The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute myeloid leukemia in children: an evidence-based review.

Clinical research examining the role of hematopoietic stem cell transplantation (SCT) in the therapy of acute myeloid leukemia (AML) in children is presented and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the treatment recommendations. Treatment recommendations based on the evidence are presented in the table entitled "Summary of Treatment Recommendations Made by the Expert Panel for Pediatric Acute Myeloid Leukemia" and were reached unanimously by a panel of experts in AML. The identified priority areas of needed future research in pediatric AML include: What is the role of risk group stratification, including the role of cytogenetics, in selection of patients for allogeneic SCT, especially those in first CR? What is the appropriate timing and use of alternative donor SCT, given that matched unrelated donor SCT appears to yield outcomes equivalent to matched related donor SCT? What is the role of reduced intensity SCT (including the use of fludarabine-based preparative regimens) and/or other immunomodulatory approaches to maximize the graft-versus-leukemic effect? and What is the role of biologically targeted agents (ie, tyrosine kinase inhibitors, farnesyl transferase inhibitors, Flt-3 inhibitors, etc) in the treatment of AML, including induction, consolidation, conditioning regimens, and after SCT?

A phase I study of a weekly schedule of paclitaxel and carboplatin in patients with advanced carcinoma.

BACKGROUND: We conducted a Phase I study of weekly paclitaxel (P) and carboplatin (C) in patients with advanced malignancies to determine the maximum tolerated dose (MTD) of this combination. METHODS: Dose levels were escalated independently for patients with and without previous chemotherapy exposure and advanced malignancies. Both agents were administered weekly for 6 weeks followed by a 2-week break per cycle. P, escalated to tolerance starting at 135 mg/m(2) per week, and C, fixed dose at area under the curve (AUC) = 2 mg/mL/min, were administered to groups of three or six patients. Doses were modified for granulocyte counts less than 1800/microL or for neurotoxicity greater than Grade 1. MTD was defined as the highest dose level at which less than 50% of patients developed unacceptable toxicity and received more than 80% of the intended dose during the first cycle. Dose levels were escalated until these conditions were exceeded. RESULTS: Twenty-seven patients (12 patients with previous chemotherapy exposure and 15 chemotherapy-naive patients) were examined for toxicity. Dose escalation was halted due to neutropenia and/or Grade 2/3 neuropathy in both arms. The MTD was P = 135/C = 2 for patients with previous chemotherapy exposure and P = 150/C = 2 for chemotherapy-naive patients. CONCLUSIONS: The combination of P and C administered on a weekly schedule permits a two to threefold enhancement of P dose intensity with full doses of C. Phase II trials of this regimen in patients with various malignancies are being evaluated to determine efficacy and tolerance.

A multiinstitutional, concurrent chemoradiation trial of strontium-89, estramustine, and vinblastine for hormone refractory prostate carcinoma involving bone.

BACKGROUND: Estramustine phosphate (EMP) and vinblastine have radiosensitizing properties and significant activity against hormone refractory prostate carcinoma. Strontium-89 is a palliative agent that acts as a selective radiation source for bone metastasis. The combination of EMP, vinblastine, and strontium-89 was developed to exploit the potential for radiosynergy. PATIENTS AND METHODS Forty-four patients at the Brown Oncology Group affiliated hospitals were treated with oral EMP 600 mg/m2 daily on Weeks 1-4 and 7-10, vinblastine 4 mg/m2 intravenously once each week on Weeks 1-4 and 7-10, and strontium-89 2.2 MBq/kg on Day 1. Courses were repeated every 12 weeks. Response assessment was based on a change in the serum prostate specific antigen (PSA) levels, correlated with change in measurable disease and bone scan appearance. RESULTS: A greater than or equal to 50% decline in PSA for at least 6 weeks was observed in 21 patients (48%, 95% confidence interval, 33-62%). Median duration of response was 23 weeks (range, 6-70.8 weeks). The median survival was 13 months with 1- and 2-year survival rates of 55% and 25%, respectively. After completion of protocol therapy, a retrospective review showed that only nine patients received subsequent palliative external beam radiation after progression. CONCLUSIONS: The addition of strontium-89 to the regimen of EMP and vinblastine can be delivered safely and in repeated doses, provides effective palliation, and may decrease the need for future radiation therapy. A randomized trial is necessary to quantify these effects.