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Topotecan in pediatric patients with recurrent and progressive solid tumors: a Pediatric Oncology Group phase II
R Nitschke1, J Parkhurst, J Sullivan
1Oklahoma University, Oklahoma City, USA.
Purpose:
A phase II study was designed to determine the efficacy of topotecan, an inhibitor of topoisomerase I, in the treatment of patients with progressive or recurrent pediatric extracranial solid tumors (STs).
Patients And Methods:
Patients younger than 21 years at the time of initial diagnosis with refractory STs were treated with 2 mg/m2 topotecan given by 30-minute infusions for 5 days repeated every 3 weeks. Granulocyte colony stimulating factor (G-CSF) was added to the regimen only after occurrence of severe neutropenia or therapy delay due to sustained neutropenia.
Results:
One hundred forty-one patients were treated with 539 courses of topotecan. Responses were seen in 34 patients (3 had complete responses [CRs], 2 had partial responses [PRs], and 24 had minor responses [MRs] or stable disease [SD]). The number of administered courses in patients with SD varied between 5 and 24, with a median of 10. The median time on the study for patients with SD was approximately 8.5 months. In patients without bone marrow involvement, the most frequent toxicity was myelosuppression: hemoglobin < 8 g/dl in 83 of 341 courses, absolute granulocyte count < 1,000/microl in 221 of 341 courses, and platelet count < 50,000/microl in 162 of 341 courses. Nausea and vomiting were infrequent; many patients were pretreated with ondansetron or granisetron. A recurrent rash developed in 16 patients and was usually well controlled with diphenhydramine and hydrocortisone. G-CSF was administered in 203 of 539 courses because of neutropenia. Therapy was delayed over 1 week in 33 instances.
Conclusion:
In previously treated patients, topotecan produced CRs and PRs in patients with neuroblastoma, Ewing's tumor, and retinoblastoma. In hepatoblastoma, rhabdomyosarcoma, and a few rare tumors, long-lasting MRs and SDs with excellent symptom control were seen. The toxicity of topotecan, predominantly myelosuppression, was tolerable.
Insights
Topotecan demonstrated efficacy in treating pediatric solid tumors, achieving complete and partial responses in neuroblastoma and Ewing's sarcoma. The drug’s toxicity, mainly myelosuppression, was manageable, offering a tolerable option for refractory pediatric cancers.
Area of Science:
- Pediatric Oncology
- Medical Oncology
- Pharmacology
Background:
- Topotecan, a topoisomerase I inhibitor, was evaluated in a Phase II clinical trial for pediatric patients with progressive or recurrent extracranial solid tumors (STs).
- The study aimed to assess the efficacy and toxicity of topotecan in this challenging patient population.
Observation:
- 141 pediatric patients with refractory STs received topotecan (2 mg/m2) intravenously for 5 days every 3 weeks.
- Granulocyte colony-stimulating factor (G-CSF) was administered selectively for neutropenia.
- Responses, including complete responses (CRs), partial responses (PRs), minor responses (MRs), and stable disease (SD), were observed in 34 patients.
Findings:
- Topotecan induced CRs and PRs in patients with neuroblastoma, Ewing's tumor, and retinoblastoma.
- Long-lasting MRs and SDs with effective symptom management were noted in hepatoblastoma and rhabdomyosarcoma.
- The primary toxicity was myelosuppression, which was generally tolerable. Nausea and vomiting were infrequent, and a rash occurred in some patients.
Implications:
- Topotecan represents a viable treatment option for previously treated pediatric patients with specific refractory solid tumors.
- The manageable toxicity profile suggests topotecan can be integrated into treatment regimens with careful monitoring.
- Further research may explore optimizing topotecan dosing or combination therapies for enhanced efficacy in pediatric STs.