Landscape of early clinical trials for childhood and adolescence cancer in Spain

Purpose: Despite numerous advances, survival remains dismal for children and adolescents with poor prognosis cancers or those who relapse or are refractory to first line treatment. There is, therefore, a major unmet need for new drugs. Recent advances in the knowledge of molecular tumor biology open the door to more adapted therapies according to individual alterations. Promising results in the adult anticancer drug development have not yet been translated into clinical practice. We report the activity in early pediatric oncology trials in Spain. Methods: All members of the Spanish Society of Pediatric Hematology Oncology (SEHOP) were contacted to obtain information about early trials open in each center. Results: 22 phase I and II trials were open as of May 2015: 15 for solid tumors (68 %) and 7 for hematological malignancies (32 %). Fourteen (64 %) were industry sponsored. Since 2010, four centers have joined the Innovative Therapies For Children With Cancer, an international consortium whose aim is developing novel therapies for pediatric cancers. A substantial number of studies have opened in these 5 years, improving the portfolio of trials for children. Results of recently closed trials show the contribution of Spanish investigators, the introduction of molecularly targeted agents and their benefits. Conclusions: Clinical trials are the way to evaluate new drugs, avoiding the use of off-label drugs that carry significant risks. The Spanish pediatric oncology community through the SEHOP is committed to develop and participate in collaborative academic trials, to favor the advancement and optimization of existing therapies in pediatric cancer (AU)

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Landscape of early clinical trials for childhood and adolescence cancer in Spain.

PURPOSE: Despite numerous advances, survival remains dismal for children and adolescents with poor prognosis cancers or those who relapse or are refractory to first line treatment. There is, therefore, a major unmet need for new drugs. Recent advances in the knowledge of molecular tumor biology open the door to more adapted therapies according to individual alterations. Promising results in the adult anticancer drug development have not yet been translated into clinical practice. We report the activity in early pediatric oncology trials in Spain. METHODS: All members of the Spanish Society of Pediatric Hematology Oncology (SEHOP) were contacted to obtain information about early trials open in each center. RESULTS: 22 phase I and II trials were open as of May 2015: 15 for solid tumors (68 %) and 7 for hematological malignancies (32 %). Fourteen (64 %) were industry sponsored. Since 2010, four centers have joined the Innovative Therapies For Children With Cancer, an international consortium whose aim is developing novel therapies for pediatric cancers. A substantial number of studies have opened in these 5 years, improving the portfolio of trials for children. Results of recently closed trials show the contribution of Spanish investigators, the introduction of molecularly targeted agents and their benefits. CONCLUSIONS: Clinical trials are the way to evaluate new drugs, avoiding the use of off-label drugs that carry significant risks. The Spanish pediatric oncology community through the SEHOP is committed to develop and participate in collaborative academic trials, to favor the advancement and optimization of existing therapies in pediatric cancer.

Efficacy and safety of liposomal cytarabine in children with primary CNS tumours with leptomeningeal involvement.

PURPOSE: To assess the efficacy and safety of liposomal cytarabine in the treatment of de novo and relapsed leptomeningeal involvement in children with primary CNS tumours. METHODS: Data from clinical charts were entered into a database for consecutive unselected patients (n=20) from nine Spanish centres. Diagnosis of leptomeningeal involvement was confirmed by cytology, MRI and/or CT scan. The dose of liposomal cytarabine used varied from 20 to 50 mg, by age. RESULTS: There were 8 females and 12 males, mean age 7.3 years (range 8 months to 18 years). The tumours were: 10 medulloblastomas, 4 ependymomas, 3 primitive neuroectodermal tumours and 3 other tumours. Fourteen had undergone previous chemotherapy and 12 radiotherapy. Nine received concurrent chemotherapy and 2 concurrent radiotherapy. Median follow-up was 244.5 days (range 12- 869). Patients received a median of 5 doses (range 1-9) of liposomal cytarabine. A neurological response (complete or partial) was seen in 11/19 (58%) and a cytological response in 7/10 (64%). Median time to neurological progression exceeded 180 days (range 12-869). Adverse effects were reported in 11/20 patients, but none was grade IV. DISCUSSION: Liposomal cytarabine was well tolerated and efficacious in this patient group, but prospective randomised trials are needed.

Efficacy and safety of liposomal cytarabine in children with primary CNS tumours with leptomeningeal involvement

PURPOSE: To assess the efficacy and safety of liposomal cytarabine in the treatment of de novo and relapsed leptomeningeal involvement in children with primary CNS tumours. METHODS: Data from clinical charts were entered into a database for consecutive unselected patients (n=20) from nine Spanish centres. Diagnosis of leptomeningeal involvement was confirmed by cytology, MRI and/or CT scan. The dose of liposomal cytarabine used varied from 20 to 50 mg, by age. RESULTS: There were 8 females and 12 males, mean age 7.3 years (range 8 months to 18 years). The tumours were: 10 medulloblastomas, 4 ependymomas, 3 primitive neuroectodermal tumours and 3 other tumours. Fourteen had undergone previous chemotherapy and 12 radiotherapy. Nine received concurrent chemotherapy and 2 concurrent radiotherapy. Median follow-up was 244.5 days (range 12- 869). Patients received a median of 5 doses (range 1-9) of liposomal cytarabine. A neurological response (complete or partial) was seen in 11/19 (58%) and a cytological response in 7/10 (64%). Median time to neurological progression exceeded 180 days (range 12-869). Adverse effects were reported in 11/20 patients, but none was grade IV. DISCUSSION: Liposomal cytarabine was well tolerated and efficacious in this patient group, but prospective randomised trials are needed (AU)

Topotecan asociado a ciclofosfamida como tratamiento de tumores sólidos pediátricos avanzados / Topotecan associated to cyclophosphamide as treatment of advanced pediatric solid tumors

Se presenta un estudio retrospectivo de la utilización de topotecan y ciclofosfamida como terapia de rescate en niños con tumores solidos refractarios ó recidivados que habían recibido previamente terapia intensiva, incluyendo en dos de ellos megaterapia con rescate hematopoyetico. Se incluyeron 19 pacientes (seis sarcomas de partes blandas, cuatro neuroblastomas, tres sarcomas de Ewing, tres tumores neuroectodermicos primitivos, dos retinoblastomas bilaterales y un meduloblastoma. La dosis total por ciclo fue de 1.250 mg de ciclofosfamida y 3,75 mg de topotecan. Los ciclos se repitieron cada 28 días. Se administraron un total de 79 ciclos. Se observaron 3 remisiones completas (dos rabdomiosarcomas y un sarcoma sinivial) y 6 remisiones parciales (dos neuroblastomas, un meduloblastoma, un retinoblastoma y un tumor desmoplasico) lo que significa un 47 por ciento de casos con respuesta objetiva al tratamiento. La principal toxicidad observada fue la mielosupresion (tras el 20 por ciento de los ciclos) (AU)

Wilms' tumours with intracaval involvement.

Since Gross established the basic rules for nephrectomy in Wilms' tumour (WT) in 1953, the management of nephroblastoma has been more straightforward. However, some cases with intravascular involvement, currently detected by ultrasound (US), may represent a daunting challenge for the surgeon. Inferior vena cava with tumour thrombus, induced by WT, can be asymptomatic and, if undetected, can contribute to poorer prognosis for two main reasons: possible neoplastic cells inside the thrombus and higher morbidity risk of surgery. From 1979 to 1993, 81 WT were studied by routine US. Intracaval thrombosis was diagnosed in four (5%), in one of which the thrombus extended to the right atrium. In our experience, the surgical strategy in each of the four cases (100% survival) depended on the length of the thrombus and whether or not it infiltrated the vena cava wall. If the thrombus can be easily removed: complete resection. However, in cases of atrial thrombus, and more particularly if the thrombus involves the intima, we suggest the thrombus not be touched since the problem may be solved by preoperative and postoperative chemotherapy. Thus the favourable prognosis would be maintained and superfluous risky surgery avoided.