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Neoadjuvant chemotherapy with methotrexate, cisplatin, and doxorubicin with or without ifosfamide in nonmetastatic osteosarcoma of the extremity: an Italian sarcoma group trial ISG/OS-1.
J Clin Oncol. 2012 Jun 10; 30(17):2112-8.JC

Abstract

PURPOSE

We compared two chemotherapy regimens that included methotrexate (MTX), cisplatin (CDP), and doxorubicin (ADM) with or without ifosfamide (IFO) in patients with nonmetastatic osteosarcoma of the extremity.

PATIENTS AND METHODS

Patients age ≤ 40 years randomly received regimens with the same cumulative doses of drugs (ADM 420 mg/m(2), MTX 120 g/m(2), CDP 600 mg/m(2), and IFO 30 g/m(2)) but with different durations (arm A, 44 weeks; arm B, 34 weeks). IFO was given postoperatively when pathologic response to MTX-CDP-ADM was poor (arm A) or given in the primary phase of chemotherapy with MTX-CDP-ADM (arm B). End points of the study included pathologic response to preoperative chemotherapy, toxicity, and survival. Given the feasibility of accrual, the statistical plan only permitted detection of a 15% difference in 5-year overall survival (OS).

RESULTS

From April 2001 to December 2006, 246 patients were enrolled. Two hundred thirty patients (94%) underwent limb salvage surgery (arm A, 92%; arm B, 96%; P = .5). Chemotherapy-induced necrosis was good in 45% of patients (48% in arm A, 42% in arm B; P = .3). Four patients died of treatment-related toxicity (arm A, n = 1; arm B, n = 3). A significantly higher incidence of hematologic toxicity was reported in arm B. With a median follow-up of 66 months (range, 1 to 104 months), 5-year OS and event-free survival (EFS) rates were not significantly different between arm A and arm B, with OS being 73% (95% CI, 65% to 81%) in arm A and 74% (95% CI, 66% to 82%) in arm B and EFS being 64% (95% CI, 56% to 73%) in arm A and 55% (95% CI, 46% to 64%) in arm B.

CONCLUSION

IFO added to MTX, CDP, and ADM from the preoperative phase does not improve the good responder rate and increases hematologic toxicity. IFO should only be considered in patients who have a poor histologic response to MTX, CDP, and ADM.

Authors+Show Affiliations

Istituto Ortopedico Rizzoli, Bologna, Italy. stefano.ferrari@ior.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22564997

Citation

Ferrari, Stefano, et al. "Neoadjuvant Chemotherapy With Methotrexate, Cisplatin, and Doxorubicin With or Without Ifosfamide in Nonmetastatic Osteosarcoma of the Extremity: an Italian Sarcoma Group Trial ISG/OS-1." Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, vol. 30, no. 17, 2012, pp. 2112-8.
Ferrari S, Ruggieri P, Cefalo G, et al. Neoadjuvant chemotherapy with methotrexate, cisplatin, and doxorubicin with or without ifosfamide in nonmetastatic osteosarcoma of the extremity: an Italian sarcoma group trial ISG/OS-1. J Clin Oncol. 2012;30(17):2112-8.
Ferrari, S., Ruggieri, P., Cefalo, G., Tamburini, A., Capanna, R., Fagioli, F., Comandone, A., Bertulli, R., Bisogno, G., Palmerini, E., Alberghini, M., Parafioriti, A., Linari, A., Picci, P., & Bacci, G. (2012). Neoadjuvant chemotherapy with methotrexate, cisplatin, and doxorubicin with or without ifosfamide in nonmetastatic osteosarcoma of the extremity: an Italian sarcoma group trial ISG/OS-1. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 30(17), 2112-8. https://doi.org/10.1200/JCO.2011.38.4420
Ferrari S, et al. Neoadjuvant Chemotherapy With Methotrexate, Cisplatin, and Doxorubicin With or Without Ifosfamide in Nonmetastatic Osteosarcoma of the Extremity: an Italian Sarcoma Group Trial ISG/OS-1. J Clin Oncol. 2012 Jun 10;30(17):2112-8. PubMed PMID: 22564997.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neoadjuvant chemotherapy with methotrexate, cisplatin, and doxorubicin with or without ifosfamide in nonmetastatic osteosarcoma of the extremity: an Italian sarcoma group trial ISG/OS-1. AU - Ferrari,Stefano, AU - Ruggieri,Pietro, AU - Cefalo,Graziella, AU - Tamburini,Angela, AU - Capanna,Rodolfo, AU - Fagioli,Franca, AU - Comandone,Alessandro, AU - Bertulli,Rossella, AU - Bisogno,Gianni, AU - Palmerini,Emanuela, AU - Alberghini,Marco, AU - Parafioriti,Antonina, AU - Linari,Alessandra, AU - Picci,Piero, AU - Bacci,Gaetano, Y1 - 2012/05/07/ PY - 2012/5/9/entrez PY - 2012/5/9/pubmed PY - 2012/8/24/medline SP - 2112 EP - 8 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JO - J. Clin. Oncol. VL - 30 IS - 17 N2 - PURPOSE: We compared two chemotherapy regimens that included methotrexate (MTX), cisplatin (CDP), and doxorubicin (ADM) with or without ifosfamide (IFO) in patients with nonmetastatic osteosarcoma of the extremity. PATIENTS AND METHODS: Patients age ≤ 40 years randomly received regimens with the same cumulative doses of drugs (ADM 420 mg/m(2), MTX 120 g/m(2), CDP 600 mg/m(2), and IFO 30 g/m(2)) but with different durations (arm A, 44 weeks; arm B, 34 weeks). IFO was given postoperatively when pathologic response to MTX-CDP-ADM was poor (arm A) or given in the primary phase of chemotherapy with MTX-CDP-ADM (arm B). End points of the study included pathologic response to preoperative chemotherapy, toxicity, and survival. Given the feasibility of accrual, the statistical plan only permitted detection of a 15% difference in 5-year overall survival (OS). RESULTS: From April 2001 to December 2006, 246 patients were enrolled. Two hundred thirty patients (94%) underwent limb salvage surgery (arm A, 92%; arm B, 96%; P = .5). Chemotherapy-induced necrosis was good in 45% of patients (48% in arm A, 42% in arm B; P = .3). Four patients died of treatment-related toxicity (arm A, n = 1; arm B, n = 3). A significantly higher incidence of hematologic toxicity was reported in arm B. With a median follow-up of 66 months (range, 1 to 104 months), 5-year OS and event-free survival (EFS) rates were not significantly different between arm A and arm B, with OS being 73% (95% CI, 65% to 81%) in arm A and 74% (95% CI, 66% to 82%) in arm B and EFS being 64% (95% CI, 56% to 73%) in arm A and 55% (95% CI, 46% to 64%) in arm B. CONCLUSION: IFO added to MTX, CDP, and ADM from the preoperative phase does not improve the good responder rate and increases hematologic toxicity. IFO should only be considered in patients who have a poor histologic response to MTX, CDP, and ADM. SN - 1527-7755 UR - https://www.unboundmedicine.com/medline/citation/22564997/Neoadjuvant_chemotherapy_with_methotrexate_cisplatin_and_doxorubicin_with_or_without_ifosfamide_in_nonmetastatic_osteosarcoma_of_the_extremity:_an_Italian_sarcoma_group_trial_ISG/OS_1_ L2 - http://ascopubs.org/doi/full/10.1200/JCO.2011.38.4420?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -