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Addition of pamidronate to chemotherapy for treatment of osteosarcoma is feasible

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.

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Addition of pamidronate to chemotherapy for treatment of osteosarcoma is feasible

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  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

  2. Need for new agents in osteosarcoma • Population based data suggests little improvement in outcome in two decades • Addition of ifosfamide to cisplatin, doxorubicin and HDTMX did not improve survival

  3. Osteosarcoma 5-Year Survival Data <15 years 15-29 years % Surviving Surgery Only (Historical) 1975- 1981- 1987- 1993- 1980 1986 1992 2000 SEER

  4. 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 treatment. N Engl J Med. 1998;339:357-63.

  5. Bisphosphonates and osteosarcoma *synergy with chemotherapy

  6. Bisphosphonates and osteosarcoma *synergy with chemotherapy

  7. Choice of pamidronate

  8. Study Aims • 1. Determine safety and feasibility of concurrent pamidronate and chemo • 2. Estimate prosthesis survival for patients who receive pamidronate and chemotherapy • 3. Estimate EFS and survival for patients who receive pamidronate and chemotherapy

  9. Patient population • Newly diagnosed, untreated osteosarcoma • 29 patients with localized disease • 11 patients with metastasis at initial presentation

  10. Induction treatment regimen Pamidronate 2 mg/kg (max dose 90 mg) qmonth

  11. Maintenance treatment regimen Pamidronate 2 mg/kg (max dose 90 mg) qmonth

  12. 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

  13. Toxicity • Usual and expected toxicity with cisplatin, doxorubicin, HDMTX • No increase in nephrotoxicity or ototoxicity • No osteonecrosis of the jaw

  14. Orthopedic reconstruction • 21 endoprosthetic reconstructions • 13/14 uncemented implants osteointegrated • 12 allograft reconstructions • 2 failures, 4 delayed unions and 6 successful grafts • 5 of 33 reconstructions failed • No stress fractures, no growth disturbance • Results better than historical norm

  15. Conclusions • We can safely administer pamidronate and chemotherapy to young patients with osteosarcoma • EFS and survival are comparable to our historical institutional experience • Prosthesis survival is at least as good as our historical institutional experience

  16. Future Directions • Consider a prospective randomized trial of chemotherapy +/- bisphosphonate • Consider use of zoledronate rather than pamidronate • Zoledronate is more potent than pamidronate: increased risk for toxicity as well as increased potential for benefit • Will this require pilot data?

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