Carboplatin/ifosfamide window therapy for osteosarcoma: Results of the St Jude Children's Research Hospital OS-91 trial

W. H. Meyer, C. B. Pratt, C. A. Poquette, B. N. Rao, D. M. Parham, N. M. Marina, A. S. Pappo, H. H. Mahmoud, J. J. Jenkins, J. Harper, M. Neel, B. D. Fletcher

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Purpose: To determine the activity of carboplatin/ifosfamide in patients with previously untreated osteosarcoma and to estimate patient outcomes after a multiagent chemotherapy protocol that eliminated cisplatin. Patients and Methods: Sixty-nine patients with newly diagnosed, previously untreated osteosarcoma received three cycles of carboplatin (560 mg/m2 × 1) and ifosfamide (2.65 g/m2/d × 3). Assessment of response was evaluated after two (week 6) and three (week 9) chemotherapy cycles. At week 9, histologic response was assessed. Adjuvant therapy comprised two additional carboplatin/ifosfamide cycles, doxorubicin, and high-dose methotrexate. Patients were stratified at enrollment: stratum A, resectable primary tumor without metastases; stratum B, unresectable primary tumor; and stratum C, metastatic disease at diagnosis. Week 6 response was compared with that of a historic group that received only ifosfamide during the initial window evaluation. Results: The clinical and radiographic response rate to three cycles of carboplatin/ifosfamide was 67.7% (95% confidence interval, 55.0% to 78.8%). Compared with the historic population who received only ifosfamide, the combination of carboplatin and ifosfamide reduced the progressive disease rate at week 6 (31.9% v 9%, P = .003). For patients in stratum A, the 3-year event-free survival and survival were 72.3% ± 6.7% and 76.4% ± 6.4%, respectively. Patients who received carboplatin-based therapy had less long-term renal toxicity and ototoxicity. Conclusion: This pilot trial suggests that carboplatin/ifosfamide combination chemotherapy has substantia] antitumor activity. In the context of a multiagent chemotherapy protocol comprising high-dose methotrexate and doxorubicin, we found that the addition of carboplatin/ifosfamide resulted in patient outcomes comparable to trials using cisplatin-based therapy with less long-term toxicity.

Original languageEnglish (US)
Pages (from-to)171-182
Number of pages12
JournalJournal of Clinical Oncology
Volume19
Issue number1
DOIs
StatePublished - Jan 1 2001

Fingerprint

Ifosfamide
Carboplatin
Osteosarcoma
Research
Therapeutics
Methotrexate
Drug Therapy
Doxorubicin
Cisplatin
Combination Drug Therapy
Disease-Free Survival
Neoplasms
Confidence Intervals
Neoplasm Metastasis
Kidney
Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Meyer, W. H., Pratt, C. B., Poquette, C. A., Rao, B. N., Parham, D. M., Marina, N. M., ... Fletcher, B. D. (2001). Carboplatin/ifosfamide window therapy for osteosarcoma: Results of the St Jude Children's Research Hospital OS-91 trial. Journal of Clinical Oncology, 19(1), 171-182. https://doi.org/10.1200/JCO.2001.19.1.171

Carboplatin/ifosfamide window therapy for osteosarcoma : Results of the St Jude Children's Research Hospital OS-91 trial. / Meyer, W. H.; Pratt, C. B.; Poquette, C. A.; Rao, B. N.; Parham, D. M.; Marina, N. M.; Pappo, A. S.; Mahmoud, H. H.; Jenkins, J. J.; Harper, J.; Neel, M.; Fletcher, B. D.

In: Journal of Clinical Oncology, Vol. 19, No. 1, 01.01.2001, p. 171-182.

Research output: Contribution to journalArticle

Meyer, WH, Pratt, CB, Poquette, CA, Rao, BN, Parham, DM, Marina, NM, Pappo, AS, Mahmoud, HH, Jenkins, JJ, Harper, J, Neel, M & Fletcher, BD 2001, 'Carboplatin/ifosfamide window therapy for osteosarcoma: Results of the St Jude Children's Research Hospital OS-91 trial', Journal of Clinical Oncology, vol. 19, no. 1, pp. 171-182. https://doi.org/10.1200/JCO.2001.19.1.171
Meyer, W. H. ; Pratt, C. B. ; Poquette, C. A. ; Rao, B. N. ; Parham, D. M. ; Marina, N. M. ; Pappo, A. S. ; Mahmoud, H. H. ; Jenkins, J. J. ; Harper, J. ; Neel, M. ; Fletcher, B. D. / Carboplatin/ifosfamide window therapy for osteosarcoma : Results of the St Jude Children's Research Hospital OS-91 trial. In: Journal of Clinical Oncology. 2001 ; Vol. 19, No. 1. pp. 171-182.
@article{1104ec870d894fb0abef81e0eebbbe98,
title = "Carboplatin/ifosfamide window therapy for osteosarcoma: Results of the St Jude Children's Research Hospital OS-91 trial",
abstract = "Purpose: To determine the activity of carboplatin/ifosfamide in patients with previously untreated osteosarcoma and to estimate patient outcomes after a multiagent chemotherapy protocol that eliminated cisplatin. Patients and Methods: Sixty-nine patients with newly diagnosed, previously untreated osteosarcoma received three cycles of carboplatin (560 mg/m2 × 1) and ifosfamide (2.65 g/m2/d × 3). Assessment of response was evaluated after two (week 6) and three (week 9) chemotherapy cycles. At week 9, histologic response was assessed. Adjuvant therapy comprised two additional carboplatin/ifosfamide cycles, doxorubicin, and high-dose methotrexate. Patients were stratified at enrollment: stratum A, resectable primary tumor without metastases; stratum B, unresectable primary tumor; and stratum C, metastatic disease at diagnosis. Week 6 response was compared with that of a historic group that received only ifosfamide during the initial window evaluation. Results: The clinical and radiographic response rate to three cycles of carboplatin/ifosfamide was 67.7{\%} (95{\%} confidence interval, 55.0{\%} to 78.8{\%}). Compared with the historic population who received only ifosfamide, the combination of carboplatin and ifosfamide reduced the progressive disease rate at week 6 (31.9{\%} v 9{\%}, P = .003). For patients in stratum A, the 3-year event-free survival and survival were 72.3{\%} ± 6.7{\%} and 76.4{\%} ± 6.4{\%}, respectively. Patients who received carboplatin-based therapy had less long-term renal toxicity and ototoxicity. Conclusion: This pilot trial suggests that carboplatin/ifosfamide combination chemotherapy has substantia] antitumor activity. In the context of a multiagent chemotherapy protocol comprising high-dose methotrexate and doxorubicin, we found that the addition of carboplatin/ifosfamide resulted in patient outcomes comparable to trials using cisplatin-based therapy with less long-term toxicity.",
author = "Meyer, {W. H.} and Pratt, {C. B.} and Poquette, {C. A.} and Rao, {B. N.} and Parham, {D. M.} and Marina, {N. M.} and Pappo, {A. S.} and Mahmoud, {H. H.} and Jenkins, {J. J.} and J. Harper and M. Neel and Fletcher, {B. D.}",
year = "2001",
month = "1",
day = "1",
doi = "10.1200/JCO.2001.19.1.171",
language = "English (US)",
volume = "19",
pages = "171--182",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "1",

}

TY - JOUR

T1 - Carboplatin/ifosfamide window therapy for osteosarcoma

T2 - Results of the St Jude Children's Research Hospital OS-91 trial

AU - Meyer, W. H.

AU - Pratt, C. B.

AU - Poquette, C. A.

AU - Rao, B. N.

AU - Parham, D. M.

AU - Marina, N. M.

AU - Pappo, A. S.

AU - Mahmoud, H. H.

AU - Jenkins, J. J.

AU - Harper, J.

AU - Neel, M.

AU - Fletcher, B. D.

PY - 2001/1/1

Y1 - 2001/1/1

N2 - Purpose: To determine the activity of carboplatin/ifosfamide in patients with previously untreated osteosarcoma and to estimate patient outcomes after a multiagent chemotherapy protocol that eliminated cisplatin. Patients and Methods: Sixty-nine patients with newly diagnosed, previously untreated osteosarcoma received three cycles of carboplatin (560 mg/m2 × 1) and ifosfamide (2.65 g/m2/d × 3). Assessment of response was evaluated after two (week 6) and three (week 9) chemotherapy cycles. At week 9, histologic response was assessed. Adjuvant therapy comprised two additional carboplatin/ifosfamide cycles, doxorubicin, and high-dose methotrexate. Patients were stratified at enrollment: stratum A, resectable primary tumor without metastases; stratum B, unresectable primary tumor; and stratum C, metastatic disease at diagnosis. Week 6 response was compared with that of a historic group that received only ifosfamide during the initial window evaluation. Results: The clinical and radiographic response rate to three cycles of carboplatin/ifosfamide was 67.7% (95% confidence interval, 55.0% to 78.8%). Compared with the historic population who received only ifosfamide, the combination of carboplatin and ifosfamide reduced the progressive disease rate at week 6 (31.9% v 9%, P = .003). For patients in stratum A, the 3-year event-free survival and survival were 72.3% ± 6.7% and 76.4% ± 6.4%, respectively. Patients who received carboplatin-based therapy had less long-term renal toxicity and ototoxicity. Conclusion: This pilot trial suggests that carboplatin/ifosfamide combination chemotherapy has substantia] antitumor activity. In the context of a multiagent chemotherapy protocol comprising high-dose methotrexate and doxorubicin, we found that the addition of carboplatin/ifosfamide resulted in patient outcomes comparable to trials using cisplatin-based therapy with less long-term toxicity.

AB - Purpose: To determine the activity of carboplatin/ifosfamide in patients with previously untreated osteosarcoma and to estimate patient outcomes after a multiagent chemotherapy protocol that eliminated cisplatin. Patients and Methods: Sixty-nine patients with newly diagnosed, previously untreated osteosarcoma received three cycles of carboplatin (560 mg/m2 × 1) and ifosfamide (2.65 g/m2/d × 3). Assessment of response was evaluated after two (week 6) and three (week 9) chemotherapy cycles. At week 9, histologic response was assessed. Adjuvant therapy comprised two additional carboplatin/ifosfamide cycles, doxorubicin, and high-dose methotrexate. Patients were stratified at enrollment: stratum A, resectable primary tumor without metastases; stratum B, unresectable primary tumor; and stratum C, metastatic disease at diagnosis. Week 6 response was compared with that of a historic group that received only ifosfamide during the initial window evaluation. Results: The clinical and radiographic response rate to three cycles of carboplatin/ifosfamide was 67.7% (95% confidence interval, 55.0% to 78.8%). Compared with the historic population who received only ifosfamide, the combination of carboplatin and ifosfamide reduced the progressive disease rate at week 6 (31.9% v 9%, P = .003). For patients in stratum A, the 3-year event-free survival and survival were 72.3% ± 6.7% and 76.4% ± 6.4%, respectively. Patients who received carboplatin-based therapy had less long-term renal toxicity and ototoxicity. Conclusion: This pilot trial suggests that carboplatin/ifosfamide combination chemotherapy has substantia] antitumor activity. In the context of a multiagent chemotherapy protocol comprising high-dose methotrexate and doxorubicin, we found that the addition of carboplatin/ifosfamide resulted in patient outcomes comparable to trials using cisplatin-based therapy with less long-term toxicity.

UR - http://www.scopus.com/inward/record.url?scp=0035148019&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035148019&partnerID=8YFLogxK

U2 - 10.1200/JCO.2001.19.1.171

DO - 10.1200/JCO.2001.19.1.171

M3 - Article

C2 - 11134210

AN - SCOPUS:0035148019

VL - 19

SP - 171

EP - 182

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 1

ER -