos

Dental extraction

Dentures

Pain right mandible, Poor healing, exposed bone – Infection?

5-FU, adryamycin, cyclophosphamide, tamoxifen, arimidex, exemestane, capecitabine, TAS-108, vinorelbine, gleevec, trastuzumab, paclitaxel 01/03-4/03, dexamethasone 10mg weekly 01/03

 

7

 

(AZ)

 

M/67

MM, osteoporosis

8/98

A-7/99 – 4/02

Z-6/02 – 9/04

2/04

53 mos

 

A: 32 mos

 

Z: 21 mos

Moderate periodontal disease

 

Mandibular Tori

6/99: good dentition

2/04 - pain right mandible: 3mmX4mm bone exposure

6/04: lesion healed

Hyper-CVAD (1/99) autologous BMT (6/99)

Serial dex 8/99

Thalidomide + dexamelphalan

Revimid

 

8

(Z)

F/42

Breast ca

9/98

Zometa started 10/03 with DX of bone mets

5/04

7 mos

 

Z: 7 mos

Dental extraction (1/04), Torus mandibularis, Slow healing and dry socket after extraction

Pain tooth #30, Poor healing, Infection, Bone exposure right mandible 5/04

Cytoxan, 5-Fu, methotrexate, tamoxifen, evista, adryamycin/ cytoxan, Taxol (7/03), Arimidex, Faslodex (5/7/04), Prozac, bextra, ambient, cipro, calcium, clindamycin, vicoprofen, XRT chest wall 1999, XRT mediastinum 12/01

9

 

(AZ)

 

9 cont.

F/44

Breast ca

10/99

A: 11/00 – 2/02

Z: [ED1] [ED2] 12/01 – 8/03

11/02

27 mos

 

 

A: 16 mos

 

Z: 11 mos

 

Mandibular Tori

12/99 – dental visit: mand. tori

11/02: pain right mandible – exposed bone

4/03: stable

10/03: stable

11/03: necrotic area larger

12/03: debridement

Paclitaxel, FAC, tamoxifen, Herceptin (11/02), navelbine, xeloda, dexamethasone (10/01

XRT: left hip, WBRT, Lspine, chest wall, axilla

10

(A)

M/60

MM

1/99

A: 1/99-4/00

5/99

4 mos

 

A: 4 mos

Bone exostosis, Dental extraction 5/99, Periodontal disease 5/99, smoking – 34 years

 

5/99: exposed bone after dental extraction (no pain) in maxilla and mandible; Treated with debridement and antibiotic: resolved 4/04.

Dexamethasone, Cytoxan, Melphalan, Holmium, Pepcid, Valium

11

(A)

F/61

Breast cancer

4/92

A : 3/99 – 12/01

Z: 4/02-5/03

8/00

17 mos

 

A: 17 mos

Dentures, Dental decay, Periodontal disease, Dental extraction 5/00 with poor healing

 

8/00: gum pain, exposed bone left mandible and maxilla

Controlled with treatment

FAC ’92, Methotrexate ’92, Vinblastine ’92, Tamoxifen 10/99, Exemestane 2/01, Fulvestrant 8/02, Megestrol 6/04, MVI, Celebrex, Hydrocodone

12

(AZ)

F/69

Breast ca, Melamona 1962, Bone mets 9/00

10/97

A: 11/00-7/02

Z:  8/02-9/04

11/04

46 mos

 

A: 21 mos

 

Z: 25 mos

Dental decay 5/04, Dental extraction 5/04

Poor healing after extraction, infection, no pain, exposed bone (11/04) left mandible

Tamoxifen 3/98, Anastrozole, Vioxx, Hydrocodone, Lasix, Bactrim, Clindamycin

13

(AZ)

F/46

Breast ca

7/01 Bone mets

A: 8/01-11/02

Z: 11/02-10/04

8/04

37 mos

 

A: 15 mos

 

Z: 22 mos

Gingivitis, advanced periodontal DZ, dental infection

8/04: pain right mandible, spontaneous bone exposure

Taxol 9/01, Herceptin 2/02, Taxoxifen 2/02, Prilosec, Decadron, Darvon

14

(AZ)

F/61

Breast ca, hypothyroidism

2/00 bone mets

A: 2/00-10/02 (~37 doses)

Z: 11/02-10/04 (~23 doses)

10/04

58 mos

 

A: 34 mos

 

Z: 24 mos

Gingivitis, Manipulation of right mandible, implants with poor healing and infection

4/04: right mandible pain – bone exposure

9/04: mand. implants removed, 10/04: 2X1x1.5cm bone exposure site, Healing well with irrigation, slicept

Tamoxifen, arimidex, celebrex

15

(Z)

F/71

MM, DM, Hyperlipidemia, ETOH use

1/00

Alendronate (4/00-11/01)

 

Z: 4/03, 7/03, 8/03, 11/03, 1/04

6/04

5 doses, latency 14 months

Dentures (traumatic wound)

Gum/jaw pain 4/04, Gingivitis, oseomyelitis, bone exposure

6/04: Eikenella corrodens, Rx’d

7/04: 2X1cm

8/04: debrid

11/04: 0.2X0.7cm

*steroids – induced diabetes

Dexamethasone 9/00, Valcade 4/03, Revimid 4/03, Interferon 9/00, Vioxx, Prevacid, Lortab, Zocor, Zoloft, Xanax, Neurontin

16

(AZ)

F/60

Breast ca, melanoma

5/80 bone mets

2/99 last visit to MDA: 9/04 (dead)

A: 3/99-10/01

Z: 12/01-6/04

12/03

56 mos

 

A: 31 mos

 

Z: 25 mos

Periodontal dz, Dental extraction 6/03, slow healing 7/03

*Rx’d with clindamycin, salicept, debridement

7/03 slow healing: debridement

8/03: debridement

12/03: bone exposure

2/04 dental at MDA: ONJ 2.5x2cm right mandible (biopsy proven)

¾ : 3/2 cm-debridement

¾ healing

5/04: debridement

6/04: healing  

XRT: chest, nodes, L-spine, and brain 7/04.

 

Taxotere 3/99, Cytoxan 3/99, Cyclophosphamide 3/99, Adriamycin 3/99, Tamoxifen 6/99, G-CSF 6/99, FEC 5/01, Xeloda 5/01, Aptosyn 5/01, Navelbine 8/01, Gemcitabine 8/01, Doxil 5/02, Faslodex 5/03, CPT-11 6/04, CMF 6/04, Augmentin, Cipro

17

(Z)

F/78

Breast ca, Osteoporosis, Atrial Arrhythmia, anemia

4/83 bone mets

8/02

Z: 9/02-1/05 (qmo)

10/04

26 mos

 

Z: 26 mos

 

Being treated outside MDA??

Femara, Tamoxifen, faslodex

18

(Z)

F/63

Breast ca, degenerative joint disease,asthma

10/02

bone mets 11/02

Z: started 4/03 outside MDACC

Last Zometa qmo. @MDACC 2/04

12/04

9 mos

 

Z: 9 mos

 

 

Periodontal disease and tooth extraction 2/04

Facial pain and swelling. Extraction of tooth root 10/04, pain/swelling and purulent drainage @ extraction site 12/04, poor fitting denture – trauma 12/04, osteomyelitis left maxilla 12/04.

Femara 10/02, Capecitabine 7/03, Adriamycin 1/04, Cytoxan 1/04, Fasoldex 7/04, Albuterol, Wellbutrin, Singular, Equagesic, Aleve and Cipro

 


 [ED1]Thi

 [ED2]This date is still in qustion as a start date as it would mean that A and Z were taken at the same time