Upfront window trial of topotecan in previously untreated children and adolescents with poor prognosis metastatic osteosarcoma: Children's Cancer Group (CCG) 7943 Journal Article
| Authors: | Seibel, N. L.; Krailo, M.; Chen, Z.; Healey, J.; Breitfeld, P. P.; Drachtman, R.; Greffe, B.; Nachman, J.; Nadel, H.; Sato, J. K.; Meyers, P. A.; Reaman, G. H. |
| Article Title: | Upfront window trial of topotecan in previously untreated children and adolescents with poor prognosis metastatic osteosarcoma: Children's Cancer Group (CCG) 7943 |
| Abstract: | BACKGROUND. Patients with metastatic osteosarcoma have a poor prognosis. The objectives of the study were to determine the antitumor activity and toxicity of topotecan (daily x5) in newly diagnosed patients with metastatic osteosarcoma followed by chemotherapy (ifosfamide, carboplatin, etoposide [ICE], alternating with cisplatin and doxorubicin [CD]). METHODS. Newly diagnosed patients (≤30 years of age) with extensive metastatic disease (primary and ≥5 pulmonary nodules and/or bone metastases) with normal hepatic, renal, and cardiac function were eligible. Patients were eligible to receive further topotecan after standard chemotherapy if they exhibited a response. Twenty-eight patients were enrolled. Seventeen had metastases to the lung only and 11 had metastases to the bone or multiple sites. Of 28 patients enrolled, 27 could be evaluated for response. A limited dose escalation was incorporated. RESULTS. No responses were seen in the 11 patients treated at 3 mg/m2/day. One partial response (PR) and 1 clinical response (CLR) were reported among 15 patients who received topotecan at 3.5 mg/m2/day. No dose-limiting toxicity was observed. Principal nondose-limiting toxicities were hematologic and gastrointestinal. The 2- and 5-year event-free survival rates were low, 7% and 4%, respectively, but the 2- and 5-year overall survival rates were 44% and 22%, respectively. CONCLUSIONS. Topotecan at dose of 3.5 mg/m2/day can be safely administered upfront to newly diagnosed patients without excessive toxicity. Insufficient activity was seen with topotecan in this schedule to warrant further studies in osteosarcoma. The combination of ICE and CD was tolerable when delivered after initial topotecan therapy. © 2007 American Cancer Society. |
| Keywords: | osteosarcoma; adolescent; adult; child; treatment outcome; treatment response; bone neoplasms; survival analysis; survival rate; clinical trial; drug tolerability; neutropenia; cisplatin; doxorubicin; dose response; drug safety; drug withdrawal; monotherapy; side effect; antineoplastic agents; bone metastasis; cancer patient; disease free survival; treatment; topotecan; carboplatin; infection; multiple cycle treatment; anemia; etoposide; nausea; thrombocytopenia; vomiting; antineoplastic combined chemotherapy protocols; lung neoplasms; weight reduction; creatinine; creatinine blood level; antineoplastic activity; continuous infusion; ifosfamide; childhood cancer; drug hypersensitivity; loading drug dose; alkaline phosphatase; bilirubin; lung metastasis; sepsis; alkaline phosphatase blood level; maximum tolerated dose; mesna; drug dose increase; bilirubin blood level; multiple organ failure; metastatic; lung nodule; septic shock; window |
| Journal Title: | Cancer |
| Volume: | 109 |
| Issue: | 8 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2007-04-15 |
| Start Page: | 1646 |
| End Page: | 1653 |
| Language: | English |
| DOI: | 10.1002/cncr.22553 |
| PUBMED: | 17334983 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 8" - "Export Date: 17 November 2011" - "CODEN: CANCA" - "Source: Scopus" |
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