Clinical characteristics and outcomes of pediatric oncology patients with aggressive biology enrolled in phase I clinical trials designed for adults: the university of Texas MD anderson cancer center experience.

Fernando F Corrales-Medina,Eugenie S Kleinerman,Pete Anderson,Aung Naing,Sarina Piha Paul,Apostolia M Tsimberidou,David S Hong,Winston W Huh,Gerald Falchook,Daniela Egas-Bejar,Kenneth Hess,Filip Janku,Razelle Kurzrock,Vivek Subbiah,Jennifer Wheler,Cesar Nunez,Cynthia Herzog

doi:10.18632/oncoscience.68

Fernando F Corrales-Medina, Eugenie S Kleinerman + Show 15 more

Open Access

https://doi.org/10.18632/oncoscience.68

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Abstract

Children (patients ≤ 18 years of age) are not usually included on pharmaceutical industry sponsored Phase I trials. We reviewed the medical records of 40 patients ≤ 18 years treated in ≥ 1 phase I trial at MD Anderson. The median OS was 8.5 months (95% CI, 5.5-13.2 months). In the multivariate analysis, age ≥15 only predicted increased OS (P = 0.0065), and >3 prior therapies (P = 0.053) predicted decreased OS. The median PFS was 2.8 months (95% CI, 2.3-4.1 months). In the multivariate analysis, independent factors that predicted increased PFS were age ≥15 years (P < 0.001) and prior radiation therapy (P = 0.049); performance status >1 (P < 0.001) and >3 prior therapies (P = 0.002) predicted decreased PFS. RMH score ≥ 2 and MDACC score ≥ 3 were associated with decreased median OS (P = 0.029 and P = 0.031 respectively). It is feasible to conduct phase I studies in pediatric patients based on adult protocols. In the era of targeted therapy more trials should allow pediatric patients earlier in the drug development especially if deemed safe in adults in early phase trials. Most pharmaceutical industry sponsored trials exclude patients less than 18 years in phase I clinical trials. Even in the era of targeted therapy pediatric patients usually have to wait for most phases of trials to be completed in adults before being allowed to enroll in clinical trials of new therapies, even in the advanced metastatic and relapsed setting. Some investigator initiated phase 1 trials of combinations of US FDA approved agents allow patients less than 18 years. We report the preliminary analyses of the outcomes of pediatric patients enrolled in phase I studies initially designed for adults, but allowing for enrollment of patients under 18.

Highlights

Frontline and salvage cytotoxic chemotherapy regimens for pediatric cancers have become more complex and intensive in an effort to improve long-term cure rates. [1, 2] The intensification of treatment regimens has been facilitated by parallel improvements in supportive care, growth factor support, and intensive patient monitoring. [2] these more intensive frontline regimens may render patients more intolerant of subsequent treatments, including molecularly targeted therapies. (1) the intensive regimens may confer aggressiveness to the biology of the disease, making it more refractory to any form of therapy, even if the tumor harbors an actionable aberration.[3]
Even in the era of targeted therapy pediatric patients usually have to wait for most phases of trials to be completed in adults before being allowed to enroll in clinical trials of new therapies, even in the advanced metastatic and relapsed setting
We report the preliminary analyses of the outcomes of pediatric patients enrolled in phase I studies initially designed for adults, but allowing for enrollment of patients under 18

Summary

Introduction

Frontline and salvage cytotoxic chemotherapy regimens for pediatric cancers have become more complex and intensive in an effort to improve long-term cure rates. [1, 2] The intensification of treatment regimens has been facilitated by parallel improvements in supportive care, growth factor support, and intensive patient monitoring. [2] these more intensive frontline regimens may render patients more intolerant of subsequent treatments, including molecularly targeted therapies. (1) the intensive regimens may confer aggressiveness to the biology of the disease, making it more refractory to any form of therapy, even if the tumor harbors an actionable aberration.[3]. Frontline and salvage cytotoxic chemotherapy regimens for pediatric cancers have become more complex and intensive in an effort to improve long-term cure rates. [1, 2] The intensification of treatment regimens has been facilitated by parallel improvements in supportive care, growth factor support, and intensive patient monitoring. [2] these more intensive frontline regimens may render patients more intolerant of subsequent treatments, including molecularly targeted therapies. Phase I trials play a key role in the early evaluation of novel targeted therapies for patients with advanced cancer.[2, 4, 9, 12]. Children (patients ≤ 18 years of age) are not usually included on pharmaceutical industry sponsored Phase I trials

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