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At least 91 records · Page 5Linked to original sources

High-dose busulfan in patients with myeloma.

PURPOSE: To evaluate the use of high-dose busulfan (HDB) with autologous bone marrow transplantation (ABMT) in patients with myeloma. PATIENTS AND METHODS: Fifteen patients received HDB (16 mg/kg), eight of whom received high-dose melphalan (HDM) but had experienced a short remission or progression-free interval. Two patients had received HDM on two previous occasions, one had no response to low-dose melphalan, and four had impaired renal function (edathamil clearance < 40 mL/min). All patients received induction chemotherapy before HDB. RESULTS: Two patients were in complete remission (CR) after induction chemotherapy before HDB. Of the remaining 13 patients, four (31%) achieved CR and two (15%) achieved a partial remission for an overall response rate of 46%. There were three treatment-related deaths, but the toxicity was otherwise predictable and manageable. CONCLUSIONS: In heavily pretreated patients, HDB results in a relatively high response rate. It can also be used safely in patients with renal impairment who are not suitable for HDM.

Adult↗

Relationships between carboplatin exposure and tumor response and toxicity in patients with ovarian cancer.

PURPOSE: The study was undertaken to define the relationship between tumor response and carboplatin area under the curve (AUC) in patients with ovarian cancer; to study the relationship between carboplatin AUC and myelosuppression in the same population; to establish the true impact of carboplatin AUC, prior therapy, and pretreatment platelet and WBC counts on toxicity; and to define an optimal carboplatin exposure for treating patients with ovarian cancer. METHODS: With the equation AUC = dose/(glomerular filtration rate [GFR]+25), carboplatin AUC (course 1) was calculated for 1,028 patients (450 previously untreated) who received single-agent carboplatin (40 to 1,000 mg/m2) for advanced ovarian cancer. GFR was measured (chromium-51-edathamil [51Cr-EDTA] or creatinine clearance) in all patients. RESULTS: Regression analysis showed that carboplatin AUC, prior treatment, and Eastern Cooperative Oncology Group grade performance status (PS) are predictors of tumor response, thrombocytopenia, and leukopenia. Pretreatment platelet and WBC counts are additional predictors of thrombocytopenia and leukopenia, respectively. Although the likelihood of tumor response increased with increasing carboplatin AUC, this relationship was nonlinear. In all patient subsets, the likelihood of complete response (CR) or overall response did not increase significantly above a carboplatin AUC of 5 to 7 mg/mL x minutes. At any given carboplatin AUC, thrombocytopenia occurred more frequently than leukopenia, although both approached 100% as carboplatin AUC increased. Both thrombocytopenia and leukopenia were more frequent in pretreated than in untreated patients regardless of pretreatment count. At any carboplatin AUC, the influence of PS on likelihood of response and toxicity was profound. CONCLUSION: Carboplatin dosing by AUC will lead to more predictable toxicity, and increasing carboplatin AUC above 5 to 7 mg/mL x minutes does not improve the likelihood of response but does increase myelotoxicity. Therefore, careful evaluation of high-dose carboplatin therapy in a prospective, randomized trial is needed before such treatment becomes accepted practice.

Aged↗

Carboplatin pharmacokinetics in children: the development of a pediatric dosing formula. The United Kingdom Children's Cancer Study Group.

PURPOSE: The aim of this study was to define the pharmacokinetics of carboplatin in children and use the data to develop a pediatric dose formula. It was anticipated that renal function would be a major determinant of carboplatin disposition and the relationship between carboplatin clearance and glomerular filtration rate (GFR) was examined in detail. PATIENTS AND METHODS: Plasma carboplatin pharmacokinetics were measured as ultrafiltrable platinum in 22 patients (5 to 63 kg) following 200 to 1,000 mg/m2 of carboplatin. GFR was measured by the plasma clearance of chromium 51-edathamil (51Cr-EDTA). RESULTS: Carboplatin pharmacokinetics in children were best described in most patients (16 of 22) by a two-compartment model. The dose-normalized area under the plasma carboplatin concentration versus time curve (AUC) ranged from 3.1 to 9.6 mg/mL.min/400 mg/m2 and there was only a weak linear relationship between carboplatin dose and AUC (R2 = .31). There was a significant relationship between absolute carboplatin and 51Cr-EDTA clearances (R2 = .56), but the relationship was weaker (R2 = .28) when both clearances were normalized for body surface area. Carboplatin plasma clearance was predicted by the equation: clearance = GFR (mL/min) + 0.36 x body weight (BW; kg), and a modified form of the adult carboplatin dose formula is proposed: dose (mg) = target AUC x (GFR [mL/min] + [0.36 x BW(kg)]). Two further equations were developed that use the 51Cr-EDTA half-life (t1/2) to calculate the GFR and these may reduce errors resulting from inaccurate measurement of the volume of distribution for 51Cr-EDTA. In patients treated with single-agent carboplatin or carboplatin plus vincristine, there was a significant sigmoidal relationship between AUC and thrombocytopenia (R2 = .56). CONCLUSION: GFR-based carboplatin dosing in children should be feasible and will be evaluated prospectively.

Adolescent↗

[Lead poisoning in children].

Thirty children with lead intoxication were studied at the Hospital de Ninos Benjamin Bloom of San Salvador, during a period of eight years. Six cases were diagnosed retrospectively, whereas twenty-four were prospectively observed. Most of tham were between one to five years of age. The most common initial signs were related to the central nervous system and gastrointestinal tract. Mild and severe cases were treated with edathamil calcium disodium (Versanate), presenting successful outcome. A high incidence of muscular, neurological, bone and psychological sequels was observed. Preventive procedures and general management are emphasized.

Age Factors↗