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1دورية أكاديمية
المؤلفون: Palmerini, Emanuela, Meazza, Cristina, Tamburini, Angela, Bisogno, Gianni, Ferraresi, Virginia, Asaftei, Sebastian D, Milano, Giuseppe M, Coccoli, Luca, Manzitti, Carla, Luksch, Roberto, Serra, Massimo, Gambarotti, Marco, Donati, Davide M, Scotlandi, Katia, Bertulli, Rossella, Favre, Claudio, Longhi, Alessandra, Abate, Massimo E, Perrotta, Silverio, Mascarin, Maurizio, D'Angelo, Paolo, Cesari, Marilena, Staals, Eric L, Marchesi, Emanuela, Carretta, Elisa, Ibrahim, Toni, Casali, Paolo G, Picci, Piero, Fagioli, Franca, Ferrari, Stefano
المساهمون: E. Palmerini, C. Meazza, A. Tamburini, G. Bisogno, V. Ferraresi, S.D. Asaftei, G.M. Milano, L. Coccoli, C. Manzitti, R. Luksch, M. Serra, M. Gambarotti, D.M. Donati, K. Scotlandi, R. Bertulli, C. Favre, A. Longhi, M.E. Abate, S. Perrotta, M. Mascarin, P. D'Angelo, M. Cesari, E.L. Staal, E. Marchesi, E. Carretta, T. Ibrahim, P.G. Casali, P. Picci, F. Fagioli, S. Ferrari
مصطلحات موضوعية: ATP binding cassette subfamily B member 1 (ABCB1), P-glycoprotein, adolescents and young adults (AYAs), chemotherapy, high-grade bone sarcoma, mifamurtide, osteosarcoma, pediatric bone tumor, ATP Binding Cassette Transporter, Subfamily B, Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocol, Child, Disease-Free Survival, Extremitie, Human, Ifosfamide, Italy, Methotrexate, Prospective Studie, Retrospective Studie, Treatment Outcome, Young Adult, Bone Neoplasm, Settore MED/06 - Oncologia Medica
الوصف: Background According to retrospective osteosarcoma series, ABCB1/P-glycoprotein (Pgp) overexpression predicts for poor outcomes. A prospective trial to assess a risk-adapted treatment strategy using mifamurtide in Pgp+ patients was performed. Methods This was a phase 2, multicenter, uncontrolled trial including patients 40 years old or younger with nonmetastatic extremity high-grade osteosarcoma stratified according to Pgp expression. All patients received high-dose methotrexate, doxorubicin, and cisplatin (MAP) preoperatively. In Pgp+ patients, mifamurtide was added postoperatively and combined with MAP for a good histologic response (necrosis >= 90%; good responders [GRs]) or with high-dose ifosfamide (HDIFO) at 3 g/m(2)/d on days 1 to 5 for a histologic response < 90% (poor responders [PRs]). Pgp- patients received MAP postoperatively. After an amendment, the cumulative dose of methotrexate was increased from 60 to 120 g/m(2) (from 5 to 10 courses). The primary end point was event-free survival (EFS). A postamendment analysis was performed. Results In all, 279 patients were recruited, and 194 were included in the postamendment analysis: 70 (36%) were Pgp-, and 124 (64%) were Pgp+. The median follow-up was 51 months. For Pgp+ patients, 5-year EFS after definitive surgery (null hypothesis, 40%) was 69.8% (90% confidence interval [CI], 62.2%-76.2%): 59.8% in PRs and 83.7% in GRs. For Pgp- patients, the 5-year EFS rate was 66.4% (90% CI, 55.6%-75.1%). Conclusions This study showed that adjuvant mifamurtide, combined with HDIFO for a poor response to induction chemotherapy, could improve EFS in Pgp+ patients. Overall, the outcomes compared favorably with previous series. Mifamurtide and HDIFO as salvage chemotherapy are worth further study.
العلاقة: info:eu-repo/semantics/altIdentifier/pmid/35201621; info:eu-repo/semantics/altIdentifier/wos/WOS:000760375800001; volume:128; issue:10; firstpage:1958; lastpage:1966; numberofpages:9; journal:CANCER; https://hdl.handle.net/2434/945836Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85125149637
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2دورية أكاديمية
المؤلفون: Palmerini E., Meazza C., Tamburini A., Bisogno G., Ferraresi V., Asaftei S. D., Milano G. M., Coccoli L., Manzitti C., Luksch R., Serra M., Gambarotti M., Donati D. M., Scotlandi K., Bertulli R., Favre C., Longhi A., Abate M. E., Perrotta S., Mascarin M., D'Angelo P., Cesari M., Staals E. L., Marchesi E., Carretta E., Ibrahim T., Casali P. G., Picci P., Fagioli F., Ferrari S.
المساهمون: Palmerini, E., Meazza, C., Tamburini, A., Bisogno, G., Ferraresi, V., Asaftei, S. D., Milano, G. M., Coccoli, L., Manzitti, C., Luksch, R., Serra, M., Gambarotti, M., Donati, D. M., Scotlandi, K., Bertulli, R., Favre, C., Longhi, A., Abate, M. E., Perrotta, S., Mascarin, M., D'Angelo, P., Cesari, M., Staals, E. L., Marchesi, E., Carretta, E., Ibrahim, T., Casali, P. G., Picci, P., Fagioli, F., Ferrari, S.
مصطلحات موضوعية: adolescents and young adults (AYAs), ATP binding cassette subfamily B member 1 (ABCB1), chemotherapy, high-grade bone sarcoma, mifamurtide, osteosarcoma, P-glycoprotein, pediatric bone tumor, ATP Binding Cassette Transporter, Subfamily B, Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocol, Child, Disease-Free Survival, Extremitie, Human, Ifosfamide, Italy, Methotrexate, Prospective Studie, Retrospective Studie, Treatment Outcome, Young Adult, Bone Neoplasm
الوصف: Background: According to retrospective osteosarcoma series, ABCB1/P-glycoprotein (Pgp) overexpression predicts for poor outcomes. A prospective trial to assess a risk-adapted treatment strategy using mifamurtide in Pgp+ patients was performed. Methods: This was a phase 2, multicenter, uncontrolled trial including patients 40 years old or younger with nonmetastatic extremity high-grade osteosarcoma stratified according to Pgp expression. All patients received high-dose methotrexate, doxorubicin, and cisplatin (MAP) preoperatively. In Pgp+ patients, mifamurtide was added postoperatively and combined with MAP for a good histologic response (necrosis ≥ 90%; good responders [GRs]) or with high-dose ifosfamide (HDIFO) at 3 g/m2/d on days 1 to 5 for a histologic response < 90% (poor responders [PRs]). Pgp– patients received MAP postoperatively. After an amendment, the cumulative dose of methotrexate was increased from 60 to 120 g/m2 (from 5 to 10 courses). The primary end point was event-free survival (EFS). A postamendment analysis was performed. Results: In all, 279 patients were recruited, and 194 were included in the postamendment analysis: 70 (36%) were Pgp–, and 124 (64%) were Pgp+. The median follow-up was 51 months. For Pgp+ patients, 5-year EFS after definitive surgery (null hypothesis, 40%) was 69.8% (90% confidence interval [CI], 62.2%-76.2%): 59.8% in PRs and 83.7% in GRs. For Pgp– patients, the 5-year EFS rate was 66.4% (90% CI, 55.6%-75.1%). Conclusions: This study showed that adjuvant mifamurtide, combined with HDIFO for a poor response to induction chemotherapy, could improve EFS in Pgp+ patients. Overall, the outcomes compared favorably with previous series. Mifamurtide and HDIFO as salvage chemotherapy are worth further study.
العلاقة: info:eu-repo/semantics/altIdentifier/pmid/35201621; info:eu-repo/semantics/altIdentifier/wos/WOS:000760375800001; volume:128; issue:10; firstpage:1958; lastpage:1966; numberofpages:9; journal:CANCER; http://hdl.handle.net/11577/3448129Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85125149637
