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Chemotherapy-related toxicity in infants treated according to the Second National Wilms' Tumor Study
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Reducing chemotherapy doses for infants under 12 months in the National Wilms
Area of Science:
- Pediatric Oncology
- Clinical Trials
- Cancer Treatment
Background:
- The National Wil12 months of age have been included in the National Wilms' Tumor Study (NWTS) series of clinical trials.
- Early during the second NWTS, undue chemotherapy-related toxicity was encountered in infants under 12 months of age.
- This necessitated a reduction in the prescribed doses of actinomycin D (AMD), vincristine (VCR), and Adriamycin (ADR).
Purpose of the Study:
- To evaluate the impact of reduced chemotherapy doses on toxicity and therapeutic effectiveness in infants with Wilms' tumor.
- To determine if dose reduction in infants could achieve toxicity profiles similar to those in older children receiving full doses.
Main Methods:
- A retrospective analysis of infants under 12 months treated in the NWTS.
- Comparison of toxicity and outcomes between infants receiving full doses (FD) versus reduced doses (RD) of AMD, VCR, and ADR.
- Comparison of toxicity in infants receiving RD with that of older children receiving FD.
Main Results:
- Reduced doses (RD) significantly decreased severe hematologic toxic episodes (13% in RD vs. 47% in FD).
- Similar reductions in pulmonary and hepatic toxic effects were observed with RD.
- Treatment-related deaths decreased from 6% in the FD group to 0% in the RD group.
- Toxicity rates in infants receiving RD were comparable to those in older children receiving FD.
- Therapeutic effectiveness was not compromised by the dose reduction.
Conclusions:
- Reducing chemotherapy doses for infants under 12 months is a safe and effective strategy for Wilms' tumor treatment.
- Dose reduction significantly mitigates chemotherapy-related toxicity without compromising therapeutic outcomes.
- This approach allows for toxicity profiles in infants to align with those observed in older pediatric populations.
Abstract:
Babies under 12 months of age have been included in the National Wilms' Tumor Study (NWTS) series of clinical trials. Undue chemotherapy-related toxicity was encountered early during the course of the second NWTS. The prescribed doses of actinomycin D (AMD), vincristine (VCR), and Adriamycin ([ADR] doxorubicin; Adria Laboratories, Columbus, OH) were therefore halved. The frequency of severe hematologic toxic episodes was reduced (30 of 64 or 47% for babies receiving full doses [FD], and six of 48 or 13% for those given reduced doses [RD]). Similar reductions in pulmonary and hepatic effects were noted, and treatment-related deaths were reduced from 6% to 0 for the FD and RD samples, respectively. These frequencies among RD babies were similar to those encountered in 530 older children administered FD. Reduction of dose did not compromise therapeutic effectiveness.