Budotitane [cis-diethoxybis(1-phenylbutane-1,3-dionato)titanium (IV)] is a novel inorganic metal complex. Preclinical studies in established screening models indicate considerable antitumor activity. We have performed a clinical Phase I and pharmacokinetic trial with budotitane administered as i.v. infusion twice weekly. The starting dose of 100 mg/m2 was derived from a prior single dose Phase I study. Eighteen patients with solid tumors refractory to all other known treatment modalities were entered. 17 patients had received prior chemotherapy. Dose levels ranged from 100 mg/m2 to 230 mg/m2, with a total of 122 budotitane infusions administered. Neither leuko- nor thrombocytopenia were observed. 2/5 pts at 180 mg/m2 and 2/4 pts at 230 mg/m2 developed a 3-fold increase of reticulocytes without signs of hemolysis or bleeding. Nonhematologic toxicity was moderate at doses of < or = 180 mg/m2. Fifteen patients reported loss of taste at the day of infusion. At 230 mg/m2, 2/4 pts developed WHO grade 3 cardiac arrhythmias with polytope premature ventricular beats and nonsustained ventricular tachycardia. A limited pharmacokinetic analysis was performed at dose levels 180 mg/m2 and 230 mg/m2. At 180 mg/m2, Cmax was 2.9 +/- 1.2 microg/ml, t1/2 78.7 +/- 24.4 h, Cltot 25.3 +/- 4.6 ml/min and AUC 203 +/- 71.5 h x microg/ml. At 230 mg/m2, Cmax was 2.2 +/- 0.8 microg/ml, t1/2 59.3 +/- 12.1 h, Cltot 44.9 +/- 23.6 ml/min and AUC was 183 +/- 90.4 h x microg/ml. No objective tumor response was observed. We conclude that the maximum tolerated dose of budotitane administered twice weekly is 230 mg/m2, the dose limiting toxicity is cardiac arrhythmia. Further evaluation of the nature of the cardiac toxicities observed is warranted. Using this schedule, 180 mg/m2 is a safe dose for subsequent clinical studies.

Cancer-related fatigue is the most disabling symptom experienced by breast cancer patients following the cancer treatment. The positive effects of physical activity in the rehabilitation of breast cancer patients are documented in several studies. In a randomized controlled study the effects of a structured physical training program on fatigue and health-related quality of life were evaluated. Patients and Methods: 63 breast cancer patients with cancer-related chronic fatigue were randomized at the beginning of the inpatient rehabilitation. The control group received the standard complex rehabilitation program, the intervention group a structured physical training program and additional muscle strength and aerobic exercises. The effects of the treatment were evaluated by questionnaires at the start of rehabilitation (t1), end of rehabilitation (t2), and 3 months after t2 (t3). Isometric muscle strength and aerobic capacity were evaluated at t1 and t2. Results: There was an improvement of muscle strength at the end of rehabilitation for both groups. The increase from t1 to t2 was significantly higher for the training group. The scores for global quality of life, physical well-being, and functionality increased from t1 to t2, but further improvement in the follow-up (t3) was only observed in the training group. The cancer-related fatigue was significantly reduced in the training group from t1 to t3, however, not in the control group. Conclusions: Structured physical training programs initiated during inpatient rehabilitation and continuously practiced in the time thereafter can improve symptoms of chronic fatigue and quality of life in breast cancer patients.

Tumor necrosis factor (TNF) is a cytokine produced in vivo by activated macrophages and monocytes with pleiotropic effects on normal and malignant cells. TNF is cytotoxic to several tumor cell lines in vitro and in vivo. Phase I and phase II trials have been conducted to determine toxicity to humans and to evaluate responses. Recent investigations will be reviewed. Despite promising results in vitro and in vivo, data from systemic administration in the treatment of malignancies have been disappointing. Local administration has been successful. Therefore, we suggest that future efforts concerning TNF administration in the treatment of malignancies should aim at local treatment.

The purpose of this paper was to define the histologic distrito the endemic (African) and sporadic forms of Burkitt lymbution, clinical features, and treatment response of childhood phoma, which differ in their clinical presentation, regional non-Hodgkin lymphoma (NHL) in northeastern Brazil. We incidence, association with Epstein-Barr virus, and biologic Patients and methodsThere was a striking predominance of the small noncleaved cell (Burkitt) subtype, which occurred in 92 of the 98 children and adolescents diagnosed with NHL. Subsequent analyses Between January 1980 and October 1987, a total of 98 chilfocused on these patients. The majority (n = 84) had advanced dren were diagnosed with non-Hodgkin lymphoma at the parental refusal/abandonment of therapy (10%). Epstein-BarrDiagnostic imaging studies were performed as indicated. virus (EBV) was detected in tumor cells from eight of the 11The pathologic diagnosis was established by histologic Of the 98 patients evaluated during the study period, 92 had small noncleaved cell histology. There were only five cases of lymphoblastic lymphoma and one of large cell histology. Having confirmed the predominance of Burkitt lymIntroduction phoma among the pediatric patients with NHL, we then focused on these 92 cases. Records were reviewed to evaluate The non-Hodgkin lymphomas of childhood are predominantly clinical and biological features, type of treatment, and outhigh-grade extranodal tumors that include the lymphoblastic, come. When sufficient paraffin-embedded tumor tissue was large cell, and small noncleaved cell subtypes. 1 The relative available, in situ RNA/RNA cytohybridization using plasmids frequency of these subtypes varies with geographic location.containing EBV-encoded small nuclear RNA was performed In the United States, the distribution is almost equal, 2 whereas at St Jude Children's Research Hospital to detect the presence small noncleaved cell tumors (Burkitt lymphoma) account for of Epstein-Barr virus DNA. 6 In these cases, the histologic diagthe majority of childhood NHLs in equatorial Africa. 3,4 In nosis was also reviewed and confirmed by a pediatric hematonortheastern Brazil -an area in which we have established a pathologist at St Jude (CWB). cooperative clinical program -anecdotal evidence suggests an increased overall incidence of lymphoma. However, to our knowledge, there have been no reports focusing on pediatric Hodgkin or non-Hodgkin lymphomas in this region. TreatmentWe noted an apparent predominance of the small noncleaved cell histology among children treated for NHL at a There were two distinct treatment periods. From 1980 to major pediatric cancer center in Recife, Brazil. In the present 1983, all consenting patients were treated with induction study, we evaluated the accuracy of this clinical impression chemotherapy similar to that used in the LSA 2 L 2 regimen and assessed long-term treatment outcome. We also sought to described by Wollner et al, 7 followed by maintenance therapy determine the relationship of the small noncleaved...