Phase II study of gemcitabine in children with solid tumors of mesenchymal and embryonic origin

Abstract

The therapeutic benefit and side-effect profile of gemcitabine in adults with relapsed solid tumors is well known. So far, few data are available about its significance in pediatric relapsed solid tumors. To determine the efficacy and tolerability of gemcitabine in children, the drug was administered by intravenous short-term infusion over 30 min at a dose of 1200 mg/m2 weekly for 3 weeks as one cycle in children with relapsed solid tumor of embryonic or mesenchymal origin. From May 2003 to September 2004, 14 male and six female patients (2-23, median 15.8 years) were recruited for this prospective open-label phase II study (two-step Simon design). The patients suffered from rhabdomyosarcoma (n=8), Ewing's sarcoma (n=4), osteosarcoma (n=2), neuroblastoma (n=3), hepatoblastoma (n=2) and nephroblastoma (n=1). Median duration of therapy was 27.5 days (7-99), corresponding to 4.0 (2-11) infusions of gemcitabine. Two patients (neuroblastoma and Ewing) had stable disease documented for 69 and 70 days, whereas no objective responses were observed. In 34/94 administered infusions; doses had to be reduced or omitted for grade 3-4 hematotoxicity. Minimal activity was observed in this cohort of children with a wide spectrum of mesenchymal and embryonic tumors. Given the relatively low dose of gemcitabine administered, this study does not exclude the possibility of activity at higher doses. Secondly, the tolerability of gemcitabine in children was consistent with that expected in adults. For further studies in this population, we recommend the use of gemcitabine in combination with other agents.

Enhanced anticancer effect of gemcitabine by genistein in osteosarcoma: the role of Akt and nuclear factor-κB

“…On the basis of this evidence, we suggest that gemcitabine may be a novel anticancer agent for OS. However, several clinical trials indicated that the effect of gemcitabine alone was disappointing [9,10]; this may be connected with drug resistance. Many anticancer agents, including gemcitabine, induce nuclear factor-kB (NF-kB) nuclear translocation and activation of its target genes, which impinge on cellular resistance to anticancer agents [11].…”

Gemcitabine and Docetaxel in Metastatic Sarcoma: Past, Present, and Future

“…These have generally involved gemcitabine with the U.S. Food and Drug Administration-approved bolus schedule, and have shown only low response rates [20,[22][23][24][25][26][27][28][29][30][31] (Table 1). Collectively, it is clear that uterine leiomyosarcoma is more sensitive to gemcitabine than other histologies and even leiomyosarcomas from other sites, and that other histologies can occasionally respond as well.…”

Implementing Good Clinical Practice in Two Noncommercial Phase II Studies in Children with Cancer

“…Unfortunately, both trials had to be stopped earlier than expected [5,6]. Still, aiming to contribute to a potential expansion of labelling meant to observe GCP.…”

“…However, the challenge is to cooperate with the authorities to explore the scope of the EU Regulations to apply them effectively and in a useful manner, so that there will be better quality and increased evidence rather than less progress [4]. The Coordination Center for Clinical Trials (KKS) of the University Hospital of Münster conducted two prospective open-label multicenter phase II studies of gemcitabine in children with relapsed malignancies [5,6]. Gemcitabine is a well-known drug in adults, and its therapeutic benefit and excellent side effect profile have been evidenced in relapse situations.…”