The in-vitro uptake of four anthracyclines into leukemic cells was investigated. The accumulation was found to be dependent on the extracellular anthracycline concentration in a linear fashion. The steady state intracellular drug level was reached very quickly and was found to be correlated to the extracellular pH-value in the range between 6.4 and 7.4. Intracellular anthracycline accumulation was restricted in a leukemic subline (F 4-6 R), which was found to be 86 times more resistant to doxorubicin compared with its wild tpye (F 4-6). The importance of the initial uptake phase of anthracyclines into leukemic cells raises the question whether long-term "cardioprotective" anthracycline application schedules will retain the same antileukemic effect as conventional bolus injection.

Animals↗

PubMedDate not supplied

[Retinoblastoma gene analysis in a patient with osteosarcoma following previous bilateral retinoblastoma].

In a native osteosarcoma specimen of a patient cured of a bilateral retinoblastoma eight years before we found a homozygous deletion of a 7.5 kb Hind III-fragment within the retinoblastoma gene and a hemizygous deletion of the same fragment in its constitutional cells. In a native osteosarcoma tissue of a lung metastasis of a patient with sporadic osteosarcoma the Rb-gene-analysis did not reveal any deletion within the gene. This might be due to the fact that the used c-DNA-probe did not detect point mutations. Nevertheless, the possibility of additional or alternative transforming events should be kept in mind.

Brain Neoplasms↗

PubMedDate not supplied

[The pharmacokinetics of doxorubicin].

Doxorubicin serum levels were measured with a highly specific reversed-phase HPLC-method in patients undergoing combination chemotherapy. Serum elimination kinetics of doxorubicin follow a bi- or triphasic first order pattern with a high interpatient variability. T 1/2 of the first distribution phase was 5.4 min. T 1/2 of the terminal steady-state elimination phase was 1273 min. After consecutive bolus application of 15 mg/m2 (4 times per 48 h) cumulation of doxorubicin was found in patient's serum. Serum levels 4 h after bolus injection of doxorubicin were found to be correlated with the area under the elimination curve. Therefore, 4 h serum levels after bolus injection can be used for clinical studies correlating pharmacokinetics with antineoplastic properties of doxorubicin.

Adolescent↗

PubMedDate not supplied

[Antineoplastic effectiveness and toxicity of idarubicin (4-demethoxy-daunorubicin) in recurrent acute leukemias in childhood].

11 patients with refractory acute leukemia of childhood were treated with idarubicin per os. Bone marrow toxicity which was observed at a dose level of 60 mg/m2 p.o. (3 x 20 mg q 24 hrs p.o.) per 3 weeks was found to be the dose limiting factor. In contrast to the first phase I study of Tan et al. (16) the maximal tolerated dose in the present study was found to be lower at a level of 90 mg/m2 p.o. (3 x 30 mg/m2 p.o. q 24 hrs) per 3 weeks. Therefore, we recommend a dosage of 60 mg/m2 p.o. (3 x 20 mg/m2 p.o. q 24 hrs) per 3 weeks as a starting dose for phase II/III studies. 2 out of the 11 anthracycline pretreated patients (91-880 mg/m2) with acute leukemia reached a complete remission undergoing idarubicin p.o. as a single therapy.

Adolescent↗

PubMedDate not supplied

[Cooperative osteosarcoma study COSS-77: results after 4 years].

71 patients with resectable osterosarcoma received chemotherapy for one year including high-dose methotrexate (18 x 200 mg/kg), adriamycin (5 x [2 x 45] mg/m2) and cyclophosphamide (6 x 1200 mg/m2). During the initial 15 weeks adriamycin was used preferentially and cytostatic agents were applied in a higher frequency than later on. 41/71 patients are continuously free of disease with a median follow up of 39 (24-54) months. The latest appearance of pulmonary metastases was observed at 28 months so far. 18/27 (67%) patients with extension of tumor lesion beyond 1/3 long bones length by x-ray examination relapsed in contrast to 12/43 (28%) patients with smaller lesions. 1 patient died from adriamycin induced cardiomyopathy. Generally therapy was well tolerated. An average of 70-80% of planned drug dosages could be realized without measurable influence of individual differences on outcome.

Adolescent↗

PubMedDate not supplied

[COALL-80 therapy in the management of acute lymphoblastic leukemia in childhood--an interim report].

In order to reduce the toxicity of the otherwise very effective childhood ALL treatment protocol BFM 76/79 asparaginase was omitted from the 4-drug induction regimen and placed as single drug before the intensification phase. In addition the effect of 3-monthly intermediate dose methotrexate (ID-MTX) pulses versus conventional vincristine (VCR) pulses during maintenance therapy was studied. Of 145 evaluable patients 124 (85.5%) survive in continuous and complete remission (CCR) at a median observation time of 21 (1,5-47) months. The expected rate of patients in CCR at 4 years is 75% respectively 80% after exclusion of 4 patients with fatal complications and one remission failure. These relapse free survival data re equal to the BFM 76/79 and 79/81 results. There was very few therapy related morbidity and no mortality from the COALL-80 induction therapy modification. The intensification phase, however, which was adopted from the BFM study without modification was difficult to manage and was not free of life threatening mostly infectious complications which were fatal in 4 cases. ID-MTX pulses did not prove superior to conventional VCR pulses. The relapse rate in patients with the c-ALL subtype was markedly lower than in any other subtype, remarkably also than in the undifferentiated type.

Adolescent↗