Slide 1: Quadramet in Osteosarcoma
Quadramet in Osteosarcoma Peter Anderson, MD, PhD Professor of Pediatrics The M D Anderson Cancer Center Houston, TX
Slide 2: Pete Anderson MD, PhD
Pete Anderson MD, PhD pmanders@mdanderson.org
Slide 3: Osteosarcoma - Introduction
Osteosarcoma - Introduction Malignant tumor in bone (forms bone) Location: Long bones> other Current therapy plateau Challenges to improve therapy Why Quadramet for osteosarcoma?
Slide 4: Osteosarcoma: Bone Scans Show this Tumor Makes Bone
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 5: Osteosarcoma patient treated with Quadramet
[Picture of Doctor with male patient] Osteosarcoma patient, aka “the Guitarist”, recently treated with Quadramet
Slide 6: Current Therapy of Osteosarcoma: Upfront
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 7: Osteosarcoma: Metastatic
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 8: Problems with Current Therapy of Osteosarcoma
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 improv
Slide 9: Opportunities in Osteosarcoma: Quadramet
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 10: Quadramet: A Targeted Drug for Osteosarcoma
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-EDT
Slide 11: Now s/p doses Quadramet and RT
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]
Slide 12: Experience with Quadramet in Osteosarcoma
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)
Slide 13: High Dose Quadramet
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 osteosarc
Slide 14: High-Dose Quadramet + Gemcitabine
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 osteoblast
Slide 15: Bone Scans Samarium + Gemzar Synergy
Bone Scans Samarium + Gemzar SYNERGY After Quadramet + Gemzar BEFORE Quadramet + Gemzar
Slide 16: Before / After
CYTOGEN Before After
Slide 17: Quadramet and Gemcitabine radiosensitization mechanism
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 18: Standard Dose Quadramet + Gemcitabine
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 19: Slide 19
Slide 20: PET without activity in tumor deposits
PET w/o Activity in tumor deposits
Slide 21: After Samarium + Gemcitabine
After Samarium + Gemcitabine dose 5 After Samarium + Gemcitabine dose 8
Slide 22: After Samarium + Gemcitabine dose (of 8)
After Samarium + Gemcitabine dose 5 (of 8)
Slide 23: End of therapy
End of therapy 6 months after end of therapy
Slide 24: "RESIST using RECIST"
“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 (quantitativ
Slide 25: Repeated doses of Quadramet + Gemcitabine
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 26: Example: HDMTX, then Samarium + Gemcitabine
Example: HDMTX, then Samarium+ Gemcitabine 6/13/05 8/24/05
Slide 27: HDMTX, then Quadramet + gemcitabine
6/13/05 HDMTX, then Quadramet + gemcitabine - PET shows improvement in refractory osteosarcoma! 8/24/05
Slide 28: Excellent QOL s/p Quadramet + Gemcitabine
Excellent QOL s/p Quadramet+ Gemcitabine QOL [Picture of Female Patient]
Slide 29: Quadramet + Radiosensitizer
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 C
Slide 30: Quadramet in Osteosarcoma: Summary
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, g
Slide 31: MD Anderson Proton Therapy Center
MD Anderson Proton Therapy Center ($125 M Investment in Radiotherapy)
Slide 32: Questions?
Questions? Pete Anderson MD, PhD Direct line 713-563-0893 pmanders@mdanderson.org