Addition of pamidronate to chemotherapy for treatment of .ppt

1、Addition of pamidronate to chemotherapy for treatment of osteosarcoma is feasible,Meyers PA, Healey JH, Athanasian E, Boland P, Morris C, Laquaglia MP, Antonescu C, Wexler L, Merchant M, Merola P, Chou A, Abramson S, Kellick M Memorial Sloan-Kettering Cancer Center,Need for new agents in osteosarcom

2、a,Population based data suggests little improvement in outcome in two decadesAddition of ifosfamide to cisplatin, doxorubicin and HDTMX did not improve survival,Osteosarcoma 5-Year Survival Data,Surgery Only (Historical),1975-,1980,1981-,1986,1987-,1992,% Surviving,1993-,2000,SEER,15 years 15-29 yea

3、rs,Bisphosphonates and breast cancer,Clodronate reduced the risk of bone metastases But also Reduced the risk of visceral metastases,Diel IJ, Solomayer EF, Costa SD, Gollan C, Goerner R, Wallwiener D, Kaufmann M, Bastert G. Reduction in new metastases in breast cancer with adjuvant clodronate treatm

4、ent. N Engl J Med. 1998;339:357-63.,Bisphosphonates and osteosarcoma,*synergy with chemotherapy,Bisphosphonates and osteosarcoma,*synergy with chemotherapy,Choice of pamidronate,Study Aims,1. Determine safety and feasibility of concurrent pamidronate and chemo 2. Estimate prosthesis survival for pat

5、ients who receive pamidronate and chemotherapy 3. Estimate EFS and survival for patients who receive pamidronate and chemotherapy,Patient population,Newly diagnosed, untreated osteosarcoma 29 patients with localized disease 11 patients with metastasis at initial presentation,Induction treatment regi

6、men,Pamidronate 2 mg/kg (max dose 90 mg) qmonth,Maintenance treatment regimen,Pamidronate 2 mg/kg (max dose 90 mg) qmonth,Pamidronate dose schedule,Pamidronate 2 mg/kg (max dose 90 mg) qmonth for one year (12 doses) Separate pamidronate from cisplatin or HDMTX by at least 48 hours,Toxicity,Usual and

7、 expected toxicity with cisplatin, doxorubicin, HDMTX No increase in nephrotoxicity or ototoxicity No osteonecrosis of the jaw,Orthopedic reconstruction,21 endoprosthetic reconstructions13/14 uncemented implants osteointegrated 12 allograft reconstructions2 failures, 4 delayed unions and 6 successfu

8、l grafts 5 of 33 reconstructions failed No stress fractures, no growth disturbance Results better than historical norm,Conclusions,We can safely administer pamidronate and chemotherapy to young patients with osteosarcoma EFS and survival are comparable to our historical institutional experience Pros

9、thesis survival is at least as good as our historical institutional experience,Future Directions,Consider a prospective randomized trial of chemotherapy +/- bisphosphonateConsider use of zoledronate rather than pamidronateZoledronate is more potent than pamidronate: increased risk for toxicity as well as increased potential for benefit Will this require pilot data?,