A pilot study of high-dose carboplatin and pulsed etoposide in the treatment of childhood solid tumors.

Carboplatin was administered at 1,000 mg/m2/course in combination with etoposide at 300 mg/m2/course to 23 patients aged 5 months to 16 years. Five patients were affected by neuroblastoma, four by CNS tumors, three by Ewing's sarcoma, two by rhabdomyosarcoma, two by malignant teratoma, two by Wilms' tumor, two by head and neck carcinoma, one by hepatoblastoma, one by synovial sarcoma, and one by Langerhans-cell histiocytosis. Eleven patients were pretreated, seven of them with high-dose cisplatin. The overall response rate was 7/11 (64%) for pretreated and 10/12 (83%) for previously untreated patients. Myelosuppression was the main side effect, with anemia and thrombocytopenia more pronounced than leukopenia. Gastrointestinal toxicity and ototoxicity were very mild; nephrotoxicity and neurotoxicity other than hearing loss were not observed. In children with malignant tumors, the therapeutic activity of carboplatin at high doses, even in combination chemotherapy, deserves further studies

Occupational exposure to antiproliferative drugs in health care workers

[No abstract available

Chemotherapeutic agent cisplatin monitoring in biological fluids by means of inductively-coupled plasma emission spectrometry (ICP-AES).

The antitumoral agent cis-diamminedichloroplatinum (II) was administered at doses of 40 mg m-2 body surface area daily for 5 days via continuous i.v. infusion in association with etoposide (VP-16-213). The Pt concentration in serum up to 30 days from the beginning of the therapy was monitored by inductively-coupled plasma emission spectrometry. Results lead to two main conclusions: the analytical technique employed is suitable for measurements of Pt in biological fluids with the necessary precision (0.95-2.5%), accuracy (recovery 98.5-101.7%) and detection power (0.002-0.004 mg/l); there were effective Pt plasma concentrations for a greater length of time (with peak value 2.0 mg/l towards the end of treatment) than those achieved by other therapies so far adopted. On the other hand, toxic side effects, in particular gastrointestinal toxicity, myelosuppression and nephrotoxicity, were found to be not worse than those generally caused by the administration of the chemotherapeutic compound at lower doses. Both aspects were deeded to be essential prerequisites for better exploiting the drug's effectiveness

Cytomegalovirus infection in two infants with congenital or neonatal solid tumors

Two infants with fibrosarcoma and rhabdomyosarcoma diagnosed prenatally and at 2 months of age, respectively, and cytomegalovirus (CMV) infection are reported. Concomitant CMV infection was revealed by positive urine culture and/or CMV DNA, and CMV-specific IgM, IgA, and complement-fixing antibodies. The patients, showing very low levels of immune T cells, died at 3 and 8 months of age, respectively. A pathogenic role for CMV in the progression of the tumors is suggested

A PHARMACOKINETIC STUDY OF HIGH-DOSE CONTINUOUS INFUSION CISPLATIN IN CHILDREN WITH SOLID TUMORS

The pharmacokinetics of cisplatin were investigated in 14 patients, aged 10 months through 13 years who were affected by solid malignant tumors. High-dose cisplatin (40 mg/m2/d) was administered with repeated courses for five days as a continuous intravenous (IV) infusion. Total platinum (Pt) levels in plasma and urine and free (protein-unbound) Pt levels in plasma ultrafiltrate were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES). Areas under the concentration v time curve (AUCs) for mean total and free Pt levels were calculated for the 120-hour period of infusion and for the 384 and 120 hours following its completion, respectively. Half-lives of total and free Pt in plasma were calculated for the 216 hours following completion of infusion in five patients at their first course. The fraction of the administered Pt dose excreted in urine as Pt was determined for the five-day period of infusion and seven-day period after its completion. A total of 36 courses were studied. Maximum average Pt levels were reached after 120 hours of infusion: at the first course, 3.22 and 0.17 μg/mL for total and free Pt, respectively. Platinum levels declined according to a biexponential model, with initial half-lives of 18.3 and 16.9 minutes, and terminal half-lives of 81.9 and 59.0 hours as determined for total and free Pt, respectively. In the second and third courses studied there was a progressive increase in mean Pt plasma levels. Consequently, the free drug exposure as measured by AUC increased in all patients with repeated courses: 47.7% for the second and 124.4% for the third course, when compared with the first. At the same time, the mean fraction of the dose excreted in the urine for the 12-day period considered, was 44.1% for the first course, 36.2% for the second, and 28.4% for the third. The progressive enhancement of tissue exposure to the free cytotoxic drug, resulting from a reduced renal clearance of Pt with sequential courses of cisplatin, produced mainly increased toxicity while therapeutic effect progressively diminished