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Multicenter Analysis of Genomically Targeted Single Patient Use Requests for Pediatric Neoplasms
Himalee S Sabnis1,2, David S Shulman3, Benjamin Mizukawa4,5
1Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA.
Purpose:
The US Food and Drug Administration-expanded access program (EAP) uses a single patient use (SPU) mechanism to provide patient access to investigational agents in situations where no satisfactory or comparable therapy is available. Genomic profiling of de novo and relapsed or refractory childhood cancer has led to increased identification of new drug targets in the last decade. The aim of this study is to examine the SPU experience for genomically targeted therapies in patients with pediatric cancer.
Patients And Methods:
All genomically targeted therapeutic SPUs obtained over a 5-year period were evaluated at four large pediatric cancer programs. Data were collected on the type of neoplasm, agents requested, corresponding molecularly informed targets, and clinical outcomes.
Results:
A total of 45 SPUs in 44 patients were identified. Requests were predominantly made for CNS and solid tumors (84.4%) compared with hematologic malignancies (15.6%). Lack of an available clinical trial was the main reason for SPU initiation (64.4%). The median time from US Food and Drug Administration submission to approval was 3 days (range, 0-12 days) and from Institutional Review Board submission to approval was 5 days (range, 0-50 days). Objective tumor response was seen in 39.5% (15 of 38) of all evaluable SPUs. Disease progression was the primary reason for discontinuation of drug (66.7%) followed by toxicity (13.3%).
Conclusion:
SPU requests remain an important mechanism for pediatric access to genomically targeted agents given the limited availability of targeted clinical trials for children with high-risk neoplasms. Furthermore, this subset of SPUs resulted in a substantial number of objective tumor responses. The development of a multi-institutional data registry of SPUs may enable systematic review of toxicity and clinical outcomes and provide evidence-based access to new drugs in rare pediatric cancers.
Insights
Single patient use (SPU) provides pediatric cancer patients access to targeted therapies when clinical trials are unavailable. This important access mechanism resulted in objective tumor responses, highlighting its value for rare pediatric cancers.
Area of Science:
- Oncology
- Genomics
- Pediatric Medicine
Background:
- The US Food and Drug Administration's expanded access program (EAP) utilizes single patient use (SPU) to provide investigational agents for patients lacking satisfactory therapies.
- Genomic profiling has identified new drug targets for pediatric cancers, increasing the need for targeted treatment access.
Purpose of the Study:
- To examine the single patient use (SPU) experience for genomically targeted therapies in pediatric cancer patients.
- To assess the efficacy and utilization of SPU for accessing novel molecularly informed treatments.
Main Methods:
- A retrospective evaluation of all genomically targeted therapeutic SPUs over a 5-year period at four major pediatric cancer centers.
- Data collection included tumor type, requested agents, molecular targets, and clinical outcomes.
Main Results:
- 45 SPUs in 44 patients were identified, predominantly for CNS and solid tumors (84.4%).
- Lack of clinical trials was the primary driver for SPU initiation (64.4%).
- Objective tumor responses were observed in 39.5% of evaluable SPUs, with disease progression being the main reason for discontinuation.
Conclusions:
- SPU is a crucial pathway for pediatric access to genomically targeted agents, especially when targeted clinical trials are limited for high-risk pediatric neoplasms.
- This SPU subset demonstrated significant objective tumor responses, underscoring its clinical utility.
- Establishing a multi-institutional SPU registry could facilitate systematic reviews of outcomes and evidence-based access to novel drugs for rare pediatric cancers.
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