Influence of adriamycin dose in the outcome of patients with osteosarcoma treated with multidrug neoadjuvant chemotherapy

Results of two sequential studies

G. Bacci, P. Picci, S. Ferrari, R. Casadei, A. B. Del Prever, A. Tienghi, A. Mancini

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The results of two sequential studies of neoadjuvant chemotherapy for osteosarcoma of the extremities performed at Rizzoli Institute between 1986 and 1991 in 228 patients are presented. In both studies preoperative chemotherapy consisted of two cycles of high dose methotrexate (HDMTX), cisplatinum (CDP) and adriamycin (ADM). Postoperatively the good responder patients were treated with the same drugs used before surgery while in the poor responder patients ifosfamide was added to these three drugs. The preoperative treatment was the same in both studies while after surgery in the second protocol either the cumulative dose of ADM (270 mg/m2 instead of 360 mg/m2) or the single dose per cycle of this drug (60 mg/m2 instead of 90 mg/m2) was reduced. These changes in the last protocol were done to reduce the cardiotoxicity of ADM that was high in the first study (2 deaths and 1 heart transplantation). Since in the last protocol-in comparison with the first protocol-after surgery chemotherapy was restarted earlier and ADM was administered not as a single drug but in combination with the CDP the dose intensity of ADM was unchanged while the dose intensity of MTX, CDP and ifosfamide was higher than in the first study. The preliminary results of the 84 patients treated in the second study show a 2-year disease free survival significantly lower than that achieved in the 144 patients treated in the first study (37/51-73% vs 123/144-85%: P <0.008). In addition, even if in the last study there were no cases of clinical cardiotoxicity due to ADM, there was a significantly higher percentage of severe myelodepression that led to two deaths for infectious complications. These results suggest that in neoadjuvant treatment of osteosarcoma the total dose of ADM and/or the single dose per cycle of the same drug are an important determinant of outcome and that increasing the dose-intensity of less toxic but less active agents, MTX, CDP and ifosfamide, at the expense of the more active and more toxic agent, ADM, can lead to a poorer outcome without reducing toxicity.

Original languageEnglish
Pages (from-to)237-246
Number of pages10
JournalJournal of Chemotherapy
Volume5
Issue number4
Publication statusPublished - 1993

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Osteosarcoma
Doxorubicin
Cytidine Diphosphate
Drug Therapy
Ifosfamide
Poisons
Pharmaceutical Preparations
Neoadjuvant Therapy
Drug Combinations
Heart Transplantation
Methotrexate
Disease-Free Survival
Extremities

ASJC Scopus subject areas

  • Microbiology (medical)
  • Pharmacology (medical)

Cite this

Bacci, G., Picci, P., Ferrari, S., Casadei, R., Del Prever, A. B., Tienghi, A., & Mancini, A. (1993). Influence of adriamycin dose in the outcome of patients with osteosarcoma treated with multidrug neoadjuvant chemotherapy: Results of two sequential studies. Journal of Chemotherapy, 5(4), 237-246.

Influence of adriamycin dose in the outcome of patients with osteosarcoma treated with multidrug neoadjuvant chemotherapy : Results of two sequential studies. / Bacci, G.; Picci, P.; Ferrari, S.; Casadei, R.; Del Prever, A. B.; Tienghi, A.; Mancini, A.

In: Journal of Chemotherapy, Vol. 5, No. 4, 1993, p. 237-246.

Research output: Contribution to journalArticle

Bacci, G, Picci, P, Ferrari, S, Casadei, R, Del Prever, AB, Tienghi, A & Mancini, A 1993, 'Influence of adriamycin dose in the outcome of patients with osteosarcoma treated with multidrug neoadjuvant chemotherapy: Results of two sequential studies', Journal of Chemotherapy, vol. 5, no. 4, pp. 237-246.
Bacci, G. ; Picci, P. ; Ferrari, S. ; Casadei, R. ; Del Prever, A. B. ; Tienghi, A. ; Mancini, A. / Influence of adriamycin dose in the outcome of patients with osteosarcoma treated with multidrug neoadjuvant chemotherapy : Results of two sequential studies. In: Journal of Chemotherapy. 1993 ; Vol. 5, No. 4. pp. 237-246.
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abstract = "The results of two sequential studies of neoadjuvant chemotherapy for osteosarcoma of the extremities performed at Rizzoli Institute between 1986 and 1991 in 228 patients are presented. In both studies preoperative chemotherapy consisted of two cycles of high dose methotrexate (HDMTX), cisplatinum (CDP) and adriamycin (ADM). Postoperatively the good responder patients were treated with the same drugs used before surgery while in the poor responder patients ifosfamide was added to these three drugs. The preoperative treatment was the same in both studies while after surgery in the second protocol either the cumulative dose of ADM (270 mg/m2 instead of 360 mg/m2) or the single dose per cycle of this drug (60 mg/m2 instead of 90 mg/m2) was reduced. These changes in the last protocol were done to reduce the cardiotoxicity of ADM that was high in the first study (2 deaths and 1 heart transplantation). Since in the last protocol-in comparison with the first protocol-after surgery chemotherapy was restarted earlier and ADM was administered not as a single drug but in combination with the CDP the dose intensity of ADM was unchanged while the dose intensity of MTX, CDP and ifosfamide was higher than in the first study. The preliminary results of the 84 patients treated in the second study show a 2-year disease free survival significantly lower than that achieved in the 144 patients treated in the first study (37/51-73{\%} vs 123/144-85{\%}: P <0.008). In addition, even if in the last study there were no cases of clinical cardiotoxicity due to ADM, there was a significantly higher percentage of severe myelodepression that led to two deaths for infectious complications. These results suggest that in neoadjuvant treatment of osteosarcoma the total dose of ADM and/or the single dose per cycle of the same drug are an important determinant of outcome and that increasing the dose-intensity of less toxic but less active agents, MTX, CDP and ifosfamide, at the expense of the more active and more toxic agent, ADM, can lead to a poorer outcome without reducing toxicity.",
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