N7: a novel multi-modality therapy of high risk neuroblastoma (NB) in children diagnosed over 1 year of age.

BACKGROUND: The N7 protocol for poor-risk neuroblastoma uses dose-intensive chemotherapy (as in N6 protocol [Kushner et al.: J Clin Oncol 12:2607-2613, 1994] but with lower dosing of vincristine) for induction, surgical resection and 2100 cGy hyperfractionated radiotherapy for local control, and for consolidation, targeted radioimmunotherapy with 131I-labeled anti-GD2 3F8 monoclonal antibody and immunotherapy with unlabeled/unmodified 3F8 (400 mg/m2). PROCEDURE: The chemotherapy consists of: cyclophosphamide 70 mg/kg/d x 2 and a 72-hr infusion of doxorubicin 75 mg/m2 plus vincristine 2 mg/m2, for courses 1, 2, 4, and 6; and cisplatin 50 mg/m2/d x 4 and etoposide 200 mg/m2/d x 3, for courses 3, 5, and 7. 131I-3F8 is dosed at 20 mCi/kg, which is myeloablative and therefore necessitates stem-cell support. RESULTS: Of the first 24 consecutive previously untreated patients more than 1 year old at diagnosis, 22 were stage 4 and two were unresectable stage 3 with MYCN amplification. Chemotherapy achieved CR/VGPR in 21 of 24 patients. Twenty patients to date have completed treatment with 131I-3F8, and 15 patients have completed all treatment. With a median follow-up of 19 months, 18 of 24 patients remain progression-free. CONCLUSIONS: Major toxicities were grade 4 myelosuppression and mucositis during chemotherapy, and self-limited pain and urticaria during antibody treatment. Late effects include hearing deficits and hypothyroidism.

Targeted radioimmunotherapy for leptomeningeal cancer using (131)I-3F8.

BACKGROUND: Intrathecal antibody-based targeted therapies may have clinical potential for patients with leptomeningeal (LM) cancer. PROCEDURE: Five patients with GD2-positive LM tumors were injected with 1-2 mCi intra-Ommaya (131)I-3F8, a murine IgG3 antibody specific for GD2. Serial cerebrospinal fluid (CSF) and serum samples and SPECT imagings (4, 24, and 48 hr) were performed to predict radiation doses to the tumor and normal brain and blood prior to the administration of larger therapeutic doses. RESULTS: Side effects included self-limited fever, headache, and vomiting. Focal (131)I-3F8 uptake consistent with tumors was seen along the craniospinal axis in four patients. Calculated radiation dose to the CSF was 14.9-56 cGy/mCi and to blood and other organs outside the CNS less than 2 cGy/mCi. CONCLUSIONS: Intraventricular (131)I-3F8 successfully detected LM disease and resulted in a large favorable CSF/blood ratio. Intraventricular (131)I-3F8 may have clinical utility in the diagnosis and radioimmunotherapy of GD2-positive LM cancers. Med. Pediatr. Oncol. 35:716-718. 2000.

Arterial, peritoneal, and intraventricular access devices.

OBJECTIVE: To provide an overview of access devices used to treat cancers through the arterial, peritoneal, and intraventricular body systems. CONCLUSIONS: Short-term and long-term devices have been developed over the last 35 years for cancer treatment. Although less amenable to standard methods of therapy, the various access devices available to access the arterial, peritoneal, and intraventricular systems have provided a safe and reliable means for drug therapy. Access devices assist in delivering high concentrations of drugs directly to the center of the tumor. Complications and toxicities are inherent with these devices from the drug therapy as well as the device. Nursing assessment can provide early identification of potential problems and implementation of appropriate interventions. IMPLICATIONS FOR NURSING PRACTICE: As the availability of these devices increases, so must the nurse's knowledge base to provide optimal safe care. Oncology nurses are challenged to know the differences between the devices, the device of choice for the individual patient, insertion procedures, and maintenance protocols.

Pharmacokinetics of ara-C and ara-U in plasma and CSF after high-dose administration of cytosine arabinoside.

Cytosine arabinoside (ara-C) and uracil arabinoside (ara-U) levels were measured in the plasma, cerebrospinal fluid (CSF), and urine of 10 patients exhibiting primary central nervous system lymphoma who received 31 infusions of high-dose ara-C (3 g/m2) as part of their treatment regimen. Peak plasma and CSF ara-C levels were 10.8 and 1.5 micrograms/ml, respectively. Ara-C was cleared more rapidly from plasma than from CSF. Ara-U appeared rapidly in both plasma and CSF, reaching a peak that was 10 times higher than the corresponding ara-C concentration (104 and 11.2 micrograms/ml, respectively). Only 4%-6% of the dose was excreted unchanged in the urine, but 63%-73% of it appeared as ara-U within the first 24 h. The presence of leptomeningeal lymphoma did not affect the CSF level of ara-C or ara-U.

Phase I and clinical pharmacological study of 4-demethoxydaunorubicin (idarubicin) in children with advanced cancer.

We conducted a phase I and pharmacokinetic study of i.v. idarubicin, a new anthracycline analogue, in 42 evaluable children 1-19 years old. Twenty-seven had leukemia and 15 had various solid tumors. The drug was administered in escalating doses of 10 to 40 mg/m2/course in 3 equal fractions over 3 consecutive days at 14- to 21-day intervals. Myelosuppression and mucositis were the limiting toxicities for short-term administration. Nausea, vomiting, and elevation of liver enzymes and bilirubin were the other toxicities encountered. Peak toxicity occurred 2 weeks after drug administration with median recovery by day 24. All but 4 patients with solid tumors had prior anthracyclines. Mild cardiac function changes without clinical symptoms were observed in 17 of 35 patients measured by serial cardiac evaluations. In addition, there were 4 patients with congestive heart failure. On postmortem examination, 4 patients had changes consistent with anthracycline cardiomyopathy at a prior median total anthracycline dose of 175 mg/m2. The maximum tolerated dose for patients with solid tumors was 15 mg/m2 course in 3 divided doses. Patients with leukemia tolerated 30 mg/m2/course. Six of 15 evaluable patients with acute lymphoblastic leukemia who received greater than or equal to 30 mg/m2 idarubicin achieved a remission (M1 marrow status). The plasma clearance of idarubicin fits a 3-compartment model with a harmonic mean half-life of 2.4 min, 0.6 h, and 11.3 h for alpha, beta, and gamma phases, respectively. Idarubicinol was the only metabolite detected in the plasma and it accumulated during the 3 days of therapy. Idarubicin is similar to daunorubicin in pharmacology and toxicity. While the cardiotoxic dose still must be delineated, the complete remission achieved in multiple relapsed patients with acute lymphoblastic leukemia indicate promising activity in at least that disease.