Response of Children with Stage IV Soft Tissue Sarcoma to Topotecan and Carboplatin: A Phase II Window Trial of the Cooperative Soft Tissue Sarcoma Group

 

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Abstract

Purpose:

To investigate antitumor activity and toxicity associated with combined topotecan and carboplatin treatment in children and adolescents with metastasized, untreated soft tissue sarcoma (STS).

Patients and Methods:

Patients (n=34) less than 21 years old and untreated, stage IV STS. Patients were treated with topotecan (1 mg/m²/d for 4 days) and carboplatin (150 mg/m²/d for 4 days) (TC course) during week 1 and 4 of a chemotherapy window trial, which was followed by chemotherapy and local therapy from week 6 on. We evaluated the side effects, toxicity and tumor response (using RECIST criteria) 6 weeks after starting the 2 TC chemotherapy courses.

Results:

The objective response rate (ORR) was 38% (n=13 patients with a partial response (PR)), and a stable disease (SD) was reached in 11 cases. No patient showed a complete response (CR) of all metastatic lesions, although 1 patient showed a CR of the target lesion. 2 patients died of progress of disease (PD). Toxicity was mainly hematological (grade III/IV toxicity 79%), and nonhematological toxicities mainly included infection, fever, nausea,and vomiting. Regarding adverse events, 4 probable and 8 possible events related to study medication occurred among the 66 courses of TC.

Conclusion:

In conclusion, TC was potent against high-risk STS, but results and toxicity data were not superior to former published monotherapeutic topotecan therapies.

Zusammenfassung

Hintergrund:

Untersuchung zur Polychemotherapie mit Topotecan und Carboplatin bei Kindern und Jungendlichen mit metastasierten, nicht vorbehandelten Weichteilsarkomen be­­züglich Ansprechens und Toxizität.

Patienten und Methode:

Untersucht wurden 34 Patienten unter 21 Jahren mit nicht-vorbehandelten Stadium-IV-Weichteilsarkomen. Die Patienten wurden in einer Window-Studie mit Topotecan (1 mg/m²/d an 4 Tagen) und Carboplatin (150 mg/m²/d an 4 Tagen) in Woche 1 und 4 behandelt. In Woche 6 erfolgte eine Evaluation des Ansprechens nach RECIST-Kriterien, der To­­xizität und der Nebenwirkungen.

Ergebnisse:

Das Ansprechen (objective response rate, ORR) betrug 38% ( n=13 Patienten mit partiellem Ansprechen (PR)), ein Stable disease (SD) konn­te in 11 Fällen beobachtet werden. Kein Patient zeigte ein komplettes Ansprechen aller Metastasen, bei einer Patientin konnte der Primärtumor nicht mehr nachgewiesen werden. Zwei Patienten zeigten einen Progress. Die Toxi­zität beschränkte sich weitgehend auf hämatologische Toxizität, nicht-hämatologische Probleme waren Infektionen, Fieber, Übelkeit und Erbrechen. Die Ergebnisse der Studie waren vergleichbar mit denen aus Studien mit einer Topotecan-Monotherapie.

Schlussfolgerung:

Die TC-Window-Chemotherapie zeigte sich nach 6 Wochen als wirksam gegen Hochrisikosarkome, war jedoch früheren Monotherapiestudien auch in Bezug auf die Toxi­zität nicht überlegen. Langszeitdaten stehen aus.

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