Exhibit 99.5
Quadramet in Osteosarcoma
Peter Anderson, MD, PhD
Professor of Pediatrics
The M D Anderson Cancer Center
Houston, TX
Pete Anderson MD, PhD
pmanders@mdanderson.org
Slide # 2
Osteosarcoma - Introduction
Malignant tumor in bone (forms bone)
Location: Long bones> other
Current therapy plateau
Challenges to improve therapy
Why Quadramet for osteosarcoma?
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Osteosarcoma:
Bone Scans Show this
Tumor Makes Bone
High uptake of 99mTc MDP
= high 153Sm-EDTMP
(Quadramet) uptake
So when see a “hot bone scan”,
should THINK about Quadramet
Slide # 4
[Picture of Doctor with male patient]
Osteosarcoma patient, aka “the Guitarist”, recently treated with Quadramet
Current Therapy of Osteosarcoma: Upfront
Chemotherapy before surgery (pre-adjuvant): cisplatinum (intraarterial at MD Anderson), doxorubicin, high-dose methotrexate
Local control surgery
Additional chemotherapy (same as initial if tumor kill >95%; sometimes ifosfamide)
Slide # 1
Osteosarcoma: Metastatic
Similar therapy as non-metastatic, but often also with ifosfamide, too
Local control difficult- lung surgery for lung metastases; radiation or surgery for bone metastases (?Quadramet)
Principles learned in can be applied to other cancers with osteoblastic metastases.
Slide # 2
Problems with Current Therapy
of Osteosarcoma
(Opportunities to Improve)
Chemotherapy toxicity:
Whole body treated, not just bone tumor
Mouth sores, poor nutrition
Hospitalizations for fevers + low wbc counts common
Plateau: 60-65% survival
Need increased speed and completeness of response to improve survival
Slide # 3
Opportunities in Osteosarcoma: Quadramet
Treatment of primary
Isolated limb perfusion (like local high dose w/o marrow toxicity)
Treatment of metastatic
Quadramet + gemcitabine (radiosensitizer)
Slide # 1
Quadramet: A Targeted Drug for Osteosarcoma (SPECIFIC!)
This cancer makes bone
Ratio of Quadramet in tumor:organ extremely HIGH (>700:1 bone:lung)
Bone scan, a commonly used clinical tool, is predictive of very specific uptake
99Tc-MDP chemistry of metabolism of tracer into bone is same as 153Sm-EDTMP
“One picture is worth a thousand words”
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Now s/p
2 doses
Quadramet
And RT.
-Working 2
jobs!
Osteosarcoma
Metastatic to
Sacrum
Severe leg pain
from sacral
metastasis
[Picture of Female Patient]
Experience with Quadramet in Osteosarcoma
High-dose Quadramet: dose escalation
High-dose Quadramet with Gemcitabine (radio-sensitization)
Standard dose Quadramet with Gemcitabine radio-sensitization
Future studies (ILP; aerosol chemo)
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High Dose Quadramet
Dose limiting toxicity on marrow can be overcome with stem cells
Dose escalated 30x safely (30 mCi/kg)
Large doses of radiation (20,000 cGy) provided to tumor (and not other organs)
Anderson et al. High-dose samarium-Low toxicity of skeletal irradiation in patients with osteosarcoma and bone metastases. J. Clinical Oncology. 2002;20:189-196
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High-Dose Quadramet
+ Gemcitabine
Gemcitabine, a potent radiosensitizer, was given 1 day after Quadramet
New paradigm:
Bind radioisotope to target, then use radiosensitizer
Improved responses (bone/PET)
ASCO 2005;
Anderson et al. Gemcitabine radiosensitization after high-dose samarium for osteoblastic osteosarcoma.
Clinical Cancer Research Oct. 2005
Slide # 6
Bone
Scans
Samarium
+ Gemzar
SYNERGY
After
Quadramet
+ Gemzar
BEFORE
Quadramet
+ Gemzar
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After
Before
Slide # 8
Quadramet
(day 1)
Unbound:
Eliminated
in urine (6 hr)
Bone metastases >> skeleton>>>> organs
( STRONG binding to “new” bone)
continuous radiation to cells near new bone
Gemcitabine
Radiosensitization (day 2)
IMPROVED kill of cells
near Quadramet
Slide # 1
Standard Dose Quadramet
+ Gemcitabine
Initial use
People that cannot harvest stem cells
Current use
Provide repeated doses with more effective tumor kill
Limitation
Time to recovery of platelets (4-8 weeks)
Most doses given so far: 8
(4-12 weeks apart)
Slide # 2
PET w/o Activity in tumor deposits
Slide # 4
After Samarium +
Gemcitabine
dose 5
After Samarium +
Gemcitabine
dose 8
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After Samarium
+ Gemcitabine
dose 5 (of 8)
Slide # 6
End of therapy
6 months after
end of therapy
Slide # 7
“RESIST using RECIST”
(Especially True in Bone and Sarcomas)
Bob Benjamin (Head MDACC, Dept. of Sarcoma) at SARC meeting 5/05
Why?- Size change (CT or MRI) is the least sensitive indication of response. (GIST experience)
Better (more useful to patient): PET/CT (change in SUV), bone scan (quantitative), dynamic MRI (blood supply), Time to Progression (TTP) .
Slide # 8
Repeated doses of Quadramet
+ Gemcitabine
Possible
Safe
Probably best used with other modalities of control
external beam RT, proton beam RT
chemotherapy (HDMTX), Avastin, Doxil
Slide # 1
Example: HDMTX, then
Samarium+ Gemcitabine
6/13/05
8/24/05
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6/13/05
HDMTX, then
Quadramet + gemcitabine - PET shows
improvement in refractory osteosarcoma!
8/24/05
Slide # 3
Excellent QOL s/p Quadramet+ Gemcitabine QOL
[Picture of Female Patient]
Quadramet
+ Radiosenzitizer
Isolated limb perfusion (cisplatin as the radiosensitizer)
Canine studies ongoing at Colorado State University Animal Cancer Center (N. Erhart DVM)
Dogs with osteosarcoma
Goal: more rapid control of osteosarcoma primary
With Proton beam radiotherapy (2006 at MD Anderson Cancer Center)
Goal: treatment of metastatic bone or lung lesions that require improved cancer control (e.g surgery not possible or enough!)
Slide # 1
Quadramet in Osteosarcoma: Summary
Studies in osteosarcoma, a bone forming tumor, have provided insights about how to use Quadramet more effectively
High-dose studies show safety
Radiosensitization studies indicate repeated dose schedules and synergy with other cancer control measures [e.g. HDTMX, gemcitabine, RT (esp. proton therapy)] may improve control of osteosarcoma (and bone metastases)
Slide # 2
MD Anderson Proton Therapy Center
($125 M Investment in Radiotherapy)
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Questions?
Pete Anderson MD, PhD
Direct line 713-563-0893
pmanders@mdanderson.org
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