Vita Ridola

Long-Term Evaluation of Ifosfamide-Related Nephrotoxicity in Children

PURPOSE Ifosfamide is widely used in pediatric oncology but its nephrotoxicity may become a significant issue in survivors. This study is aimed at evaluating the incidence of late renal toxicity of ifosfamide and its risk factors. PATIENTS AND METHODS Of the 183 patients prospectively investigated for renal function, 77 treated for rhabdomyosarcoma, 39 for other soft tissue sarcoma, 39 for Ewings sarcoma, and 28 for osteosarcoma were investigated at least 5 years after treatment. No patients had received cisplatin and/or carboplatin. Glomerular and tubular functions were graded according to the Skinner system. RESULTS The median dose of ifosfamide was 54 g/m(2) (range, 18 to 117 g/m(2)). After a median follow-up of 10 years, 89.5% of patients had normal tubular function, and 78.5% had normal glomerular function rate (GFR). Serum bicarbonate and calcium were normal in all patients. Hypomagnesemia was observed in 1.2% and hypophosphatemia in 1%. The tubular threshold for phosphate was reduced in 24% of the patients (grade 1 in 15%, grade 2 in 8%, and grade 3 in 0.5%). Glycosuria was detected in 37% of the patients but was more than 0.5 g/24 hours in only 5%. Proteinuria was observed in 12%. Ifosfamide dose and interval from therapy to investigations were predictors of tubulopathy in univariate and multivariate analysis. In a multivariate analysis, an older age at diagnosis and the length of interval since treatment had independent impacts on the risk of abnormal GFR. CONCLUSION Renal toxicity is moderate with a moderate dose of ifosfamide. However, since it can be permanent and can get worse with time, repeated long-term evaluations are important, and this risk should be balanced against efficacy.

Testicular function of survivors of childhood cancer: a comparative study between ifosfamide- and cyclophosphamide-based regimens.

PURPOSE This study aimed at comparing gonadal toxicity of ifosfamide versus cyclophosphamide received during childhood. METHODS The evaluation was based on basal FSH measurement. LH and testosterone were also measured in most of the patients. One hundred patients had received ifosfamide and 59 had received cyclophosphamide. RESULTS Median age at treatment was 11.2 years. The median interval since treatment was 10.7 years (range 4.1-20.2) and median age at evaluation was 21.4 years (17.5-36.1). The median dose of ifosfamide and of cyclophosphamide was 54 g/m(2) (18-114) and 8.3 g/m(2) (4.6-22), respectively. All but two males had normal testosterone levels. FSH was abnormal in 28/59 patients (47.5%) after receiving cyclophosphamide and was within the normal range in 94/100 patients (94%) after receiving ifosfamide. CONCLUSIONS These results show that ifosfamide is associated with a lower risk of gonadal damage than cyclophosphamide. The risk of abnormal FSH increased with the cumulative dose of cyclophosphamide.

High-dose chemotherapy with autologous stem cell rescue followed by posterior fossa irradiation for local medulloblastoma recurrence or progression after conventional chemotherapy.

The objective of the current study was to determine the outcome of children with local recurrence or progression of medulloblastoma in patients who received high‐dose chemotherapy (HDC) and posterior fossa (PF) irradiation.

Medulloblastoma in young children

In early childhood medulloblastoma, three distinct treatment strategies are currently used by different national groups to improve survival rates and to delay or avoid craniospinal radiotherapy: (1) systemic chemotherapy and high‐dose chemotherapy, followed by radiotherapy at relapse; (2) systemic and intraventricular chemotherapy; (3) systemic chemotherapy and local conformal radiotherapy. A role for high‐dose chemotherapy to delay or avoid craniospinal radiotherapy as a part of multimodal treatment strategies, especially in young children with metastatic or postoperative residual disease, has been recognized by different co‐operative groups. Clinical and histological factors such as nodular‐desmoplastic variants are considered as important prognostic factors for risk‐adapted treatment recommendations. Pediatr Blood Cancer 2010;54:635–637.

Severe acute hypertriglyceridemia during acute lymphoblastic leukemia induction successfully treated with plasmapheresis

Children suffering from Acute Lymphoblastic Leukaemia (ALL) treated with asparaginase and corticosteroids are at risk of developing severe lipid abnormalities. The authors report the case of a 10‐year‐old male with extremely high plasma triglyceride concentrations (4,000 mg/dl) during the induction phase of ALL associated with mild pancreatitis. Hypertriglyceridemia was successfully managed with plasmapheresis with a decrease in triglyceride levels to 590 mg/dl. Apheresis appears to be safe and effective in reducing hypertriglyceridemia and preventing related complications. Pediatr Blood Cancer 2008;50:378–380.

Successful treatment with oral valganciclovir in immunocompetent infant with gastrointestinal manifestations of cytomegalovirus infection

A 3-month-old male infant was admitted to hospital with anemia. Follow-up controls revealed the presence of specific cytomegalovirus (CMV) antibodies. Virus was isolated from urine, blood, and saliva. At 7 months of age, he presented with melena. Polymerase chain reaction (PCR) of biopsy samples from the duodenum was positive for CMV. Anemia resolved after starting antiviral therapy with oral valganciclovir.

Anthracycline-related cardiotoxicity: risk factors and therapeutic options in childhood cancers

Anthracyclines play an important role in chemotherapeutic regimens for a wide spectrum of childhood tumors, but they can cause cytotoxic damage to cardiac cells, especially in combination with radiotherapy. Furthermore, cardiotoxicity increases with the cumulative dose and may lead to congestive heart failure and cardiomyopathy. Other factors, including age, pre-existing cardiac disease, length of follow-up, gender, route of administration, concomitant exposure to some chemotherapeutic drugs, trisomy 21 and black race, play a role in increasing the risk of cardiac dysfunction. The prevention of anthracycline-induced cardiotoxicity is mandatory as children are expected to survive for decades after being cured of their cancer. The purpose of this work is to point out the major risk factors of cardiotoxicity in children and to summarize some strategies to limit or prevent this complication and to treat the development of acute heart failure.

Anthracycline cardiotoxicity in childhood

Over the last 40 years, a significant advance has been made in the treatment of childhood and adult cancers. However, the increase of the survival rate points out medium-and long-term adverse effects that constitute a serious limitation for the quality of life in adults survived from a childhood cancer. Cardiovascular disease is an important cause of morbidity and mortality in adults treated with chemo-and radiotherapy for childhood cancers. Although some antitumor treatments are potentially cardiotoxic, anthracycline therapy and radiotherapy are mostly responsable for long-term cardiac damage. Anthracycline toxicity is generally limited to the myocardium, while radiation can cause injury to all components of the heart. The purpose of this review is to discuss the mechanisms of action of anthracyclines, their cardiotoxicity, the feasibility of screening, and the prevention of cardiac damage after treatment in childhood.

Temozolomide is an active agent in children with recurrent medulloblastoma/primitive neuroectodermal tumor: an Italian multi-institutional phase II trial

BACKGROUND The aim of this study was to assess the objective response rate (ORR) of children and young adults with recurrent medulloblastoma/primitive neuroectodermal tumor (MB/PNET) treated with temozolomide (TMZ). The secondary purpose was to analyze the toxicity profile of TMZ when administered orally for 5 days in 3 divided daily doses every 28 days. METHODS Forty-two patients with recurrent MB/PNET, aged 21 years and younger, were recruited. Patients were treated with oral TMZ. Starting doses ranged from 120 to 200 mg/m(2)/day based on previous treatments. A craniospinal MRI was performed prior to the first cycle of TMZ and following every 2 cycles of treatment. RESULTS Median age was 10 years (range, 2-21 years). Forty of 42 patients were assessed for response and toxicity. The objective response rate was 42.5%: 6 patients achieved a complete response, 11 had a partial response, and 10 had stable disease. Progression-free survival rates for all patients at 6 and 12 months were 30% and 7.5%, respectively. Their median overall survival rates at 6 and 12 months were 42.5% and 17.5%, respectively. No major extrahematological effects or life-threatening events were reported. The most common grade 3/4 toxicity included thrombocytopenia (17.5%), neutropenia (7.5%), and anemia (2.5%). CONCLUSIONS TMZ proved to be an effective agent in children and young adults with MB/PNET, heavily pre-treated, with a tolerable toxicity profile.

Efficacy and safety of transdermal buprenorphine in the management of children with cancer-related pain

The current study investigated the efficacy, safety, tolerability, and compliance of a transdermal buprenorphine delivery system for the management of chronic cancer pain in the pediatric population.